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P D Griffiths

Publications and source records attributed to P D Griffiths.

At least 181 records · Page 10Linked to original sources
PubMed1995

Longitudinal analysis of cytomegalovirus load in renal transplant recipients using a quantitative polymerase chain reaction: correlation with disease.

Serial surveillance samples of urine collected from 103 renal transplant recipients were analysed by polymerase chain reaction (PCR) for the presence of human cytomegalovirus (HCMV) DNA. The PCR results were consistently negative in 70 patients, none of whom developed HCMV disease, and PCR positive in 33 patients of whom 10 developed HCMV disease (P < 0.001). In 12 patients, PCR results were positive in three or more consecutive samples indicating extensive HCMV replication. HCMV load in 104 samples from these patients was analysed using a quantitative co-amplification PCR system. The maximal viral burden in the symptomatic patients ranged from 10(5.9) to 10(7.12) genomes/ml urine (median 10(6.5)) and in the asymptomatic patients from 10(4) to 10(5.7) genomes/ml urine (median 10(5.2)). The 10(1.3) difference between these median values was significant (P < 0.01). Individual kinetic profiles of viral burden showed that high levels of HCMV correlated with clinically apparent disease. In the majority of the asymptomatic individuals HCMV load remained between 10(4) and 10(5.1) genomes/ml urine; however, in two patients fluctuations in viral load were observed involving higher viral levels (up to 10(5.7) genomes/ml urine) suggesting that immune responses able to modulate viral replication could be studied in individual patients. Analysis of the temporal appearance and quantity of HCMV in the urine with alterations in white cell numbers showed that leukopenia occurred following the appearance of HCMV in the urine of symptomatic patients but preceded HCMV in the urine of asymptomatic patients (P = 0.01). Overall, these results show that longitudinal analysis using fully quantitative PCR methods for HCMV can provide insight into the natural history of HCMV disease in renal transplant recipients.

Adolescent↗
PubMed1994

Relation between human papillomavirus type 16 and potential for progression of minor-grade cervical disease.

We have previously reported that among 200 women referred for colposcopy with smears suggesting mild dyskaryosis, medium or high copy numbers of human papillomavirus type 16 (HPV16) DNA identified patients with current high-grade cervical disease. We have followed up 95 women from that group who had histologically proven mild-grade cervical disease (cervical intraepithelial neoplasia grade 1, n = 37) or wart virus infection (n = 12) or who had no evidence of cervical abnormality at study entry (n = 43). Kaplan-Meier survival analysis of the 70 months' follow-up was used to identify baseline features that might affect the risk of progression. 3 women were lost to follow-up; data were available for the remaining 92. Among the whole group the probability of remaining free of high-grade cervical disease was 0.71. Women with a histological diagnosis of minor-grade disease were more likely to progress to high-grade disease than those with no evidence of abnormality (proportion disease-free 0.52 vs 0.90, p = 0.004). Stratification of the group according to median age (28 years) revealed a weak association between age and disease progression (p = 0.04). There was no difference in disease-free probability between HPV16-positive and HPV16-negative women (0.75 vs 0.65, p = 0.19). Nor was there a significant difference in disease-free probability when the group was stratified by HPV16 viral burden. These data show that a histological diagnosis of minor-grade cervical disease is a better long-term predictor of disease progression than is HPV16 positivity, irrespective of copy number. These findings do not support the simple view that HPV16 alone is the cause of high-grade cervical disease, including cancer.

Adolescent↗
PubMed1994

HHV-6 in AIDS.

Explore the source record for details and available documents.

AIDS-Related Opportunistic Infections↗
PubMed1994

A detailed anatomical analysis of neurotransmitter receptors in the putamen and caudate in Parkinson's disease and Alzheimer's disease.

Autoradiography allows precise anatomical matching as well as quantification of receptor density and is an ideal procedure to investigate neurotransmitter receptor distribution. Post mortem tissue from the caudate and putamen was investigated in cases of Parkinson's disease, Alzheimer's disease and age matched controls. Autoradiography was used to determine benzodiazepine, muscarinic cholinergic, D1 and D2 dopamine receptor density in these regions. This work shows that within the control group there is significantly higher benzodiazepine receptor density in the medial portion of the caudate and putamen when compared to lateral region. In the caudate nucleus there is a 15% (not significant) decrease of these receptors from rostral to caudal, no such decrease was present in the putamen. Muscarinic and both D1 and D2 dopamine receptors were evenly distributed in the control cases. Significant abnormalities in Parkinson's disease included loss of benzodiazepine receptors in the mid and caudal portions of the putamen and a decrease in muscarinic receptor density in the rostral putamen in Parkinson's disease.

Alzheimer Disease↗
PubMed1994

Oculomotor nerve palsy due to thrombosis of a posterior communicating artery aneurysm following diagnostic angiography.

We present a patient who developed a painful third nerve galsy two days after angiography had demonstrated a large aneurysm on the P1 segment of the left posterior cerebral artery. CT at this stage demonstrated extensive thrombus within the previously uncomplicated aneurysm. The haemodynamics of this aneurysm resulted in incomplete clearance of contrast medium from its fundus and we posit that this may have promoted thrombus formation. Six months later the aneurysm was shown angiographically to be completely occluded.

Basilar Artery↗
PubMed1994

The radiological features of hemimegalencephaly including three cases associated with proteus syndrome.

We report the radiological appearances of 5 children with hemimegalencephaly. There are few reports of this rare condition in the radiological literature. Two of the children have hemimegalencephaly as an isolated finding while the other three have Proteus syndrome. Four children have seizures which commenced within the first 6 months of life and two of these subsequently required hemispherectomy. In addition to the typical radiological features of hemimegalencephaly there was a high incidence of other brain anomalies. These include hypoplasia of the corpus callosum and crus cerebri, grey and white matter calcification and cortical migration/organisational disorders.

Brain↗
PubMed1994

Thalamic infarction in childhood due to extracranial vertebral artery abnormalities.

We report two children who developed thalamic infarctions which were demonstrated by CT. Both children had apparently normal angiograms although the extra cranial portions of the vertebral arteries were not demonstrated on the initial examination. Subsequent angiograms demonstrated abnormalities of the cervical portion of the vertebral arteries, dissection and pseudoaneurysm in one case and a large fusiform aneurysm in the other. Both children made full neurological recoveries. The thalamus is supplied by branches from the vertebro-basilar circulation and it is important to study the entire length of the extra cranial vertebral arteries as well as the intracranial vasculature.

Adolescent↗
PubMed1994

Effects of high-dose oral acyclovir on herpesvirus disease and survival in patients with advanced HIV disease: a double-blind, placebo-controlled study. European-Australian Acyclovir Study Group.

OBJECTIVE: To determine the efficacy of high-dose oral acyclovir in preventing cytomegalovirus (CMV) and other herpesvirus disease in patients with advanced HIV disease and to evaluate its effect on patient survival. DESIGN: Double-blind, placebo-controlled randomized trial of up to 1 year's therapy. SETTING: Outpatient clinics in 16 hospitals in Europe and Australia. PARTICIPANTS: A total of 302 patients with Centers for Disease Control and Prevention stage IV HIV disease, seropositive for CMV and with CD4+ lymphocyte counts < or = 150 x 10(6)/l. INTERVENTIONS: Oral acyclovir (800 mg, four times daily) or matching placebo for 48 weeks. MAIN OUTCOME MEASURES: Time to development of CMV and other herpesvirus disease. Following the results of another study, the protocol was amended to make survival a second major endpoint. RESULTS: Acyclovir failed to reduce the incidence of CMV disease: the probability of developing CMV disease at 1 year was 0.24 and 0.23 in the placebo and acyclovir groups, respectively (P = 0.53). However, acyclovir significantly reduced the probability of dying at 1 year of follow-up (from 0.39 to 0.23; P = 0.018). As expected, acyclovir significantly reduced the incidence and frequency of herpes simplex virus disease. There were no notable differences between treatment groups in clinically adverse experiences and no changes in haematological parameters to indicate clinically significant drug-induced toxicity. CONCLUSIONS: High-dose acyclovir failed to reduce the incidence of CMV disease, but significantly reduced the probability of dying at 1 year of follow-up.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Transfer of humoral immunity against cytomegalovirus proteins following transplantation of T-cell-depleted allogeneic bone marrow from seropositive donors.

Previous work by Grob et al. [Lancet i: 774, 1987] has demonstrated that allogeneic, T-cell-depleted bone marrow transplant recipients have a better prognosis for reactivated cytomegalovirus (CMV) infection if their donor is also immune. It was proposed that adoptively transferred humoral immunity was responsible for the protective effect of active infection. Immunoblot analysis using purified virions was used here to examine pre- and posttransplant antibody responses of seropositive recipients who had undergone active viral infection after transplantation. Immunoblots were assessed for the numbers of polypeptides recognised and reactivity against individual polypeptides. Immunoblots were also scanned by quantitative densitometry, and the intensity of antibody responses against total viral protein and individual polypeptides was determined. Sera from recipients with immune donors exhibited a secondary-type immune response in terms of both intensity and polypeptide specific pattern of antibody reactivity, compared with those recipients with nonimmune donors. In particular, recipients with immune donors appeared to show a greater reactivity against a protein of M(r) 55,000; this may represent the envelope glycoprotein gB, which is a major target for neutralising antibodies, and might also be utilised for preparing an effective vaccine for CMV.

Antibodies, Viral↗
PubMed1993

Current management of cytomegalovirus disease.

Cytomegalovirus (CMV) is an important pathogen for the fetus, for allograft recipients, and for acquired immunodeficiency syndrome (AIDS) patients; the clinical features in each of these groups of patients are described. CMV may also act as a cofactor to accelerate the rate at which the human immunodeficiency virus (HIV) causes AIDS. Active CMV infection in immunocompromised patients is best managed by routine laboratory screening of patients at risk using assays that provide prognostic information. Antiviral therapy can then be considered under one of four headings: For prophylaxis, the drug is given to all patients from a particular time point, e.g., time of transplantation. Successful trials have been reported for interferon (renal transplant), acyclovir (renal transplant and bone marrow transplant), and ganciclovir (heart transplant and bone marrow transplant). For suppression, the drug is given once CMV excretion has been detected in peripheral sites of particular patients. A successful trial of ganciclovir in bone marrow transplant patients has been reported. For pre-emptive therapy, the drug is given once CMV has been detected systemically. A successful trial of ganciclovir in bone marrow transplant patients has been reported. Regarding treatment, a controlled comparison of ganciclovir and foscarnet for CMV retinitis in AIDS patients has shown that both drugs are equally effective but that foscarnet has a survival benefit. Open studies suggest that the combination of immunoglobulin and ganciclovir is of benefit for treatment of established CMV pneumonitis. In open studies other treatments have been tried, with no clinical success, despite control of viral replication in some cases.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1993

Future management of herpesvirus infections.

The clinical investigations conducted to date with herpesviruses have provided a good grounding into the general principles of herpesvirus replication and pathogenesis. Multiple opportunities for intervention include prevention of initial infection, prevention of reactivation, suppression of reactivated virus, and treatment of established disease. Studies have shown that each of these approaches can be effective against one or more herpesviruses. What is needed now are studies combining sequential interventions so that patients who fail, for example, prophylaxis with one drug can be entered directly into trials of suppression and then into pre-emptive therapy, each with different antiviral agents. In this way, it is to be hoped that increasing proportions of cohorts of susceptible patients will suffer less from herpesvirus infections. Clearly, the design of such clinical trials needs to be constantly refined as methods of diagnosis and understanding of pathogenic mechanisms improve and as new agents are discovered.

Antiviral Agents↗
PubMed1993

Prospective cytomegalovirus surveillance in paediatric renal transplant patients.

Fifty-eight consecutive paediatric recipients of 65 renal transplants were prospectively studied for up to 72 months for evidence of cytomegalovirus (CMV) infection. Blood, urine and saliva were screened for CMV pre transplant and then weekly for the first 6 weeks, and monthly thereafter, by conventional cell culture and by detection of early antigen fluorescent foci. Donor CMV serostatus was available in 51 cases. All patients received triple therapy as immunosuppression and none had CMV prophylaxis. Twenty-six episodes of CMV infection (40% of transplants) and 10 of CMV disease (15%) were identified. Donor CMV seropositivity, regardless of recipient CMV serostatus, was significantly associated with CMV infection (P = 0.04). First CMV excretion was significantly earlier in patients who subsequently became symptomatic than in those who did not (P = 0.04), and a positive blood culture was significantly associated with CMV disease (P = 0.04). We found no association between extra anti-rejection treatment or recipient's age and CMV infection or disease. CMV disease had no influence on renal function as assessed by glomerular filtration rate at 6, 12 and 24 months post transplant, nor on graft loss. CMV disease was fatal in 1 patient. We conclude that trials of CMV prophylactic agents are indicated, particularly in recipients of CMV seropositive grafts. A positive blood culture should lead to consideration of anti-CMV therapy.

Adolescent↗
PubMed1993

The use of effervescent agents in the small bowel meal examination.

Some perceived disadvantages of the small bowel meal examination are failure of adequate distension, lack of a double contrast effect and the duration of the procedure. A new use for effervescent granules during the small bowel meal is described which reduces the examination time by 70% and reduces the radiation dose to the patient.

Adult↗
PubMed1993

Use of semi-quantitative PCR for human papillomavirus DNA type 16 to identify women with high grade cervical disease in a population presenting with a mildly dyskaryotic smear report.

The aim of this study was to assess whether qualitative or semi-quantitative detection of human papillomavirus type 16 (HPV 16) can help to identify women with major grade cervical intraepithelial neoplasia (CIN 2 and CIN 3) among those referred with a smear suggesting mild dyskaryosis. The study population consisted of 200 women sequentially attending the Royal Free Hospital colposcopy clinic. All women were investigated by cytology, colposcopy and, where appropriate, histopathology, and HPV 16 DNA was detected in cervical scrape samples using the polymerase chain reaction (PCR). A final clinical diagnosis of normal, wart virus infected (WVI), CIN 1, CIN 2 or CIN 3 was made in 179 women. On the basis of the qualitative PCR data, the presence of HPV 16 DNA was of borderline use in identifying women with high grade cervical disease [63/113 (normal/WVI/CIN 1) vs 46/66 (CIN 2/CIN 3); P = 0.065]. However, semi-quantitative PCR analysis showed that a high/medium HPV 16 result was significantly associated with high-grade disease [29/113 (normal/WVI/CIN 1) vs 38/66 (CIN 2/CIN 3); P = 0.0001]. Furthermore, semi-quantitative PCR and cytology were performed on the repeat smear taken immediately prior to colposcopy. The combined laboratory results show that 53/60 women with biopsy proven high-grade disease were identified, as were 26/95 women who were either normal or who had low grade cervical disease. The possibility of using such an approach for selecting women for more rapid or for routine colposcopy appointments in the two groups respectively is discussed.

Adult↗
PubMed1993

Cytomegalovirus infection and risk of AIDS in human immunodeficiency virus-infected hemophilia patients. National Cancer Institute Multicenter Hemophilia Cohort Study Group.

The effects of prevalent and incident cytomegalovirus (CMV) infection on human immunodeficiency virus (HIV) disease progression were examined in 393 hemophilia patients with known dates of HIV seroconversion. Of the cases, 191 (49%) had IgG antibody to CMV in their earliest stored sera (median date, November 1983). CMV-seropositive subjects were one and a half times more likely to develop AIDS, and they were also older than CMV-negative subjects. Adjusted for age, CMV seropositivity was not associated with the development of AIDS. In age-adjusted analyses, CMV-seropositive subjects had a small, but statistically insignificant, decrease in survival after HIV seroconversion. Older subjects were more likely to CMV seroconvert by the time of their latest available serum samples (P = .03). CMV seroconverters were five times more likely to develop clinical CMV disease than were subjects initially CMV-positive (P = .02). To avoid this source of serious morbidity, CMV-seronegative hemophiliacs with HIV infection should not be exposed to cellular blood products or body fluids from CMV-seropositive donors.

Acquired Immunodeficiency Syndrome↗
PubMed1993

A clinico-pathological audit of opportunistic viral infections in HIV-infected patients.

OBJECTIVE: To determine the prevalence of opportunistic viral infections in multiple tissues at postmortems of HIV-infected patients, and to relate these findings to their antemortem clinical course. DESIGN: A study of viral infections in 16 tissues of HIV-positive postmortem cases, by a combination of histology and cell culture (virus isolation). Clinical details were abstracted retrospectively from patient records. PATIENTS: Forty-seven consecutive autopsies, performed between 1985 and 1992. SETTING: Autopsies were conducted by a single pathologist in a single London teaching hospital. RESULTS: Opportunistic viral infections were detected in 72% of all cases, comprising cytomegalovirus (CMV, 66%), herpes simplex virus (11%), JC virus (6%) and adenovirus (2%). The most commonly infected tissues were lung, adrenal, gastrointestinal tract and central nervous system, although all tissue sites sampled could potentially support viral replication. Of 464 tissues tested by both histology and cell culture, histology alone detected CMV in 45 tissues and cell culture alone detected CMV in 31 tissues. We determined that CMV detection in postmortem gastrointestinal tissues and central nervous tissue was significantly associated with antemortem undiagnosed diarrhoea and encephalitis, respectively. CONCLUSION: There is a high prevalence of opportunistic viral infections in late-stage HIV disease, which is best detected postmortem by the use of both histology and cell culture. Many of these infections correlate with undiagnosed symptoms antemortem. The ability of sensitive methods for virus detection to alert the clinician to such cases antemortem should be critically evaluated, as should attempts to influence the natural history of these infections by antiviral drugs. Continuing clinico-pathological audit is important for AIDS patients in order to monitor the impact of known opportunistic viral infections and to identify others which may emerge as immunosuppression becomes more profound.

AIDS-Related Opportunistic Infections↗