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F E Preston

Publications and source records attributed to F E Preston.

At least 19 recordsLinked to original sources
PubMed1996

Investigation of the relative infectivity and pathogenicity of different hepatitis C virus genotypes in hemophiliacs.

To assess the relative infectivity and pathogenicity of variants of hepatitis C virus (HCV) genotypes, the distribution of genotypes in hemophilic patients who had been treated with nonvirally inactivated factor concentrates or cryoprecipitates prepared from local blood donors was compared with those found in the respective blood donor populations. Genotype frequencies differed markedly in the four countries investigated (Scotland, Hungary, South Africa, and Thailand) but in each, the HCV genotype distributions in hemophiliacs and blood donors were similar. In addition, HCV genotypes in recipients of commercially manufactured concentrates were similar to those found in the US general population. These findings provide no evidence that HCV genotypes differ significantly from each other in replication rate, transmissibility, or infectivity.

Hemophilia A↗
PubMed1996

Elevated von Willebrand factor antigen predicts deterioration in diabetic peripheral nerve function.

We have studied the temporal relationship of plasma von Willebrand Factor (vWF), a marker of endothelial damage, with the development of complications in 63 young diabetic patients (56 of whom were insulin-dependent) who took part in a prospective study. Results are presented from baseline to follow-up. In the group as a whole, no significant changes were found in any autonomic function tests, temperature discrimination threshold or nerve conduction velocities. Median motor and peroneal latency were significantly increased, while median motor, peroneal motor and sural sensory potentials were significantly decreased at follow-up compared with baseline (p < 0.001). There was a significant fall in mean plasma vWF antigen and ristocetin co-factor activity in the entire group. Within the group, we identified eight patients whose peroneal motor and sural sensory conduction velocities had decreased by over 2 ms-1. In these patients (Group A), baseline vWF antigen and activity were significantly higher than in the rest of the patients (Group B), (p = 0.04) and vWF antigen was still significantly higher after 3 years (p = 0.02). There were no differences between the groups in incidence of retinopathy, urinary albumin excretion rate or macrovascular disease. To assess the influence of glycaemic control on vWF, we first compared a matched group (C) of diabetic patients with similar HbA1 to that of group A, but with normal nerve conduction velocities: vWF was still significantly higher in group A compared with group C (p = 0.02). Furthermore, hierarchical regression showed that vWF predicted deteriorating nerve function independently of glycaemic control or the type of diabetes. Endothelial dysfunction may be associated with development of peripheral neuropathy in young diabetic patients.

Adult↗
PubMed1996

Wide variability in the sensitivity of APTT reagents for monitoring of heparin dosage.

AIM: To assess the sensitivity of activated partial thromboplastin time (APTT) reagents for monitoring heparin dosage using data from the UK National External Quality Assessment Scheme (NEQAS) for blood coagulation. METHODS: Data were reviewed from four surveys using samples prepared by addition of heparin to normal plasma in vitro and from two surveys in which samples were prepared using plasma from patients receiving heparin therapy (ex vivo samples). RESULTS: For both in vitro and ex vivo samples, notable differences between APTT reagents with respect to heparin sensitivity were noted. This indicates that a uniform therapeutic range of 1.5-2.5 calculated by the APTT ratio may not be appropriate for all reagents. Reagent sensitivity in ex vivo samples was substantially different to that in in vitro samples. CONCLUSIONS: The results of this large series of laboratories clearly indicate that reagent specific therapeutic ranges may be necessary, and that samples prepared by the addition of heparin to normal plasma in vitro can be misleading and should not be used.

Acute Disease↗
PubMed1996

The therapeutic range for heparin therapy: relationship between six activated partial thromboplastin time reagents and two heparin assays.

The activated partial thromboplastin time (APTT) is the most commonly used test for laboratory monitoring of unfractionated heparin therapy. Since there are differences between APTT reagents in respect of responsiveness to heparin the widely used therapeutic range of 1.5-2.5 (APTT ratios) may not be appropriate for all reagents. The aim of this study was to assess the relationship between 6 different APTT reagents using a manual technique, 2 of these reagents used in combination with a coagulometer, a heparin assay by protamine titration and a chromogenic anti-Xa assay. Samples from 42 patients treated with unfractionated heparin for thromboembolic disease were studied, 12 of whom were receiving warfarin therapy with International Normalised Ratios (INR) of > 1.3. For normal subjects, APTT results were highly dependent on the method used and statistically significant differences were noted. The ratio of patient to mean normal APTT was calculated for each APTT method. When 30 samples from heparinised patients (with INRs of < 1.3) were analysed manually, the APTT ranges equivalent to 0.2-0.4 u/ml heparin by protamine titration (by regression analysis) were 1.6-1.9 for Boehringer reagent (the least responsive) up to 2.2-2.9 for Instrumentation Laboratory reagent (the most responsive). The concentration of heparin associated on average with APTT ratios of 1.5-2.5 varied approximately twofold to threefold between reagents.

Adult↗
PubMed1996

Recommendations for the treatment of factor VIII inhibitors: from the UK Haemophilia Centre Directors' Organisation Inhibitor Working Party.

A strategy is described for the initial detection, management and elimination of factor VIII inhibitors arising in patients with congenital and acquired haemophilia A. It is suggested that children with severe haemophilia A should be screened every 3 months up to the age of 10 years for inhibitors using the Bethesda method. Factor VIII inhibitors arising in these patients should be abolished using immune-tolerance induction wherever possible. Such regimes should be started as early as possible, preferably when the inhibitor titre is < 10 Bethesda Units (BU)/ml, and should not be interrupted. High-intensity regimes are recommended for patients whose inhibitors exceed 10 BU. Autoantibodies to factor VIII giving rise to acquired haemophilia should be abolished using high-dose immunoglobulin or conventional immunosuppression. The choice of haemostatic agent for the treatment of severe bleeding should be based upon the clinical circumstances and the current inhibitor value, measured using both human and porcine factor VIII in the Bethesda assay. The past anamnestic response should also be considered when choosing treatment for minor bleeding episodes.

Blood Coagulation Factors↗
PubMed1995

Factor VIII gene inversions in severe hemophilia A: results of an international consortium study.

Twenty-two molecular diagnostic laboratories from 14 countries participated in a consortium study to estimate the impact of Factor VIII gene inversions in severe hemophilia A. A total of 2,093 patients with severe hemophilia A were studied; of those, 740 (35%) had a type 1 (distal) factor VIII inversion, and 140 (7%) showed a type 2 (proximal) inversion. In 25 cases, the molecular analysis showed additional abnormal or polymorphic patterns. Ninety-eight percent of 532 mothers of patients with inversions were carriers of the abnormal factor VIII gene; when only mothers of nonfamilial cases were studied, 9 de novo inversions in maternal germ cells were observed among 225 cases (approximately 1 de novo maternal origin of the inversion in 25 mothers of sporadic cases). When the maternal grandparental origin was examined, the inversions occurred de novo in male germ cells in 69 cases and female germ cells in 1 case. The presence of factor VIII inversions is not a major predisposing factor for the development of factor VIII inhibitors; however, slightly more patients with severe hemophilia A and factor VIII inversions develop inhibitors (130 of 642 [20%]) than patients with severe hemophilia A without inversions (131 of 821 [16%]).

Blotting, Southern↗
PubMed1995

Heterogeneity of hepatitis C virus genotypes in hemophilia: relationship with chronic liver disease.

In this study we have determined the hepatitis C virus (HCV) serotype and genotype in a cohort of 96 HCV-infected hemophiliacs and have examined the relationship between HCV genotype and severity of chronic liver disease as determined by liver biopsy. HCV serotype was determined by specific enzyme-linked immunosorbent assays (ELISAs) and genotype by restriction fragment length polymorphism (RFLP) and HCV viral sequencing. The pattern of genotype distribution was quite unlike that of HCV-infected United Kingdom (UK) blood donors in that five of the six known HCV genotypes were represented, 50% were type 1, 13% type 2, and 18% type 3. An unexpected observation was the presence of HCV genotype 4 in four patients and type 5 in two patients. An additional feature was the presence of mixed infection, detected in 14% and 7% by serotype and genotype analysis, respectively. Liver biopsies were available from 51 patients. Cirrhosis was present in five of 27 (19%) of individuals with type 1, in 2 of 9 (22%) with type 2, and 5 of 8 (63%) of those with type 3. The heterogeneous pattern of HCV genotype distribution in this cohort of patients and the observed relationship between the severity of the related liver disease and specific HCV genotype may have important implications with respect to the natural history and treatment of HCV-related chronic liver disease in infected hemophiliacs worldwide.

Alanine Transaminase↗
PubMed1995

Low risk of viral infection after administration of vapor-heated factor VII concentrate or factor IX complex in first-time recipients of blood components. International Factor Safety Study Group.

BACKGROUND: Vapor-heated human factor VII concentrate and human factor IX complex are both obtained from prothrombin complex, undergo similar methods of manufacture, and are subjected to an identical two-step vapor-heating process for virus inactivation. STUDY DESIGN AND METHODS: Intermediate-purity vapor-heated human factor VII concentrate and vapor-heated human factor IX complex were monitored for safety with regard to viral infection in the context of an International Factor Safety Study, a prospective study that follows the revised recommendations from the International Congress of Thrombosis and Hemostasis (ICTH). Because the rarity of the respective hereditary deficiencies would have made separate analyses unrealizable, the results were combined for the final analysis. Entry required that patients have no history of transfusion with any blood derivative. After the first infusion of the study drug, patients were monitored for 6 months for the development of non-A, non-B hepatitis (NANBH) and infection with hepatitis B virus (HBV) and for 15 months for infection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV). An event was defined as a positive result on any test for any infection. An alanine aminotransferase level more than 2.5 times the upper limit of normal on two consecutive occasions was defined as an event for NANBH. HBV infection was monitored with tests for three different HBV markers: the HBV surface antigen, antibody against the HBV surface antigen, and antibody against HBV core antigen. HCV and HIV infection were monitored with tests for HCV and HIV antibodies. RESULTS: The 25 patients who completed the study (1 has not completed the study and 1 dropped out) received a total of 434 infusions comprising 17 different production lots of the concentrates. Twenty patients were analyzable for NANBH and 25 for HCV and HIV infection. Since most patients had been given HBV vaccination, only 4 patients were analyzable for this end point. None of the patients showed evidence of having developed an event. These data satisfy ICTH criteria when the products are considered together, but vapor-heated factor VII concentrate does not qualify alone because there were only five patients in this group. CONCLUSION: Vapor-heated factor VII concentrate and vapor-heated factor IX complex are associated with a low risk of viral infection. Preliminary results are also presented, indicating that the concentrates are safe with regard to inhibitor development.

Adult↗
PubMed1995

The incidence of factor VIII inhibitors in the United Kingdom, 1990-93. Inhibitor Working Party. United Kingdom Haemophilia Centre Directors Organization.

Reports of all the factor VIII inhibitors arising in the United Kingdom in patients with haemophilia A during the years 1990-93 have been collated by the United Kingdom Haemophilia Centre Directors Organization. 32 new inhibitors were reported during this period, giving an average incidence of new inhibitors of 1.5 per 1000 patients registered per year. Although most occurred in patients with severe haemophilia under the age of 10, 29% occurred in patients whose VIIIC was > 3 iu/dl, and 38% in patients over the age of 10 years. The incidence of inhibitors rose during the study period, but this change was not statistically significant.

Adolescent↗
PubMed1995

Quality control and oral anticoagulation.

The introduction of the INR system for the monitoring of oral anticoagulant control represents a major advance, not only in terms of therapeutic efficacy but also in respect of patient safety. It is important to recognize that the system is only viable if careful attention is paid to the many important variables which contribute to its overall value. These include the choice of thromboplastin, assignation of ISI, determination of the mean normal prothrombin time and the method of end-point detection. Participation in independent external quality assessment schemes permits a unique opportunity for individual laboratories to identify, through laboratory performance analysis, problems relating to their own laboratory practice. Another major advantage, particularly of the larger schemes, is the identification of poor reagents and coagulometers and inconsistencies in their performance. One example of this is the recent identification of problems in respect of ISI assignment for thromboplastins used with coagulometers. This, in turn, provided the necessary stimulus to the potentially important development of calibrants for local ISI determination (21).

Administration, Oral↗
PubMed1995

DNA polymorphisms for carrier detection of hemophilia in Thailand.

The assessment of carrier state based on the pedigree and laboratory testing in 55 females from 34 Thai hemophilia families (24 affected by hemophilia A, 10 by hemophilia B) was studied. The laboratory testing included phenotypic analysis (FVIII:C/vWF: Ag ratio, FIX:C) and two types of DNA polymorphisms, restriction fragment length polymorphisms (RFLP) and variable number tandem repeats (VNTR) in/and close to the factor VIII genes (Bcl I, Xba I RFLP, St 14 VNTR) and factor IX genes (Mse I, Dde I RFLP). Fifteen out of seventeen (88%) obligate hemophilia A carriers and one out of five (20%) obligate hemophilia B carriers were diagnosed by phenotypic analysis. All hemophilia A carriers were informative for at least one polymorphism (Bcl I, Xba I or St 14) while 42% of hemophilia B carriers were informative for Mse I RFLP only. DNA polymorphism analysis has advantage over phenotypic analysis since it generally gives an absolute diagnosis when informative. Most DNA polymorphism analyses are performed by PCR technique which is a simple, inexpensive and quick procedure. However, it is limited by non-informativeness and high incidence of new mutations.

Factor IX↗
PubMed1994

Factor VIII gene rearrangements in patients with severe haemophilia A.

Sequences within intron 22 of the factor VIII (FVIII) gene have been implicated in the cause of haemophilia in almost 50% of severely affected patients. The changes result from intrachromosomal rearrangements of the tip of the long arm of the X chromosome, one break-point being within intron 22 of the FVIII gene. The rearrangements can be identified by Southern blot and we report use of this procedure to detect rearrangements in 11 of 23 unrelated families with severe haemophilia A. Of 22 patients studied, none of the 10 with the gene rearrangement had at any time developed inhibitors to FVIII, compared with 7 of 12 lacking the rearrangement.

Adult↗