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P D Griffiths

Publications and source records attributed to P D Griffiths.

At least 199 records · Page 11Linked to original sources
PubMed1993

The prognostic significance of positive CMV cultures during surveillance of renal transplant recipients.

Renal transplant recipients are at risk of severe morbidity and mortality from CMV disease. We have undertaken routine surveillance for CMV shedding on 133 transplant recipients, using a rapid culture technique, in order to assess the incidence of CMV infection and disease in these patients and to assess the prognostic significance of detection in whole blood, throat swab specimens, or urine. Donor CMV seropositivity was associated with posttransplant CMV infection (P < 0.05) and disease (P = 0.06). CMV infection and disease were associated with the receipt of anti-T-cell antibodies (P < 0.0001 and P = 0.08, respectively). First shedding of virus from any site occurred earlier posttransplant in those recipients who developed disease (median 39 days) than in those who did not (median 55 days)(P < 0.05). Detection of virus in blood occurred at a median time of 16 days before onset of symptoms, compared with 9 days before symptoms in urine, and 3 days after onset of symptoms from throat swab. A positive blood culture represented a relative risk of 7.1 for the subsequent development of disease, compared with 2.1 and 1.8 for positive urine and saliva cultures, respectively. The addition of urine cultures to blood cultures increased the sensitivity for identification of those at risk--however, the relative risk was reduced to 5.8. We conclude that routine surveillance for CMV shedding, especially in blood and urine, can identify recipients at high risk of CMV disease, and propose a trial in which those with asymptomatic viremia are allocated to receive ganciclovir or placebo, in order to assess the efficacy of "preemptive" therapy in this group of patients.

Antilymphocyte Serum↗
PubMed1993

Provision of prognostic information in immunocompromised patients by routine application of the polymerase chain reaction for cytomegalovirus.

A polymerase chain reaction (PCR) assay that amplifies a 149 base pair fragment of the cytomegalovirus glycoprotein B gene was used in the routine screening of 548 urine and 248 blood specimens from immunocompromised patients. The PCR results were compared with those obtained for the same specimens tested by the methods of conventional cell culture (CCC) and detection of CMV-specific immediate-early antigen fluorescent foci (DEAFF). For both urine and blood, PCR positivity correlated with a positive result in CCC (urine 93.2%; blood 86%). As expected for a more sensitive assay, PCR also identified CMV in samples that were negative by CCC and DEAFF such that there was no concordance between tests (Kappa test P > 0.05). The sensitivity, specificity, positive predictive value, and negative predictive values of PCR positivity in blood with respect to CMV disease were 0.8, 0.86, 0.62, and 0.94, respectively, with an associated relative risk of 5.84 (95% CI; 3.2-10.8). PCR detection of CMV in urine was more sensitive than either DEAFF or CCC (0.6 vs. 0.35 and 0.5, respectively) and had a high negative predictive value (0.89) but the positive predictive value was lower than either CCC or DEAFF (0.32 vs. 0.41 and 0.37, respectively) with respect to disease. Longitudinal data on patients with disease showed that CMV in blood was detected at a median of 5 days (range; -20 to +3 days) before disease onset whereas CMV was detected by CCC at a median of 13 days (range -4 to +20 days) after disease onset. In addition, the PCR assay was integrated into the battery of tests routinely performed on transplant patients in the diagnostic laboratory at this institution.

AIDS-Related Opportunistic Infections↗
PubMed1993

The adequacy of cervical spine radiographs in the accident and emergency department.

One hundred and twenty radiographs of the cervical spine were performed at the request of the Accident and Emergency (A & E) department over a 6 week period. These consecutive films were reviewed for adequacy of anatomical demonstration of the complete cervical spine. The initial series of three films presented to the A& E staff achieved this objective in only 55% of cases overall, although further radiographic examinations requested before the patient left the department raised this figure to 75% for the lateral view and to 70% for the combined anteroposterior (AP) views. From the data it can be predicted that if every patient whose first 3 films were inadequate had received further investigation, the cervical spine would have been well visualized on approximately 90% of radiographs in each plane. The availability of radiologists for advice and their involvement with senior A & E staff in teaching are important factors in improving this situation.

Adolescent↗
PubMed1993

Value of routine surveillance cultures for detection of CMV pneumonitis following bone marrow transplantation.

The results of 5018 surveillance cultures for the detection of cytomegalovirus (CMV) from 177 patients undergoing allogeneic T cell-depleted bone marrow transplantation (BMT) were analysed to determine their value in predicting future development of CMV pneumonitis. Twenty-two patients were diagnosed as having CMV pneumonitis. The median times of a positive CMV culture result from urine, saliva or blood before disease in these patients were 32, 8 and 23 days, respectively. The positive predictive value of CMV viraemia for the development of CMV pneumonitis was 0.64. Multivariate analysis showed that recipient pretransplant CMV seropositivity and increasing recipient age were independent risk factors for CMV pneumonitis. By contrast, donor CMV seropositivity was protective against disease, supporting the hypothesis that immunity against CMV can be adopted from donor T cell-depleted marrow. It is concluded that detection of CMV viraemia in a surveillance protocol can predict subsequent CMV pneumonitis but that it is of low sensitivity. This might be improved by more frequent sampling or by the use of a more sensitive assay, such as the polymerase chain reaction, thus identifying individuals who may benefit from 'pre-emptive' therapy.

Antibodies, Viral↗
PubMed1992

Parvovirus B19 outbreak in a children's ward.

Parvovirus B19 infection can cause severe complications in pregnant women, individuals with haemolytic anaemia, and those who are immunocompromised. In a hospital outbreak of this infection, a balance should be struck between protection of these individuals and the maintenance of medical services. The index case of an outbreak of parvovirus B19 infection among staff and patients of a paediatric ward was not identified. 58 members of staff were screened for B19 markers and 4 of the 6 susceptible men and 6 of the 24 susceptible women became infected (p = 0.05) as defined by serum IgM and viraemia. 1 of the 11 adults (10 members of staff and 1 parent) infected remained symptom-free. 12 immunocompromised patients were also assessed, and symptom-free infection developed in 2 of these. During the outbreak staff with symptoms were put on sick leave, immunocompromised patients (there were none with haemolytic anaemia) were given normal human immunoglobulin and nursed in single rooms by B19 IgG-positive, IgM-negative staff, and the ward was closed to B19 IgG-negative pregnant women. However, the limitation of spread of infection cannot be attributed with certainty to the measures taken.

Adult↗
PubMed1992

Comparison of cervical cytology and the polymerase chain reaction for HPV 16 to identify women with cervical disease in a general practice population.

A comparison of the ability of cervical cytology and the polymerase chain reaction (PCR) for human papilloma virus type 16 (HPV 16) to identify women with cervical disease has been performed in a general practice population of 249 women, none of whom were believed to have current cervical disease prior to examination. Within this population, 29 women were found by colposcopy and subsequent histopathology to have evidence of cervical disease [5 with cervical intraepithelial neoplasia (CIN) 3; 8 with CIN 2; and 16 with CIN 1]. The prevalence of HPV 16 in this population was 18.9% (CIN 3, 80%; CIN 2, 50%, CIN 1, 12.5%, normal, 16.8%). Women with severe disease (CIN 2 and CIN 3) had a significantly higher incidence of HPV 16 DNA than those with mild cervical disease (CIN 1) or no cervical abnormality (P = 0.001). There was no significant difference in the ability of either PCR for HPV 16 or cytology to identify women with cervical disease. The combination of screening by cytology and the presence of HPV 16 DNA resulted in the identification of a higher proportion of the women with disease, but this observation did not reach statistical significance. Although the failure to detect disease by the two screening methods was similar, HPV 16 DNA positivity was associated with a higher false-positive rate for disease detection than cytology (P less than 0.03). The PCR assay for detecting HPV 16 in this investigation was shown to have a false-positive rate of 2.4% and a false-negative rate of 10.4%. The prospect of screening women for cervical disease using PCR for HPV 16 is discussed.

Adolescent↗
PubMed1992

Risk factors for viral reactivation following bone marrow transplantation.

The identification of risk factors for viral reactivation following transplantation is essential in order that antiviral prophylactic regimes may be allocated rationally. In the pretransplant period qualitative serological assessment of recipient and donor is informative with regard to the risk of post-transplant reactivation and disease. In addition, the quantitative level of herpes simplex virus (HSV) IgG in the pretransplant recipient is predictive of post-transplant HSV excretion, although this relationship does not exist for other viruses of the herpes group. We discuss the value of surveillance cultures for cytomegalovirus in the post-transplant period in predicting the development of CMV disease, and how this may allow effective intervention to prevent what is a major cause of morbidity and mortality in the transplant population.

Antibodies, Viral↗
PubMed1992

Detection of cytomegalovirus by a rapid culture system: a comparison of monoclonal antibodies in a clinical setting.

A monoclonal antibody cocktail, directed against immediate early antigens of cytomegalovirus, was assessed in a rapid culture system for detection of CMV (DEAFF) in clinical samples. The antibody cocktail was shown to be equivalent in sensitivity and specificity to our currently used monoclonal antibody. A comparison of DEAFF (using either monoclonal preparation) and conventional cell culture shows that DEAFF detects a smaller proportion of CMV positive samples from those receiving antiviral chemotherapy. The reasons for the discrepancies observed between these techniques are discussed.

Antibodies, Monoclonal↗
PubMed1992

Double-blind, placebo-controlled trial of human lymphoblastoid interferon prophylaxis of cytomegalovirus infection in renal transplant recipients.

We have conducted a double-blind, placebo-controlled trial of human lymphoblastoid interferon prophylaxis of cytomegalovirus (CMV) infection in 74 renal transplant recipients. Interferon (3 x 10(6) units was given thrice weekly for the first 6 weeks, then twice weekly for a further 8 weeks. During the period of interferon therapy, the incidence of CMV excretion was lower in the interferon group (28% versus 50%, P = 0.065), mainly due to a significant reduction of CMV reactivation (9% versus 56%, P = 0.02). However, for the whole study period (including the follow-up period after interferon therapy), there was no difference in the incidence of CMV excretion (44% versus 53%). The onset of CMV excretion was delayed (8.2 +/- 0.8 to 20.9 +/- 5.5 weeks, P = 0.04). The duration of CMV excretion was also reduced (11.1 +/- 3.1 to 29.4 +/- 5.7 weeks, P = 0.008). The number of positive CMV isolates from urine and saliva was significantly less in the interferon group. There was no difference in the site of CMV excretion. Of the patients in the treatment group who excreted CMV, 43% developed disease as compared to 63% in the control group (difference not significant). There was also no significant difference in the severity of the CMV infection between the two groups. Benefit appears to be restricted to seropositive recipients of seronegative kidneys. The interferon regime used in this study was well tolerated, with mild fever being the only reported side-effect. No patient had to stop therapy because of toxicity. The incidence of rejection and graft loss was not different between the two groups.

Adult↗
PubMed1992

Relationship between herpes simplex virus ulceration and CD4+ cell counts in patients with HIV infection.

OBJECTIVE: To establish the incidence of herpes simplex virus (HSV) ulceration in relation to CD4+ cell counts in HIV-infected patients. DESIGN: Swabs were taken from all ulcerated lesions in HIV-infected patients and cultured for HSV. CD4+ cell counts were performed at regular intervals. SETTING: The HIV unit at a London teaching hospital (the Royal Free Hospital, London, UK). PATIENTS: All HIV-infected patients (n = 500) attending the HIV unit. RESULTS: Two hundred and twenty-three swabs were obtained from 118 patients; 83 (37.2%) swabs from 62 (52.5%) patients were positive for HSV. Of 96 swabs taken from patients with CD4+ cell counts < 50 x 10(6)/l, 56 (58.3%) were positive for HSV, compared with 27 of 127 (21.2%) swabs from patients with higher CD4+ cell counts (P < 0.0001). Of patients with CD4+ cell counts < 50 x 10(6)/l, 37 of 47 (78.7%) had positive cultures compared with 25 of 71 (35.2%) of patients with higher counts (P < 0.0001). This trend was observed with swabs from all body sites; sufficient samples were available from oral and perianal lesions to demonstrate statistical significance (P < 0.0001 and P = 0.007, respectively). CONCLUSIONS: These results show a sharp rise in the incidence of HSV with CD4+ cell counts < 50 x 10(6)/l and thus provide important data for the design of studies of anti-HSV prophylaxis. Furthermore, since nearly 60% of all ulcers in patients with such low CD4+ counts are HSV-positive, we suggest appropriate empirical therapy on presentation.

AIDS-Related Opportunistic Infections↗
PubMed1992

Surveillance for CMV infection in orthotopic liver transplant recipients.

Infection with cytomegalovirus is a major cause of morbidity and mortality following orthotopic liver transplantation. In order that preventive strategies may be devised, a detailed assessment of risk factors for infection and disease is required. We have prospectively assessed 46 orthotopic liver transplant recipients for CMV excretion from multiple sites in order to determine incidence of, and risk factors for, CMV infection and disease. Risk factors for posttransplant CMV infection were donor CMV seropositivity, an increased volume of peritransplant whole-blood transfusion and an increased dose of extra steroid therapy to treat rejection episodes. These findings implicate, respectively, transfer of virus with donor organ, transfer of virus with blood transfusion, and stimulation of reactivation of latent virus in recipients through augmented immunosuppression. The possible ways of preventing or ameliorating these effects are discussed.

Adult↗
PubMed1992

Quantification of human cytomegalovirus DNA using the polymerase chain reaction.

The important goal of developing quantitative assays for viral nucleic acids in clinical samples has been achieved for human cytomegalovirus (HCMV) by using a modified polymerase chain reaction (PCR). A control PCR target sequence was constructed by PCR mutagenesis to allow the post-amplification quantification of HCMV DNA. The control region was identical to a naturally occurring sequence within the glycoprotein B (gB) coding part of the virus genome, except that a unique restriction site, introduced by the aforementioned mutagenesis step, allowed post-amplification differentiation of control/non-control target amplified product. This technique was initially validated using known amounts of cloned control/non-control target DNA, and was found to be sufficiently sensitive to allow the quantification of a range of 10 to 10(6) genome equivalents of virus. The method was applied to urine samples of congenitally infected infants for which infectious virus titres were available. The results obtained demonstrated that the number of infectious virions determined by conventional cell culture represented a small proportion of the HCMV genome present in the samples, as assessed by the quantitative PCR methodology.

Base Sequence↗
PubMed1992

Cytomegalovirus (CMV) infection, CD4+ lymphocyte counts and the development of AIDS in HIV-1-infected haemophiliac patients.

After a maximum of 11 years (median 8.3 years) from the time of HIV seroconversion, 25 out of 59 (42%) of CMV-seropositive haemophiliacs had progressed to AIDS, as opposed to eight out of 50 (16%) CMV seronegatives. The age-adjusted relative risk for AIDS among CMV seropositives was 2.4 (P = 0.03). In order to determine how this adverse effect is mediated, the mean rate of decline in serial CD4+ lymphocyte counts was studied. CD4+ lymphocyte counts tended to decline more rapidly in CMV seropositives than in seronegatives (-0.087 x 10(9)/l per annum versus -0.082 x 10(9)/l per annum), but this difference did not reach statistical significance. The average CD4+ lymphocyte count at the time of HIV seroconversion was estimated to be similar in CMV seropositives and negatives, because in HIV-1-negative haemophiliacs the CD4+ counts were virtually identical, after adjustment for age (0.94 x 10(9)/l and 0.97 x 10(9)/l, respectively). The median CD4+ cell count at which AIDS developed was higher in the CMV-seropositive group (0.07 x 10(9)/l) than in the seronegative group (0.04 x 10(9)/l), but this difference did not reach statistical significance. We conclude from these findings that the adverse effect of CMV is not wholly mediated via a more rapid loss of CD4+ cells. We discuss other processes that may be mediated by CMV, such as a functional deficiency of residual CD4+ cells, or dissemination of HIV in other organs, which may be important in determining the earlier onset of AIDS among CMV-seropositive subjects.

Acquired Immunodeficiency Syndrome↗
PubMed1992

JC virus associated meningoencephalitis in an immunocompetent girl.

JC virus is most commonly acquired during childhood, and no clinical illness has been associated with primary infection, which is assumed to be asymptomatic. The only disease associated with JC virus to date is progressive multifocal leucoencephalopathy (PML), which is usually caused by viral reactivation in immunocompromised adults. A chronic meningoencephalitis associated with an active JC virus infection in an immunocompetent 13 year old girl is described.

Adolescent↗
PubMed1992

Severe cytomegalovirus pneumonitis in HIV infected patients with higher than average CD4 counts.

BACKGROUND: Cytomegalovirus may replicate within the lungs both of recipients of transplants and of patients infected with the human immunodeficiency virus (HIV). A hypothesis formulated by this group was that a host damaging immune response might be provoked by cytomegalovirus infection and cause a severe pneumonitis in recipients of allogeneic transplants, whereas the progressive impairment of cellular immunity in patients with HIV disease would preclude a damaging immune response in the lungs, and thus protect these patients from severe cytomegalovirus pneumonitis. This study set out to discover whether severe cytomegalovirus pneumonitis arises in HIV infected patients. METHODS: Data were prospectively collected on severity of pneumonitis and infectious agents identified in consecutive respiratory episodes in HIV infected patients undergoing diagnostic bronchoalveolar lavage during 20 months. RESULTS: Eighty five episodes of pneumonitis occurred in 68 patients. Cytomegalovirus was identified as the only infectious agent in nine episodes (nine patients). Seven of the episodes were mild; all these patients had CD4 counts below 0.1 x 10(9)/1. The remaining two episodes were severe and ventilatory support was required. In both cases the CD4 counts were above 0.2 x 10(9)/1 and HIV infection appeared to have been acquired shortly before presentation. CONCLUSION: Although rare, severe cytomegalovirus pneumonitis may occur in HIV infected patients. Both patients with severe pneumonitis in this series had relatively well preserved immune function. These findings support the hypothesis that severe cytomegalovirus pneumonitis is an immunopathological condition.

Adult↗
PubMed1992

Studies to define viral cofactors for human immunodeficiency virus.

Results from molecular biologic, cell biologic and animal experiments show that HIV replication can be driven by a variety of other viruses. If such interactions took place in vivo, then they could help to explain some of the complex pathogenesis of AIDS. The problems incurred in attempting to address this question in populations of humans are discussed.

AIDS-Related Opportunistic Infections↗