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V M Edwards

Publications and source records attributed to V M Edwards.

At least 19 recordsLinked to original sources
PubMed2000

Maternal serum screening for trisomy 18: assessing different statistical models to optimize detection rates.

We have evaluated three alternative models for trisomy 18 screening using the maternal serum markers alpha-fetoprotein (AFP) and intact human chorionic gonadotrophin (hCG). Using data from 46 affected pregnancies and 48 150 unaffected pregnancies, we calculated distribution parameters for AFP and hCG multiples of the median (MoMs) and the factor comprising AFP MoMxhCG MoM. The trisomy 18 risk at mid-trimester was then calculated using either bivariate analysis of AFP and hCG MoMs or univariate analysis of AFP MoMxhCG MoM. The observed detection rates and positive rates obtained using either published distribution parameters or those derived from the West Midlands population were compared for each model. Using fixed cut-offs for AFP and hCG of 0.66 and 0.40 MoMs resulted in a detection rate of 28.3% for a 0.5% false positive rate (FPR). Using published parameters, the univariate analysis model had a slightly higher detection rate of 32.6% for a 0.5% FPR (cut-off 1:248) compared to the bivariate model which was 28.3% (cut-off 1:239). Locally derived distribution parameters significantly improved the detection rate for the bivariate model for FPRs between 0.4-1.3% but worsened it below 0.4%. For the univariate model there was little difference in detection whether local or published parameters were used. Thus, we have confirmed that trisomy 18 screening using two markers can be a worthwhile addition to Down screening.

Chorionic Gonadotropin↗
PubMed1999

Evaluation of different weight correction methods for antenatal serum screening using data from two multi-centre programmes.

Weight correction of serum markers is widely used when screening for Down's syndrome and open neural tube defects (NTD) because marker concentrations decrease with increasing maternal weight. Log-linear regression is frequently used for determining weight correction factors, but recently reciprocal-linear regression has been suggested to have advantages. We compared both methods of weight correction using data from two screening programmes carried out by this laboratory, one using alpha-fetoprotein (AFP) and total human chorionic gonadotrophin (HCG) (n = 129,143) and the other, AFP and free beta-HCG (n = 39,982). The reciprocal-linear method fitted the data more closely but did not significantly alter the detection rate or screen positive rate (SPR) for Down's syndrome or NTD with either dataset. Without correction, women heavier or lighter than average weight had significantly different SPRs for Down's syndrome and NTD compared with those weighing close to the median weight. Both correction methods smoothed out the variability in the SPR for Down's syndrome to a similar degree, but reciprocal-linear regression was much better at reducing the variability in SPR for NTD and its use is therefore worthwhile.

Biomarkers↗
PubMed1997

Characterization of the canine type C enterotoxin produced by Staphylococcus intermedius pyoderma isolates.

The type C staphylococcal enterotoxins (SECs) are a group of highly conserved proteins with substantial antigenic cross-reactivity. Although Staphylococcus intermedius and coagulase-positive species of staphylococci are reported to produce SEC and other SEs, toxins produced by species other than Staphylococcus aureus have not been previously characterized. In this study we report the molecular, biological, and immunological properties of the canine SEC (SECcanine) expressed by pathogenic isolates of S. intermedius. The mature form of SECcanine has 239 amino acid residues and a pI of 7.0. Typical of the SEs, purified SECcanine induces an emetic response in monkeys and the proliferation of T cells in a Vbeta-dependent manner. Although SECcanine has >95% sequence identity to previously described SEC variants, its sequence is most related to SEC2 and SEC3. In contrast to the sequence similarity, the Vbeta profile induced by SECcanine is typical of that induced by SEC1. This result is likely explained by the conservation of a cysteine residue at position 26 in SECcanine; residues at this position have been previously shown to determine subtype-dependent differences in T-cell receptor interactions of other SEs. Overall, these results show that superantigen toxins produced by the multiple members of the genus Staphylococcus are highly conserved in respect to biological and structural properties. Further, the frequent association of SECcanine with pyoderma in dogs supports the notion that the toxins are important for staphylococcal survival and pathogenesis.

Alleles↗
PubMed1996

Comparison of the beta-toxins from Staphylococcus aureus and Staphylococcus intermedius.

The beta-toxins produced by Staphylococcus aureus and Staphylococcus intermedius were purified to homogeneity from culture supernatants. Although the toxin from S. aureus has been throughly studied, less is known about its unique counterpart from S. intermedius. This is the first reported purification and analysis of the S. intermedius beta-toxin. Both toxins have similar enzymatic properties, belong to the class of neutral sphingomyelinases C, and have a high specificity for sphingomyelin. They also hydrolyze lysophosphatidylcholine at a much slower rate, but have no activity toward phosphatidylcholine, phosphatidylethanolamine, or phosphatidylserine. The kinetic parameters determined for both proteins (apparent Km 1.4 mM, Vmax 100 mmol/min/microg protein) are identical. Despite these similarities, the size and amino acid composition of the two beta-toxins differ. Molecular mass values, determined by electrophoresis and gel filtration, indicate that the both enzymes are single polypeptides. The decrease in sphingomyelinase activity of S. aureus beta-toxin upon pretreatment with dithiothreitol (DTT) indicates the presence of a disulfide bond in the protein. In contrast, DTT has no effect on the enzymatic activity of S. intermedius beta-toxin. This observation is consistent with the absence of detectable cysteine residue in the protein. N-terminal amino acid sequences determined for the first 19 residues of both beta-toxins also differ, only nine of the first 19 residues are identical. Further evidence that the two proteins differ was obtained by immunological analysis which demonstrated crossreactivity but a lack of identity.

Amino Acid Sequence↗
PubMed1991

A double-blinded, randomized trial of hydrocortisone in acute hepatic failure. The Acute Hepatic Failure Study Group.

The Acute Hepatic Failure Study Group (AHFSG) has conducted a double-blinded, randomized evaluation of hydrocortisone in patients with acute hepatic failure. From July 1975 through August 1978, a 38-month period, 18 medical centers in the United States and one in Canada participated in this trial. A total of 64 patients were accessed and found eligible to participate in the study; two of them were subsequently eliminated from our analysis. Eighteen patients received placebo; 23 received 400 mg hydrocortisone per day, and 21 patients were administered 800 mg hydrocortisone per day. We did not observe any therapeutic effect of hydrocortisone, and the survival rates for placebo versus 400 mg and versus 800 mg hydrocortisone per day were 22%, 9%, and 24%, respectively. Fulminant hepatitis associated with drug hepatotoxicity or non-A, non-B hepatitis seemed to have a worse prognosis than fulminant B, although these differences were not significant. Serum alpha-fetoprotein had a modest prognostic value of survival and seemed to be limited to fulminant B. The AHFSG recommends, therefore, that corticosteroid use in acute hepatic failure with hepatic encephalopathy be discontinued.

Adult↗
PubMed1989

Prevalence of antibodies to human immunodeficiency virus type 1 among blood donors prior to screening. The Transfusion Safety Study/NHLBI Donor Repository.

The Transfusion Safety Study (TSS) and the National Heart, Lung, and Blood Institute (NHLBI) established a repository of approximately 200,000 sera from blood donors in late 1984 and early 1985. Collections were made in the four metropolitan areas with the highest prevalence of AIDS. Retrospective testing showed an overall anti-HIV-1 prevalence of 16 cases per 10,000 donations. In this study, the predictive value of a negative initial enzyme-linked immunoassay was estimated from both quality control specimens and the rescreening of 13,461 sera to be greater than 99.99 percent with respect to technical error. Among anti-HIV-1-positive persons, there was a 1.3- to 1.5-fold excess of first-time donors. The anti-HIV-1 prevalence among donors showed that infection was more common among young men than suggested by national reporting of AIDS cases. Anti-HIV-1 prevalence varied among the four metropolitan areas less than did reported AIDS cases, but, by 1987, the differences in the latter had decreased. Anti-HIV-1 prevalence in collection areas outside of the four major cities differed much more widely than that among the cities themselves. The TSS/NHLBI Donor Repository will remain available for the indefinite future for further evaluation of screening procedures for HIV-1 and other viruses for which transfusion is found to be an important route of transmission.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Reproducibility in quality control of protein (Western) immunoblot assay for antibodies to human immunodeficiency virus.

The protein (Western) immunoblot assay (IB) for antibodies to human immunodeficiency virus, like other laboratory procedures, sometimes gives variable results. In the Transfusion Safety Study, indistinguishable aliquots of four quality control (QC) samples have been routinely submitted for IB with each group of patient specimens. A false negative IB result was obtained for 1.7% of 179 assays of two known positive (QC) standards and a false positive result for 2.0% of 101 assays of two known negative (QC) standards. In addition, a test panel of 24 samples was sent on a single occasion to three widely used laboratories. A false positive result was reported by one laboratory and a false negative by a second. Although generally reliable, IB results may occasionally be in error. There is much more technical variability in the relative frequencies of antigen-antibody bands than has been recognized. These interlaboratory and intralaboratory comparisons show quality control checks are essential for all laboratories, and more than one specimen should be tested if its applicability to a specific patient is questionable. Specific bands are sufficiently inconstant for the same specimen to make appearance or disappearance on successive specimens prognostically unreliable.

Blotting, Western↗
PubMed1981

Serum alanine aminotransferase of donors in relation to the risk of non-A,non-B hepatitis in recipients: the transfusion-transmitted viruses study.

To evaluate the incidence of post-transfusion hepatitis and factors influencing its occurrence, the Transfusion-Transmitted Viruses Study prospectively followed 1513 transfusion recipients from 1974 through 1979. The attack rate for non-A,non-B hepatitis was 10 per cent. The incidence of hepatitis was directly related to the alanine aminotransferase (ALT) level in blood donors. In recipients of multiple transfusions of blood that had no donor-ALT level above 29 IU per liter the attack rate was 6 per cent or less; at higher donor-ALT levels the attack rate increased progressively, reaching 45 per cent in recipients of units with an ALT of 60 IU or greater. A similar relation was observed among recipients of single units of blood. Moreover, hepatitis developed in 10 of 11 recipients of two units with an ALT level of 45 IU or greater. These data indicate that screening blood for ALT levels would reduce the incidence of non-A,non-B post-transfusion hepatitis.

Adolescent↗
PubMed1981

A virologically studied epidemic of type A hepatitis in a school for the mentally retarded.

The occurrence of hepatitis A virus (HAV) infection in a small boarding school for mildly to moderately mentally retarded children in Umka, Yugoslavia, in the spring of 1979, six years after the last recognized occurrence, provided an opportunity to study the spread of the agent among 79 classroom and dormitory contacts. Only 51% of those who had entered subsequent to the prior outbreak had detectable antibody (anti-HAV) with immunoglobulin G predominance, and the proportion within the first six years of training did not vary. Both findings suggest a lack of endemicity during the interval. The outbreak ended spontaneously just before the summer vacation with an anti-HAV prevalence of 90%. The ratio of silent to overt cases was approximately 2:1. HAV was found in fecal samples from susceptible residents with inapparent infection as well as those with hepatitis. Among those with prior experience, there were no significant anti-HAV increases to suggest HAV reinfection in this group. Overall, 32% were seropositive for markers of past or chronic hepatitis B virus (HBV) infection, but this status did not correlate with sex, year of training, or HAV experience. Only one instance of HBV transmission was observed in the same interval as the 26 HAV infections.

Adolescent↗
PubMed1981

Studies on the maternal-infant transmission of the viruses which cause acute hepatitis.

Eighty-three women with acute icteric hepatitis during pregnancy were followed for evidence of viral transmission to their infants. Six women had acute hepatitis A as diagnosed by appearance of anti-HAV during convalescence. Except for passively acquired antibodies which were present at birth, anti-HAV did not appear in these infants, and there was no clinical or biochemical evidence for hepatitis during follow-up. Sixty-five pregnant women had acute hepatitis B during pregnancy or in the immediate postpartum period. Transmission to infants often occurred when both maternal HBsAg and HBeAg were positive at delivery of postpartum. A majority of these infants never developed jaundice, have remained persistently HBsAg-positive, and have had periodic serum ALT elevations during follow-up. Twelve women had acute non-A, non-B hepatitis during pregnancy. Infants born to 6 of these women near term had transient elevations of serum ALT values at 4-8 wk of age, suggesting maternal transmissibility of the non-A, non-B viral agent.

Acute Disease↗
PubMed1978

Viral hepatitis: lack of transmission in an Athenian School.

In the 1975-76 school year, 3 cases of icteric hepatitis occurred almost simultaneously in 2 grades of an Athenian school. An initial survey of the 2 classes approximately one week later found that 88 of 94 children were susceptible to type A hepatitis. No further clinical cases occurred. A second survey at the end of the school year revealed only 2 subclinical hepatitis A virus infections: one coincident with the overt cases in November, and a second from extramural exposure in February. Two carriers of hepatitis B virus in class A were not associated with serologic evidence for communicability of that agent in this setting. Testing of faecal specimens for agents possibly responsible for epidemiological interference with the spread of hepatitis A virus was unsuccessful. Nevertheless, the hypothesis of Band that other agents may interfere with transmission of hepatitis A virus deserves further study.

Child↗
PubMed1977

Prognostic implications of the e antigen of hepatitis B virus.

The e antigen HBeAg and its antibody anti-HB, have been said to be predictive of chronicity and resolution, respectively, in viral hepatitis. We found, as have others, a specific association with hepatitis B virus-induced disease. In addition, detectability of HBeAg in the acute phase of type B hepatitis was followed by a sixfold higher incidence of chronic hepatitis. Unfortunately, the prediction was erroneous in 65% of positive cases and 6% of negative cases. In chronic hepatitis, HBeAg did not necessarily disappear in advance of resolution, and its disappearance did not necessarily indicate resolution. Two patients with acute hepatitis progressing to chronicity were anti-HBe-positive in both phases, as were seven (5%) with chronic hepatitis. For individual patients, therefore, HBeAg and anti HBe are not prognostically useful indexes.

Acute Disease↗
PubMed1975

Hepatitis B virus infection in dentists.

To evaluate viral hepatitis as a hazard in general dentistry, we surveyed participants in an annual health-screening program at the 1972 American Dental Association session. Of 1245 practitioners, 0.9 per cent were positive for hepatitis B surface antigen, and 12.7 per cent were antibody positive. Of those who had had clinical hepatitis while studying or practicing dentistry, 43 per cent were seropositive. The frequency of evidence for prior infection with hepatitis B virus increased uniformly with increasing years of professional experience. The proportion of seropositive dentists did not vary with geographic region of the United States, or size of community. Only 10.5 per cent recognized illicit self-injection among patients, and their infection rate was not increased. These data indicate an increased frequency of infection with hepatitis B virus among general dentists, and are compatible with relatively uniform endemicity of subtype/ad strans of that agent in the general population for several decades.

Adult↗