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Biomedical subjects

H G Watson

Publications and source records attributed to H G Watson.

36 records · Page 2Linked to original sources

Combined risk factors contributing to cerebral venous thrombosis in a young woman.

Cerebral venous thrombosis is a rare condition affecting predominantly adolescents or young adults. The presentation is often non-specific, and delay in diagnosis is common. The otolaryngologist may be consulted about the radiological findings of lateral sinus thrombosis and mastoid changes. The association of congenital thrombophilia with unusual presentations of venous thrombosis, especially in young individuals is now well documented. We present a case of lateral and sagittal sinus thrombosis complicated by cerebral venous infarction in a girl with protein C deficiency and masked mastoiditis. Unusual forms of venous thrombosis, including cerebral venous thrombosis may develop in association with a single risk factor for thrombosis, but additional risk factors should be sought especially when thrombosis presents in very young individuals. This case draws attention to the multi-causal nature of cerebral venous thrombosis in young adults, and highlights the issue of masked mastoiditis. A coordinated approach by otolaryngological and haematological teams is recommended in such cases.

Adolescent↗

Sight-threatening varicella zoster virus infection after fludarabine treatment.

Varicella zoster virus (VZV) infection involving the posterior segment of the eye after fludarabine treatment has not previously been described. Two patients, who had completed fludarabine treatment 3 and 18 months previously, presented with visual loss that had been preceded by a recent history of cutaneous zoster. The use of the polymerase chain reaction (PCR) for VZV DNA from ocular specimens allowed rapid confirmation of clinical diagnosis and treatment with a good outcome in one patient. With the increasing use of fludarabine and other purine analogues, an awareness of such complications is important because of their potentially sight-threatening consequences.

Acyclovir↗

Transfusion associated graft versus host disease in an immunocompetent individual following coronary artery bypass grafting.

Transfusion associated graft versus host disease (TA-GVHD) is a rare but commonly fatal complication of transfusion of cellular blood products, which usually occurs in immunosuppressed individuals following transfusion and subsequent engraftment of viable T lymphocytes. Very rarely it may arise in apparently immuno-competent individuals. A case is reported of TA-GVHD in a non-immunocompromised 60 year old white man, resulting from red cell transfusion after coronary artery bypass grafting. HLA typing confirmed homozygosity of the donor for an HLA type shared by the recipient--the classic scenario for the development of TA-GVHD in immunocompetent individuals. The patient died 21 days after transfusion. There is a perceived increased risk of TA-GVHD following bypass grafting and other surgical procedures where cardiopulmonary bypass is required. TA-GVHD is probably underreported and the incidence in the UK is felt to be too low to warrant routine irradiation of cellular products for this group of patients. Clinicians, pathologists, and transfusion centres should be aware of this rare but devastating complication of blood transfusion after cardiac surgery.

Coronary Artery Bypass↗

Evolution of zidovudine resistance-associated genotypes in human immunodeficiency virus type 1-infected patients.

Substantial differences have been described in the response of individual patients to zidovudine (ZDV) therapy, both in the clinical impact and in virus load. Genotypic changes associated with the appearance of drug resistance may also be different or occur at different rates. We have obtained the nucleotide sequence of the RT domain of individual HIV-1 genomes extracted from 10 plasma and peripheral blood mononuclear cell (PBMC) samples donated by two haemophiliac patients before, during, and after long-term ZDV therapy. Although the plasma virus load was similar throughout, the order and timing of appearance of resistance-associated substitutions differed in the two patients. In patient p74, K70R appeared after 4 months, T215Y at 5.5 months, and M41L at 13 months. In p87, K70R also appeared at 4 months, but T215Y and K219Q were not observed until 18 months and M41L not at all. Much greater sequence change overall occurred in p74. The evolution of the viral population in that patient was dominated by the unique appearance of T215Y and subsequently M41L, with all sequences from the last time point being descended by a single path from the pretreatment samples. However, in p87, several different lineages of RT sequences were found to persist throughout treatment. We propose that these differences in outcome may be determined by differences in genetic background at sites other than the five generally considered to be associated with ZDV sensitivity.

Amino Acid Sequence↗

Absence of hepatitis A virus transmission by high-purity solvent detergent treated coagulation factor concentrates in Scottish haemophiliacs.

Recent reports of hepatitis A virus (HAV) infection in haemophiliacs receiving high-purity solvent detergent (HP.SD) treated factor VIII concentrates have brought into question the efficacy of this virucidal method for inactivating HAV. To assess whether HAV may have been transmitted by HP.SD concentrates, we compared seroprevalence in haemophiliacs with different disease severity, sought evidence of seroconversion to HAV since introduction of HP.SD products, and directly examined concentrates for HAV RNA by PCR. Our data suggest that Scottish haemophiliacs are not being infected with HAV by HP.SD concentrates produced initially by CRTS Lille and presently by PFC Edinburgh and supplied by the Scottish National Blood Transfusion Service (SNBTS).

Adolescent↗

Frequent reinfection and reactivation of hepatitis C virus genotypes in multitransfused hemophiliacs.

The frequency and dynamics of infection with different genotypes of hepatitis C virus were investigated in a cohort of hemophiliacs repeatedly exposed to non-virus-inactivated clotting factor. Among 63 infected hemophiliacs, genotype 1 (n = 38, subtypes 1a [27] and 1b [11]) was predominant; genotypes 2a (n = 1), 2b (n = 3), 3a (n = 20), and 5a (n = 1) accounted for the remainder. This distribution was similar to that found in Scottish blood donors from whom the infected blood products were manufactured. Hemophiliacs with severe disease were more likely to be polymerase chain reaction-positive than those with moderate or mild disease. Over 10 years, changes in the circulating major genotype and serotype were observed in 9 of 29 hemophiliacs and from one subtype to another in 3, although there was no clear trend toward replacement with any particular variant. Replacement occurred after the introduction of inactivated clotting factor in 4 subjects, implicating reactivation rather than reinfection. Those coinfected with human immunodeficiency virus were more likely to show a change in genotype.

Blood Donors↗

Virus-associated haemophagocytic syndrome: further evidence for a T-cell mediated disorder.

A 16-year-old youth with life-threatening virus-associated haemophagocytic syndrome (VAHS) responded remarkably to treatment with cyclosporin A during two periods of active disease, the second of which was due to noncompliance with treatment. Our clinical observations support the hypothesis that VAHS is cytokine driven as a result of an aberrant T-cell response to infection.

Adolescent↗

Warfarin and epistaxis--a case controlled study.

Patients anticoagulated with warfarin form a small proportion of those admitted with epistaxis annually to ENT units. The authors formed the impression that such patients spend longer in hospital and have more complicated management than controls. A prospective age and sex matched controlled study of 20 consecutive patients admitted with epistaxis whilst anticoagulated was performed. This showed that these patients spent significantly longer in hospital than controls, with an additional expense in the study period of 10,500 pounds for inpatient bed nights alone. The management of these patients is more complicated and there is a subgroup of poorly controlled patients who present most of the problems. A potential solution is to improve community warfarin control and to involve general practitioners and haematologists in the re-establishment of warfarin following admission for epistaxis.

Aged↗

Immunological abnormalities in haemophiliacs.

10 years ago, it became apparent that haemophiliacs were developing diseases which were indicative of underlying immunodeficiency. The results of investigation confirmed that many had abnormal immune systems, particularly with regard to cell-mediated immunity. These abnormalities were thought to be a consequence of the use of clotting factor concentrates, and indeed the discovery of HIV and its mode of transmission, confirmed these suspicions. However, it subsequently became clear that HIV infection did not explain all the abnormalities observed. Many in vivo studies have shown that the immune systems of HIV-negative haemophiliacs are not entirely normal, and in vitro studies have shown that clotting factor concentrates per se have a modulating effect on immune function. We have reviewed particularly the abnormalities seen in HIV-negative haemophiliacs and their possible causes, as well as the specific features of HIV infection in haemophiliacs.

Blood Coagulation Factors↗

Use of several second generation serological assays to determine the true prevalence of hepatitis C virus infection in haemophiliacs treated with non-virus inactivated factor VIII and IX concentrates.

To investigate the prevalence of hepatitis C virus infection in two risk groups, stored serum samples from treated haemophiliacs and intravenous drug users were tested for anti-HCV by both anti-C-100 based and second generation ELISAs (Abbott and Ortho) followed by testing in two confirmatory immunoblot assays that incorporate core as well as other non-structural antigens (Innogenetics LIA and Chiron RIBA-HCV test). Clear evidence of HCV infection was found in all but one of 78 haemophiliacs treated with non-virus inactivated clotting factor concentrates, but in none exposed only to super dry heat-treated concentrates. Only four samples gave rise to conflicting serological results between the four tests, two of these occurred in patients with advanced HIV related disease and almost certainly reflected loss of humoral immunity associated with disease progression, and the others occurred in the only two patients tested who were chronic carriers of hepatitis B infection and may reflect an interaction between the two viruses. Comparison of anti-C-100 versus second generation tests in immunocompetent drug users revealed a false negative rate of 20% using C-100 alone, indicating the advantage of using second generation assays for detection of past or current HCV infection. Of all of the antigens used in the confirmatory assay, positive sera showed strongest and most frequent reactivity with the C22 and C33c proteins (Ortho RIBA).

Drug Contamination↗

An HIV positive haemophiliac with acute lymphoblastic leukaemia successfully treated with intensive chemotherapy and syngeneic bone marrow transplantation.

A 26-year-old HIV positive severe haemophiliac developed Burkitt-type acute lymphoblastic leukaemia with intracranial involvement. He underwent standard combination therapy, and entered complete remission. Syngeneic bone marrow transplantation (BMT) was undertaken; the donor was also HIV positive. The patient died 18 months from transplant of isolated intracranial relapse, with no evidence of systemic relapse. Unlike other types of non-Hodgkin's lymphoma, Burkitt's type occurs in HIV positive patients with relatively normal CD4 cell counts. Remission can be achieved using intensive chemotherapy, and since these patients may otherwise have a reasonable life expectancy, BMT may be appropriate.

Adult↗

Hepatitis C quantification and sequencing in blood products, haemophiliacs, and drug users.

The polymerase chain reaction (PCR) detected specific hepatitis C viral (HCV) RNA sequences in plasma from 15 of 21 haemophiliacs (12 HCV-antibody positive) and 7 of 27 intravenous drug users (13 HCV-antibody positive). Quantification of RNA-positive samples showed high levels of HCV (10(5) to 10(6) copies of RNA/ml) in infected patients. HCV was more frequently found in haemophiliacs infected with human immunodeficiency virus (11/11 HIV-positive and 4/10 HIV-negative patients). HCV-RNA was detected in all batches of commercially available factor VIII tested and in low concentrations in some pools of plasma donations from volunteers. Factor VIII, manufactured from volunteer donations, was uniformly negative by PCR. Phylogenetic analysis of viral sequences showed two distinct groups: one was associated with intravenous drug users and the other with haemophiliacs infected with Scottish factor VIII preparations. Both were distinct from sequences found in commercially available factor VIII.

Acquired Immunodeficiency Syndrome↗