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Biomedical subjects

P D Griffiths

Publications and source records attributed to P D Griffiths.

At least 235 records · Page 13Linked to original sources
PubMed1989

Cytomegalovirus infection and progression towards AIDS in haemophiliacs with human immunodeficiency virus infection.

To examine whether cytomegalovirus (CMV) infection could accelerate progression of human immunodeficiency virus (HIV) infection to AIDS, serological studies were done on 108 HIV-infected haemophiliacs. In the 1.3-9 years from time of first recognised HIV seroconversion, the age-adjusted risk of CDC group IV disease in CMV-seropositive patients was 2.5 times that in CMV-seronegative patients. CMV-seropositive patients were also more likely to have detectable p24 antigenaemia. Survival analysis showed that CMV-seropositive patients were at greater risk of HIV disease than CMV-seronegative patients from about 2 years after HIV seroconversion. Thus CMV infection is associated with a more rapid progression to HIV disease.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Titration of IgG antibodies against varicella zoster virus before bone marrow transplantation is not predictive of future zoster.

Serum antibodies to varicella zoster virus (VZV) were measured in 77 patients about to undergo allogeneic bone marrow transplantation, and in 65 of their donors. Ten patients developed zoster within the first 6 months following transplant. There was no significant difference in the mean pretransplant antibody titre between those patients who did or did not subsequently develop zoster. Likewise, the level of antibody to VZV amongst donors had no effect on the subsequent development of zoster. We conclude that the pretransplant level of antibody to VZV is not predictive of subsequent zoster infection, and would not be helpful in identifying patients for trials of antiviral prophylaxis. These results contrast with those previously found for another herpesvirus, herpes simplex (HSV), where antibody level pretransplant is predictive of future HSV recurrence.

Adolescent↗
PubMed1989

Diagnosis, treatment and outcome of pneumonia in the acquired immune deficiency syndrome.

Fibreoptic bronchoscopy was performed in 43 of 52 consecutive patients with opportunistic pneumonia in the acquired immune deficiency syndrome (AIDS). The 15 patients in whom a likely pathogen was not found by bronchoscopy (including the nine not having the procedure) were treated for Pneumocystis carinii pneumonia (PCP) alone and all responded. In 11 of these a diagnosis of AIDS was confirmed because of an alternative opportunistic infection within 6 months. PCP was confirmed in 38 of the 52 patients and cytomegalovirus (CMV) was isolated from 15 patients. The lower the partial pressure of arterial oxygen (PaO2) on admission the more likely was a pathogen to be found by bronchoscopy. The admission PaO2 while the patient was breathing room air was the single most reliable prognostic indicator. The mean PaO2 for survivors was 9.6 kPa and 6.7 kPa for non-survivors (P less than 0.01 Student's t-test), with 50% mortality for patients with a PaO2 of less than 8 kPa on admission. Temperature and pulse rate were sensitive indicators of response to treatment, obviating the need for frequent arterial gas measurements and chest radiography. Our findings suggest that although fibreoptic bronchoscopy contributed little to the treatment and final outcome of the infection, it identified the causative pathogen in most patients.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Diagnosis of cytomegalovirus infection.

CMV is an important pathogen for immunocompromised patients. Since such individuals cannot be relied upon to mount appropriate immune responses promptly, methods for detecting virus must be used for diagnosis. Conventional virus isolation is slow and the sensitivity and specificity of a more rapid method using monoclonal antibodies are described. Other potential ways of detecting cytomegalovirus are discussed, including the difficulties of detecting this virus immunochemically in clinical specimens due to its coating of human beta 2-microglobulin.

Antibodies, Monoclonal↗
PubMed1989

The natural history of human immunodeficiency virus infection in a haemophilic cohort.

112 haemophilic patients infected with HIV were followed up with clinical and laboratory assessment between 1 December 1979 and 30 November 1988. Sixty-six (59%) of the patients developed HIV-related clinical symptoms and 22 (20%) developed AIDS. Twenty (18%) of the patients developed p24 antigenaemia. Amongst the 59 patients whose date of seroconversion could be estimated the calculated 8-year cumulative incidence of AIDS was 40% (symptoms 73%). For the whole cohort of 112 patients, the median slope of linear regression of the absolute T4 lymphocyte count was steeper for those with AIDS (-0.113 x 10(9)/l per year) than for those without AIDS (-0.054 x 10(9)/l per year) (P less than 0.02). While 15 cases of AIDS developed during 58 patient-years of follow up after falling below a T4 lymphocyte count of 0.2 x 10(9)/l, only two cases occurred during 450 patient-years before reaching this count. Thus the decline of the T4 lymphocyte count to 0.2 x 10(9)/l may be an appropriate additional end-point for the assessment of new treatments for asymptomatic patients infected with HIV.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Effect of pregnancy plasma upon in vitro parameters of cell mediated immunity.

Pregnant women were classified according to their serological status for cytomegalovirus, herpes simplex virus or rubella virus. Lymphocytes taken from non-pregnant women were shown to be able to recognise viral antigens and the mitogen phytohaemagglutinin by the measurement of proliferative responses and by the production of gamma interferon. Proliferative responses or gamma interferon production were greatly reduced in the presence of plasma taken during the first, second or third trimester and immediately post-partum. The responses then gradually returned to normal after delivery. The availability of serial sera taken before pregnancy as well as during and after pregnancy in individual women showed that this effect was maintained even when sera had been stored frozen for more than one year. Mixing experiments were performed to vary the proportion of pregnancy serum in any particular assay but this did not prove that pregnancy sera were actively suppressive. Instead, the data suggest that pregnancy sera are deficient in some factor or factors which are required to support lymphocyte proliferation. The effect was not attributable to the physiological haemodilution of pregnancy leading to a reduced concentration of putative factors nor could transferrin levels or the iron binding capacity of this protein be implicated.

Adult↗
PubMed1989

Responses to mitogenic stimulation of lymphocytes taken during and after pregnancy.

Serial blood samples were collected during pregnancy, after delivery and several months postnatally from 28 women. The blastogenic responses of lymphocytes to varying concentrations of phytohaemagglutinin (PHA) were tested using autologous plasma or fetal calf serum (FCS) to support the lymphocyte cultures. Using FCS, the blastogenic response decreased as pregnancy progressed and remained depressed months after delivery. In contrast, when autologous plasma was used a 10-fold higher concentration of PHA was required to give optimal stimulation. Blastogenic responses were still suppressed during pregnancy but had returned to initial values by the time of delivery and were greater still in the post-partum and postnatal periods. We conclude that the inherent ability of lymphocytes to undergo blastogenesis is suppressed during pregnancy but that this is over-shadowed by a humoral effect of pregnancy plasma. The significance of these results is discussed.

Blood Physiological Phenomena↗
PubMed1989

Rapid early diagnosis of cytomegalovirus infection.

Cytomegalovirus infection can now be diagnosed rapidly in the laboratory by methods which are reviewed here. Together with the clinical investigation of patients early in their infection before extensive tissue damage has occurred, these methods offer the option of considering therapeutic intervention in some patients.

Antigens, Viral↗
PubMed1989

Fatal hepatitis B reactivation after autologous bone marrow transplantation.

We report a fatal case of hepatitis B reactivation following autologous bone marrow transplantation for acute lymphocytic leukaemia. The presence of antibodies to HBs and HBc at presentation indicated previous infection with hepatitis B; these antibodies disappeared during the course of treatment for leukaemia. HBsAg was first detected in serum 5 weeks post-transplant; liver function tests began to deteriorate 8 weeks later, when HBeAg was first detected. The hepatitis followed a fulminant course, and the patient died 10 days later, in the 15th week following transplant.

Adolescent↗
PubMed1988

Symptomatic cytomegalovirus infection in seropositive kidney recipients: reinfection with donor virus rather than reactivation of recipient virus.

74 patients receiving cadaver kidney grafts were investigated prospectively for cytomegalovirus (CMV) infection. Among seropositive recipients CMV infection, especially symptomatic and disseminated infection, occurred significantly more frequently when kidneys came from seropositive than from seronegative donors. Since seropositive recipients can become infected with donor virus, the excess is probably accounted for by reinfection. This conclusion was supported by restriction enzyme typing of virus isolates from recipient pairs receiving kidneys from the same donor; proven reinfection with donor strain virus was significantly commoner than proven reactivation of recipient virus. Furthermore, symptoms occurred only in the proven reinfection group. Although the proportion of reinfections that caused symptoms was less than that seen in primary infections, prior natural infection with CMV clearly does not prevent symptomatic reinfection in seropositive recipients, a point which has profound implications for future vaccination strategies in renal allograft recipients and choice of donors.

Cadaver↗
PubMed1988

Evaluation of eight and a half years of neonatal screening for haemoglobinopathies in Birmingham.

A pilot neonatal screening programme for haemoglobinopathies linked with screening for phenylketonuria and congenital hypothyroidism was reviewed. During 1978 to December 1986 137,000 neonates were tested. There were improvements in the detection rate and accuracy of diagnosis for homozygotes and mixed heterozygotes, mainly associated with the introduction of citrate agarose gel electrophoresis as a follow up procedure on all specimens showing any abnormality on the initial cellulose acetate electrophoresis. We recommend that the programme is continued on a service basis.

Anemia, Sickle Cell↗
PubMed1988

Presence of a partially acid-labile alpha-interferon in bronchoalveolar lavage fluid of patients with cytomegalovirus pneumonitis is associated with a poor prognosis.

In 30 patients with pneumonitis, 16 of whom had undergone bone marrow transplantation, 13 episodes of cytomegalovirus (CMV) pneumonitis were diagnosed. In three of these, alpha-interferon, which in two cases was partially acid-labile, was detected in bronchoalveolar lavage fluid. All three of these patients died. Only two deaths occurred in ten patients without detectable levels of alpha interferon in the lavage fluid. CMV pneumonitis in immunocompromised patients appears to stimulate the local production of a partially acid-labile alpha-interferon, and its presence is associated with a poor prognosis. Gamma-interferon was not found in the lavage fluid of any patient with pneumonitis.

Bone Marrow Transplantation↗
PubMed1988

Seroepidemiologic studies on the acquisition of antibodies to cytomegalovirus, herpes simplex virus, and human immunodeficiency virus among general hospital patients and those attending a clinic for sexually transmitted diseases.

A total of 731 sera were collected from general hospital patients, divided into five distinct subgroups, and tested for the presence of immunoglobulin (IgG) to cytomegalovirus (CMV) and herpes simplex virus (HSV). The results indicate a high level of association between the two viruses, although HSV was found to be more prevalent in the earlier years of life, whereas CMV was acquired constantly throughout life. An increase in age was also accompanied by significantly higher antibody levels to both viruses. Individuals with antibody to HSV were significantly more likely to have antibodies to CMV, suggesting that these viruses are transmitted by similar routes (?saliva). In addition, 430 sera from 94 homosexual and 336 heterosexual males attending a clinic for sexually transmitted diseases were tested for antibody to CMV, HSV, and human immunodeficiency virus (HIV). Homosexual males were more likely to have antibody to CMV and HIV than were heterosexuals, but no difference was seen for HSV antibodies. The levels of CMV-specific IgG were significantly raised in homosexuals, compared with heterosexuals, but again no difference was seen for HSV antibodies as in the general hospital patients, however, individuals with HSV antibodies were significantly more likely to possess antibodies to CMV. However, the additional association of CMV antibodies with a homosexual lifestyle suggests that an alternative route for acquisition of this virus exists (?semen). As raised levels of CMV antibodies, but not HSV antibodies, were found among homosexuals, this suggests that frequent CMV reinfections, rather than merely reactivation of latent herpes viruses, may be occurring.

Antibodies, Viral↗
PubMed1988

Enhancement of class I HLA antigen expression by cytomegalovirus: role in amplification of virus infection.

We have investigated the effect of cytomegalovirus (CMV) infection on the expression of class I HLA antigens on fibroblasts in vitro. Scanning and integrating microdensitometry was used to quantitate the level of cytoplasmic class I antigen expression, and an antibody binding assay was used to quantitate cell surface expression of class I HLA molecules. CMV infection resulted in a significant increase in the level of cytoplasmic and cell surface class I HLA antigen expression of fibroblast monolayers. The maximal effect was seen at 72 hours postinfection and was observed with both the laboratory strain of CMV, strain AD169, and with CMV purified directly from clinical specimens. Part of the increased HLA expression was mediated by interferon released from infected cells; however, an additional direct effect of the virus itself has not been ruled out. Interferon-induced increased expression of class I HLA antigens was accompanied by increased binding of CMV to the cells, consistent with our recent demonstration that class I HLA molecules can function as a cellular receptor for CMV.

Cells, Cultured↗
PubMed1988

Is the measurement of virus-specific antibody in the lungs of transplant recipients with cytomegalovirus pneumonitis of diagnostic or prognostic value?

We have investigated 12 transplant recipients (nine bone marrow transplants, three renal) with 15 episodes of pneumonitis caused by cytomegalovirus (CMV) and ten patients (eight bone marrow transplant recipients, two renal transplant recipients) with 12 episodes of interstitial pneumonitis in whom no CMV was detected, to determine whether levels of CMV-specific IgG in the lung are diagnostic of infection. We have also assessed whether a vigorous specific local antibody response is important for survival. CMV-specific IgG and herpes simplex (HSV)-specific IgG were measured in bronchoalveolar lavage (BAL) fluid and serum using albumin to correct for simple diffusion from serum into the lung. We have found evidence for local production or facilitated transport of CMV-specific IgG in ten patients with CMV pneumonitis but also in six patients with pneumonitis where no CMV was detected. Similar results were found for HSV-specific IgG although only one patient had a demonstrable HSV infection. There was a tendency for those patients producing large amounts of immunoglobulin in the lung to survive compared with those who died, but there were wide variations between patients in each group. The local humoral immune response in transplant patients with pneumonitis was not specific to the infecting agent and is most probably the result of polyclonal B cell activation or facilitated transport of IgG from serum to lung secretions. Measurement of CMV-specific IgG response in the lung should not, therefore, be used for diagnostic or prognostic purposes.

Adolescent↗
PubMed1988

Epidemiologic characteristics of cytomegalovirus infection in mothers and their infants.

In this longitudinal study of cytomegalovirus in 4578 pregnant women of middle/upper socioeconomic status in Houston, 52% had cytomegalovirus antibody when enrolled, and 48% were serologically susceptible. Studies were completed on 3899 mothers and their infants; 2.2% of these women experienced primary cytomegalovirus during pregnancy and 24% of those with primary infection transmitted cytomegalovirus to their infants. Of 22 cytomegalovirus-infected infants, 2 had disease at birth and 20 were asymptomatic. One symptomatic infant (primary maternal infection) has developmental delay. The other (immunocompromised mother with cytomegalovirus antibody before pregnancy) had hepatitis but has no symptoms at 1 year of age. On follow-up, 4 of 16 infants asymptomatic at birth have sequelae (hearing loss in 3, developmental delay in 1). All four were born to mothers with primary cytomegalovirus infection. Infant outcome was not related to trimester of maternal infection.

Antibodies, Viral↗
PubMed1988

Chronic cytomegalovirus infection.

Cytomegalovirus infects about 60% of persons in developed countries and may cause significant disease in immunosuppressed patients. Serology has no role in the diagnosis of CMV disease in such patients yet detection of the virus in diseased parts of the body can be used to monitor the course of disease and antiviral measures. Detection of viral proteins (alpha or beta proteins) by monoclonal antibodies in cell cultures infected by urine, saliva or blood samples from patients allows a positive diagnosis within 24 h (DEAFF test). Monoclonal antibodies against CMV can also be used to stain cells obtained directly from the infected patients.

Antibodies, Monoclonal↗