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Biomedical subjects

K N Ward

Publications and source records attributed to K N Ward.

At least 37 records · Page 2Linked to original sources
PubMed1996

Cytomegalovirus antibody avidity in allogeneic bone marrow recipients: evidence for primary or secondary humoral responses depending on donor immune status.

The reconstitution of the human cytomegalovirus (CMV) antibody response in CMV seropositive bone marrow transplant patients was investigated by comparing 11 patients whose donors were CMV seropositive with 8 whose donors were CMV seronegative. Evidence for primary or secondary responses to CMV was sought by determining IgG antibody avidity using an avidity index method, and antibody titre over a period of up to 3 years after transplant. For the patients whose donors were CMV seropositive, the results showed the characteristics of a secondary response, i.e., rising antibody titres of high avidity immediately after transplant. In contrast, the patients with CMV seronegative donors showed evidence of a primary antibody response usually occurring at about 250 days after transplant, i.e., rising antibody levels initially of low avidity maturing to high avidity over the following 100 to 200 days. It is concluded that a secondary response and hence transfer of humoral immunity had occurred in those patients whose donor was CMV seropositive, whereas a delayed primary response occurred in those patients whose donor was CMV seronegative.

Antibodies, Viral↗
PubMed1995

Bone marrow transplantation for chronic myeloid leukemia with volunteer unrelated donors using ex vivo or in vivo T-cell depletion: major prognostic impact of HLA class I identity between donor and recipient.

Between August 1985 and July 1994, we performed 115 volunteer unrelated donor (VUD) bone marrow transplants (BMT) for first chronic phase (n = 86) or advanced phase (n = 29) chronic myeloid leukemia (CML). Standard serologic HLA typing of potential donors and recipients was supplemented with one-dimensional isoelectric focusing (IEF) for class I proteins, allogenotyping for DR and DQ alleles using DNA restriction fragment length polymorphism (RFLP) analysis, and the measurement of antirecipient major histocompatibility complex (MHC) cytotoxic T-lymphocyte precursor cells in the donors' blood (CTLp assay). Recipients were conditioned for transplantation with a combination of high-dose chemotherapy and total body irradiation (n = 103) or high-dose chemotherapy alone (n = 12). Twenty eight recipients received ex vivo T-cell-depleted marrow, and 84 underwent some form of in vivo T-cell depletion. The probability of severe (grades III or IV) acute graft-versus-host disease (aGVHD) was 24%, and that of extensive chronic graft-versus-host disease (cGVHD), 38%. Proportional hazards regression analysis showed an association between low frequency CTLp and a reduced incidence of severe aGVHD (relative risk [RR], 0.28; P = .0035). The probability of relapse at 3 years was 23%, with first chronic phase disease being independently associated with a lower risk of relapse (RR, 0.71; P = .01). The overall leukemia-free survival (LFS) at 3 years was 37%; the LFS for the first chronic phase and advanced phase recipients was 41% and 26%, respectively. First chronic phase disease (RR, 0.56; P = .063) and the combination of recipient cytomegalovirus (CMV) seronegativity and an IEF-matched donor (RR, 0.48; P = .011) were both associated with improved LFS. The probabilities of survival and LFS for patients under 40 years of age transplanted in first chronic phase from an IEF-matched donor were 73% and 50%, respectively. We conclude that VUD BMT is a reasonable option for patients with CML; when using ex vivo or in vivo T-cell depletion, optimal results are achieved in patients transplanted in chronic phase with marrow from donors without demonstrable class I HLA mismatch and a low CTLp frequency.

Adolescent↗
PubMed1995

The spectrum of hepatitis C antibody positive disease in a teaching hospital.

OBJECTIVE: To survey clinical associations of a positive hepatitis C virus antibody (HCV-antibody) test. DESIGN: Retrospective analysis of all positive HCV-antibody tests reported by a Virology Department. SETTING: A complex secondary and tertiary care teaching hospital. PATIENTS: 144 confirmed cases with HCV-antibody in serum, identified from approximately 2,500 clinical specimens tested. RESULTS: Over 99% of positive tests were in the following groups: liver dysfunction; multiply transfused individuals; intravenous drug abusers; patients with bleeding disorders; and renal replacement therapy. Amongst the patients with liver disease--the only group in which a known epidemiological association was not the indication for testing--over 25% of patients had no risk factor identifiable, representing 7.5% of the total group of HCV-antibody positive patients. CONCLUSION: Selective HCV-antibody testing in a U.K. hospital population reveals a substantial population of positive patients, and risk factors for hepatitis C are not always present.

Adolescent↗
PubMed1995

Treatment of adenoviral pneumonitis with intravenous ribavirin and immunoglobulin.

A 67 year old woman developed a severe adenoviral pneumonitis whilst receiving immunosuppressive therapy. She showed clinical and radiological evidence of a response to treatment with nebulised and intravenous ribavirin and intravenous pooled normal human immunoglobulin. To our knowledge this is the first time that such a therapeutic approach has been used in the treatment of a condition which normally carries a very high mortality.

Adenoviridae Infections↗
PubMed1994

Primary human herpesvirus-6 infection is frequently overlooked as a cause of febrile fits in young children.

Sera from 248 children aged 30-179 weeks were tested retrospectively for human herpesvirus-6 (HHV-6) IgG antibody avidity. Twenty-five children presented with febrile fits, in one case with a rash, exanthem subitum resulting from primary HHV-6 infection was diagnosed at the time, but in the others HHV-6 was not considered in the differential diagnosis even though two patients had a rash. In fact, five of the 25 patients experienced primary infection as shown by low avidity HHV-6 antibody. Although nine other of these patients were seronegative in the acute phase of the illness, and unfortunately convalescent sera were not available to confirm primary HHV-6 infection, seronegativity was clearly a risk factor for febrile fits (P = 0.03, odds ratio 3.14 for all children; P = 0.002, odds ratio 7.20 for children aged 70-179 weeks), and primary HHV-6 infection was a very likely diagnosis. The remaining 11 children had high avidity antibody, so HHV-6 was excluded as a cause of their febrile fits. HHV-6 may frequently be a cause of febrile fits, often without the typical rash of exanthem subitum, and this diagnosis is often overlooked by clinicians.

Antibodies, Viral↗
PubMed1994

Measurement of antibody avidity for hepatitis C virus distinguishes primary antibody responses from passively acquired antibody.

A new IgG antibody avidity test for hepatitis C virus (HCV) has been developed and was validated using sera from 12 renal dialysis patients infected with HCV. In primary HCV infection low avidity antibody (mean avidity index 24%) was detected within 50 days of seroconversion whereas in long-term infection (at least 300 days after seroconversion), the mean avidity index was high (88%); in five patients, the avidity index was shown to increase rapidly as time elapsed after primary infection, whereas immunosuppressive therapy was found to delay maturation of the immune response in two further patients. The assay was then employed to confirm that a spurious outbreak of primary HCV infection in eight bone marrow transplant patients was explicable by passive acquisition of high avidity anti-HCV after intravenous immunoglobulin therapy. It is concluded that this avidity test will have an important role in the investigation of HCV infection in patients.

Antibody Affinity↗
PubMed1994

Maturation of antibody avidity after primary human cytomegalovirus infection is delayed in immunosuppressed solid organ transplant patients.

An IgG antibody avidity assay which uses urea to modify a commercial enzyme-linked immunosorbent assay (ELISA) has been investigated for its ability to distinguish primary human cytomegalovirus (CMV) from recurrent or long-term infection. Twenty-four immunosuppressed solid organ transplant patients were studied. The avidity indices for IgG to CMV were low for 12 out of 13 patients with primary infection (mean 18%), high for all 11 patients with long-term infection (mean 85%), and the 1 patient with primary infection showing an intermediate avidity index (51%) was found to have acquired passively large amounts of CMV immunoglobulin, presumably of high avidity, during therapy. From the results, low and high avidity indices were defined as lying between 0-34% and 60-100%, respectively, and it was thus clear that the avidity assay can discriminate between primary and recurrent or long-term CMV infection. The avidity indices of eight of the immunosuppressed organ transplant patients with primary infection were followed in serial serum samples over time and IgG antibody to CMV was found to take at least a year to mature to high avidity in contrast to the 2-6 months expected for normal subjects. This finding provides evidence that immunosuppression has subtle, hitherto unsuspected, effects on humoral immunity to CMV in addition to the well-known depression of cell-mediated responses. It is concluded that this reliable avidity assay will be of importance in the diagnosis of CMV infection and in elucidating the pathogenesis of CMV-induced disease in organ transplant recipients.

Adult↗
PubMed1993

Allogeneic bone marrow transplantation for chronic myeloid leukemia using sibling and volunteer unrelated donors. A comparison of complications in the first 2 years.

OBJECTIVE: To compare the short- and medium-term complications (particularly infection) of bone marrow transplantation for chronic myeloid leukemia in patients with HLA-identical sibling donors or volunteer unrelated donors. DESIGN: Retrospective review of two cohorts of patients. SETTING: Tertiary referral center. PATIENTS: One hundred three patients with chronic myeloid leukemia in first chronic phase. INTERVENTION: Patients were treated with bone marrow transplantation using marrow from HLA-identical siblings (n = 57) and volunteer donors (n = 46). MAIN RESULTS: In total, 68 patients survived a median of 22 months from bone marrow transplant (range, 7 to 81 months). The actuarial probabilities of overall survival and leukemia-free survival at 2 years for the sibling donor group were 73% (95% CI, 60% to 86%) and 72% (CI, 60% to 84%), respectively, and for the volunteer donor group, 47% (CI, 31% to 63%) and 42% (CI, 26% to 58%) (P = 0.07 and 0.05, respectively). However, after adjustment for duration of disease, overall and disease-free survival in the two donor groups did not differ significantly. A major problem was an increased incidence of severe viral infection in the volunteer unrelated donor group (19 episodes in 16 of 46 patients compared with 7 episodes in 7 of 57 sibling donor patients, P = 0.01). The actuarial incidence of chronic graft-versus-host disease (GVHD) was higher in volunteer unrelated donor patients (77% [CI, 63% to 91%] compared with 49% [CI, 35% to 63%]; P = 0.02) but that of acute GVHD was not. The median performance status of the survivors in the volunteer donor group is similar to that in the sibling donor group. The incidence of hematologic relapse in both groups so far is low. CONCLUSION: Results appear to justify the continued use of volunteer donors in chronic-phase chronic myeloid leukemia, but infection and chronic GVHD are still major problems.

Actuarial Analysis↗
PubMed1993

Chronic liver disease due to hepatitis C.

The low concentration of hepatitis C virus in the blood of infected patients has made it difficult to detect. Infected patients can now be identified by using more sensitive immunoassays and amplification of viral RNA by the polymerase chain reaction. Nevertheless, the virus remains difficult to eliminate. We present the case of a woman with a history of autoimmune haemolytic anaemia, thrombocytopenia, and common variable immunodeficiency who developed chronic hepatitis.

Adult↗
PubMed1993

Avidity of IgG antibodies to human herpesvirus-6 distinguishes primary from recurrent infection in organ transplant recipients and excludes cross-reactivity with other herpesviruses.

A newly developed IgG antibody avidity test for human herpesvirus-6 (HHV-6) was used in a study of primary and recurrent HHV-6 antibody responses in immunocompromised solid organ graft recipients. In a primary HHV-6 infection low avidity antibody was detected which matured to high avidity within 5 months whereas, in contrast, high avidity antibody was found in three recurrent infections thus showing the ability of the test to discriminate between primary and recurrent infection in immunosuppressed patients. Six HHV-6 seropositive transplant patients who experienced a subsequent primary human cytomegalovirus (CMV) infection had high avidity concurrent HHV-6 antibody rises, thus excluding a cross-reaction from the low avidity antibodies generated in the primary CMV response and providing evidence of recurrent HHV-6 infection. Four further HHV-6 seropositive patients with proven primary Epstein-Barr virus (EBV) infection were also studied; in each of these cases high avidity HHV-6 antibody rises were seen likewise suggesting recurrent HHV-6 infection. The test is therefore of value in the investigation of herpesvirus infections in transplant patients.

Adolescent↗
PubMed1993

IgG antibodies to human herpesvirus-6 in young children: changes in avidity of antibody correlate with time after infection.

Sera from 321 children aged 0-179 weeks and 196 adult blood donors were examined for IgG antibodies to human herpesvirus-6 (HHV-6) using an indirect immunofluorescence test. After birth, antibody prevalence declined to a minimum between 20 and 29 weeks. Thereafter the percentage of individuals with antibody increased up to the age of 60-69 weeks after which the prevalence of antibody in the children remained stable at about 88%; in contrast, the seroprevalence in blood donors was 98%, indicating that some individuals remain susceptible to infection after early childhood but that virtually all are infected by the time they reach adulthood. The HHV-6 antibody titre increased steadily over the first 70 weeks of life and then remained stable up to 179 weeks old at a level significantly higher than that of the adults. Two hundred and eighteen of the 321 sera whose HHV-6 antibody titres were 40 or greater were tested for antibody avidity using a modification of the immunofluorescence test whereby low avidity antibody was eluted with urea. The results show that the age distribution of low avidity antibody closely parallels the known distribution of exanthem subitum and, moreover, that the mean antibody avidity increased with time after primary infection. The method was further validated because well-characterised convalescent sera taken from seven children within 3 weeks of exanthem subitum all contained low avidity antibodies. The data presented in this study indicate that low avidity IgG to HHV-6 may be detected after primary infection and that this should prove useful in diagnosis and for seroepidemiological surveys.

Adult↗
PubMed1991

Primary and recurrent cytomegalovirus infections have different effects on human herpesvirus-6 antibodies in immunosuppressed organ graft recipients: absence of virus cross-reactivity and evidence for virus interaction.

The relationship between serum antibodies to human herpesvirus-6 (HHV-6) and cytomegalovirus (CMV) infection was studied in immunosuppressed adult organ graft recipients all of whom had IgG to both HHV-6 and Epstein-Barr virus capsid antigen (EBVCA) before operation and who had received an organ or organs from HHV-6 seropositive donors. In primary CMV infection the titre of IgG to HHV-6 rose substantially (between 32- and 512-fold) in eight out of eight patients whereas IgG to EBVCA only rose 32-fold in two patients. Moreover, the HHV-6 responses coincided closely with the CMV seroconversion. Serum absorption studies gave no evidence for antibody cross-reaction between CMV and HHV-6 because the CMV antibody titre could be reduced specifically without affecting HHV-6 antibody titres and vice versa. In recurrent CMV infection, HHV-6 antibody levels rose (32-fold) in three out of eight patients but these changes did not coincide with the CMV antibody response. Similarly, in the complete absence of CMV infection, five out of eight patients showed antibody rises to HHV-6 (between four- and 16-fold). IgG titres to EBVCA were stable in both these groups of patients. It is concluded that there is serological evidence (rising titre greater than or equal to four-fold) for genuine HHV-6 reactivation or, alternatively, for reinfection in 16 out of the 24 patients. This phenomenon was most frequent in primary CMV infection where the largest HHV-6 antibody responses were seen probably because of an, as yet, undetermined interaction between the two viruses.

Acute Disease↗
PubMed1991

Hepatitis A outbreak involving bread.

An outbreak of hepatitis A involved more than 50 residents of a group of villages in the late spring and summer of 1989. The only food that was common to all the laboratory-confirmed cases was bread, purchased either unwrapped or as rolls, sandwiches or filled rolls, and supplied either directly from one shop or indirectly through its subsidiary outlets. It was concluded that this bread was the most likely vehicle of transmission of the hepatitis A virus and that the bread was contaminated by soiled hands which were inadequately washed because of painful skin lesions. Comprehensive control measures were successful in limiting further spread of the infection. This outbreak highlights the transmissibility of hepatitis A virus on food. The use of disposable gloves when handling food which is to be consumed without further cooking would prevent transmission of this or other infectious agents by this route.

Bread↗
PubMed1989

Brief report: primary human herpesvirus 6 infection in a patient following liver transplantation from a seropositive donor.

A virus, isolated from peripheral blood lymphocytes of a patient 23 days after liver transplantation, was identified by negative contrast and thin-section electron microscopy, DNA hybridisation, and immunofluorescence as human herpesvirus 6 (HHV-6). The patient was seronegative for antibodies to HHV-6 before receiving the liver from a seropositive donor. Seroconversion for IgM and IgG antibodies occurred at the same time as the viraemia, indicating a primary response to HHV-6 infection that was probably acquired from the donor liver. The relationship of the infection to the patient's subsequent disease episodes is discussed.

Adult↗