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Biomedical subjects

D Jeffries

Publications and source records attributed to D Jeffries.

At least 19 recordsLinked to original sources
PubMed1999

Use of molecular assays in diagnosis and monitoring of cytomegalovirus disease following renal transplantation.

We compared two commercial molecular assays (the Murex Hybrid Capture CMV DNA assay [HCA], version 2, and the Roche Amplicor plasma PCR assay) with a standard shell vial assay in detecting and predicting cytomegalovirus (CMV) disease in a group of renal transplant patients and assessed the role of viral load measurements (using the HCA) in their management. The sensitivity of the HCA and Amplicor assay in terms of disease detection was 100%, compared to 71% for the shell vial assay. Both the HCA and the PCR assay detected all cases of disease, at medians of 11 and 12.5 days before the onset of symptoms, respectively. Significantly higher viral loads were detected in those patients with symptoms (7.9 x 10(5) copies/ml) than in patients without symptoms (7.9 x 10(4) copies/ml; P < 0.0001). There was also a trend towards higher viral loads in those patients with primary infections (7.8 x 10(5) copies/ml) than in those patients with reactivations of CMV disease or reinfections. Successful treatment with ganciclovir was associated with a >90% reduction in viral load. Both of these new assays are sensitive and easy to use. A comparison of accurate quantitation is also useful in monitoring responses to antiviral therapy.

Adult↗
PubMed1998

BCL-2 expression correlates with lower proliferative activity in the intermediate- and high-grade non-Hodgkin's lymphomas: an Eastern Cooperative Oncology Group and Southwest Oncology Group cooperative laboratory study.

An inverse relationship between BCL-2 expression and cell cycle transition has been suggested by recent studies in murine models. To investigate the clinical relevance of these laboratory studies, a group of 116 paraffin-embedded non-Hodgkin's lymphoma (NHL) biopsy specimens (Working Formulation Groups D-H, and J) from a cooperative group study of cellular DNA content were analyzed for the 14;18 translocation using polymerase chain reaction (PCR)-based methods and, if sufficient tissue remained, for BCL-2 and BAX expression by immunohistochemistry. The results of these studies were then compared with the results of the previously performed flow cytometric analysis of ploidy and proliferative activity (S-phase-fraction). BCL-2 expression was inversely associated with proliferative activity (P = .001; n = 41), but there was no association between staining for Bax and %S-phase. Ploidy was not associated with either BCL-2 or BAX expression. The t(14;18) was detected in 21 of the 54 cases in which PCR-amplifiable DNA was recovered; 20 of these occurred at the major breakpoint region and 1 at the minor breakpoint region. High levels of BCL-2 or BAX expression occurred independently of t(14;18). There was no association between t(14;18) and either ploidy or proliferative activity. The inverse relationship between BCL-2 expression and proliferative activity in the intermediate- and high-grade NHLs is consistent with recent studies suggesting that Bcl-2 both retards entry into the cell cycle and inhibits apoptosis.

Cell Division↗
PubMed1998

Evaluation of specific herpes DNA viruses in idiopathic megarectum and idiopathic megacolon.

PURPOSE: The aetiology of idiopathic megarectum and idiopathic megacolon is unknown. A previous study in patients with chronic idiopathic intestinal pseudo-obstruction, a condition also associated with a dilated gut, identified the possible involvement of herpes viruses. This study therefore aimed to determine whether these viruses may also be implicated in the pathogenesis of these conditions. METHODS: Resected large bowel from three patients with idiopathic megarectum and three patients with idiopathic megacolon were studied. Histology for viral inclusions and nested polymerase chain reaction (PCR) using specific primers for cytomegalovirus, Epstein-Barr virus, herpes simplex virus type 1 and varicella zoster virus was performed. DNA was extracted from paraffin-embedded blocks by proteinase K and phenol chloroform extraction. RESULTS: Viral inclusions were not seen. PCR failed to identify DNA of the four herpes viruses tested. CONCLUSION: Patients with idiopathic megarectum or idiopathic megacolon may have subtle abnormalities of the enteric innervation, but these do not appear to be attributable to the neurotropic effects of the herpes viruses studied.

Cytomegalovirus↗
PubMed1998

Comparison of culture- and non-culture-based methods for quantification of viral load and resistance to antiretroviral drugs in patients given zidovudine monotherapy.

Virological assays for human immunodeficiency virus type 1 load and drug resistance can broadly be divided into culture-based and molecular biology-based methods. Culture-based methods give a direct measure of infectious virus load and phenotypic drug resistance, whereas molecular biology-based methods are indirect, assaying nucleic acid levels to determine virus load and point mutations associated with drug resistance. We have compared culture-based and non-culture-based methods for patients enrolled in a placebo-controlled trial of zidovudine (the Concorde Trial). Virus loads were assayed by culture of peripheral blood mononuclear cells (PBMCs) or quantitative PCR, and drug resistance was assayed in culture or in a quantitative, PCR-based point mutation assay. The rates of detection of viremia and drug resistance were higher by PCR than by culture for this population of subjects. Comparison of the virus loads by the two measures showed a good correlation for virus loads in PBMCs but a poor correlation for virus loads in plasma. The latter result probably reflected the inaccuracies of culture in assaying plasma with the low infectious virus titers seen in the study population. The concordance of phenotypic and genotypic drug resistance methods was high, with all phenotypically resistant isolates having at least one resistance-associated mutation and with no mutations being found in a drug-sensitive isolate. Genomic resistance scores (weighted sums of levels of resistance mutations) showed good correlations with the levels of phenotypic resistance, and both resistance measures were observed to increase as the duration of exposure to drug increased. Overall, non-culture-based methods were shown to correlate well with culture-based methods and offer a low-cost, high-throughput alternative. However, culture-based methods remain the final arbiters of infectious virus load and phenotypic drug resistance and are unlikely to be superseded entirely.

Acquired Immunodeficiency Syndrome↗
PubMed1997

HIV-1 viral load, phenotype, and resistance in a subset of drug-naive participants from the Delta trial. The National Virology Groups. Delta Virology Working Group and Coordinating Committee.

BACKGROUND: The Delta trial showed that combination therapy (zidovudine plus didanosine and zidovudine plus zalcitabine) substantially lengthened life and reduced disease progression compared with zidovudine monotherapy. We did a nested virological study in three countries (France, the Netherlands, and the UK) to investigate changes in markers for viral load and antiretroviral-drug resistance during therapy. METHODS: 240 zidovudine-naive HIV-1-infected patients were randomly assigned zidovudine only (n = 87), zidovudine plus didanosine (n = 80), or zidovudine plus zalcitabine (n = 73). Viral load in peripheral-blood mononuclear cells and plasma was measured by quantitative culture. Plasma HIV-1 RNA was measured by reverse-transcriptase PCR amplification, and serum p24 antigen by ELISA. Resistance to antiretroviral drugs was measured phenotypically by culture and genotypically by detection and quantification of drug-related point mutations in the pol gene. Analyses were done by intention to treat. FINDINGS: The reduction in viral load was greatest 4-12 weeks after the start of therapy and was most pronounced in the combination-therapy study groups (median reductions of RNA at 4 weeks 1.58, 1.28, and 0.49 log10 copies/mL for zidovudine plus didanosine, zidovudine plus zalcitabine, and zidovudine only, respectively). RNA levels at 8 weeks were predictive of disease progression and death after allowance for baseline values. At 48 weeks, the proportion of participants with phenotypic zidovudine resistance was similar in all three groups: didanosine and zalcitabine resistance were rare; zidovudine genomic resistance correlated with phenotypic resistance (r = 0.54, p < 0.0001) and developed earlier in the combined-therapy groups. However, participants in the zidovudine monotherapy group had higher circulating loads of resistant virus than those in the combined-therapy groups. INTERPRETATION: Combined antiretroviral therapy was more efficient at lowering virus load than monotherapy. Although zidovudine resistance was common in monotherapy and combined-therapy groups, circulating concentrations of resistant virus were substantially lower in the combination groups, which is likely to be a result of the continued antiviral activity of didanosine or zalcitabine.

Anti-HIV Agents↗
PubMed1997

Is HTLV-1 status another antenatal screening test that we need?

Human T-lymphocytic virus type 1 (HTLV-1) carriage is associated with a 2% to 5% lifetime risk of developing a severe, if not fatal, disease. In our Inner London antenatal population, we found that the carrier rate was 0.3%. The antenatal transmission rate is known to be very low, but if the infant is breastfed the transmission rate is up to 25%. It is therefore possible to interrupt the transmission cycle by advising against breastfeeding. The ethical and fiscal issues surrounding antenatal testing are addressed.

Enzyme-Linked Immunosorbent Assay↗
PubMed1994

Risk identification for HIV infection in an inner London antenatal population.

This study was carried out to ascertain whether routine antenatal history taking is an effective means of identifying risk factors for HIV infection. Information about risk obtained at routine booking was compared with answers to selected questions obtained at a research interview. The study was conducted at St. Bartholomew's Hospital Homerton, and ran from February 1991 to March 1992. Of the 3729 women interviewed, 1671 had been hand booked (unstructured questionnaire) and 2058 had been computer booked (structured questionnaire). Hand booking failed to identify 77% of risk factors compared with 7% for computer booking. The findings highlight the underdetection of risk activity and confirm the need for intermittent, anonymous sampling to obtain background information against which a decision to implement universal testing may be made.

Female↗
PubMed1990

Phase II study of 10-ethyl-10-deaza-aminopterin (10-EdAM; CGP 30 694) for stage IIIB or IV non-small cell lung cancer.

Thirty-one patients with stage IIIB or IV non-small cell lung cancer (NSCLC) were treated with intravenous 10-EdAM on a weekly basis. The starting dose was 80 mg/m2, with subsequent doses adjusted depending on evidence of toxicity. There were 20 men and 11 women with a median age of 58 years (range, 33-75). Response was evaluated in 30 patients, 5 with evaluable but not measurable tumors and 25 with measurable indicator lesions. There were no complete remissions; 3 patients achieved partial remission. Nine patients had a minor response, 6 showed no change, and 12 had progressive disease. Median survival for all 31 patients was 43 weeks (range, 12-65+). During the first 3-week period, the 10-EdAM dose was reduced or withheld in 19 patients (because of stomatitis in 12, SGPT elevation in 3, skin rash in 2, and granulocytopenia in 2), escalated in 11 patients, and unchanged in 1 patient. A mean of 34-88 mg/m2 of 10-EdAM (median, 50) was given per week during the first 5-week period. Myelotoxicity was infrequent and there was no significant nephrotoxicity. Considering the modest side effects of this treatment and the conservative dose-modification schedule which mandated substantial dose reductions, we conclude that 10-EdAM is a promising antitumor agent for NSCLC.

Adult↗
PubMed1990

Phase II study of 4-demethoxydaunorubicin in previously untreated extensive disease non-small cell lung cancer.

Fifteen patients with previously untreated extensive non-small cell lung cancer (E-NSCLC) were treated with oral 4-demethoxydaunorubicin (4-DMDR) at the dose of 10 mg/m2/day x 5 days every 3 weeks with routine administration of antiemetic drugs. They received a median of two courses of treatment with the cumulative dose range from 50-712.5 mg/m2. One patient achieved partial remission with a duration of 14 weeks. Two patients had minor responses with durations of 14 and 24 weeks. Stable disease occurred in three patients (21, 22, and 27 weeks). Median survival was 33 weeks (range 3-73+ weeks). Toxicities were tolerable. Neutropenia (less than 1,000 mm3) occurred in only 16% of all treatment courses. Three patients developed correctable arrhythmias (two with atrial fibrillation and one with accelerated junctional rhythm). The cause of arrhythmia was unclear. No clinical evidence of congestive heart failure or decreased cardiac ejection fraction was observed. Nausea and vomiting were common but tolerable. Alopecia and mucositis were uncommon. Clinical pharmacokinetic studies were done in nine patients. However, plasma 4-DMDR levels were below the limit of detection (3 ng/ml). Because 4-DMDR has shown some activity in previously untreated E-NSCLC and the toxicities at this dose schedule are mild, we suggest that further studies of this drug at a higher dose in this schedule are indicated.

Adult↗
PubMed1990

Ifosfamide with mesna uroprotection in the management of lung cancer.

Fourteen patients with extensive disease small cell bronchogenic carcinoma (SCBC) received ifosfamide at 2,000 mg/m2/day for 5 consecutive days with simultaneous mesna and vincristine while 26 patients with extensive disease non-small-cell bronchogenic carcinoma (N-SCBC) received the same regimen without vincristine. Eight partial responses (57%) were observed with a 40-week median survival in the case of SCBC and four partial remissions (15%) with a 31-week median survival in N-SCBC. Granulocytopenia was the dose-limiting toxicity, whereas urotoxicity was well controlled with mesna. Neuropsychiatric toxicity consisted of anxiety, agitation, confusion, and hallucination. Neurobehavioral testing detected worsened performance during ifosfamide treatment. Ifosfamide is one of the few active agents in N-SCBC.

Aged↗
PubMed1989

Phase II study of idarubicin in extensive-disease non-small-cell lung cancer.

Fourteen patients with extensive-disease non-small-cell lung cancer (E-NSCLC) were treated with oral 4-demethoxydaunorubicin (idarubicin, 4DMDR) at a dosage of 10 mg/m2/day x 5 days every 3 weeks. The median cumulative dose was 110 mg/m2 (range: 50-1,100). Two patients had stable disease for 12 and 56 weeks, respectively, one patient had failed to respond to a doxorubicin hydrochloride (Adriamycin)-containing regimen, and one had had no prior therapy. Twelve of the 14 patients had prior radiotherapy, chemotherapy, or both. Median survival for this heavily treated group was 16 weeks. Myelosuppression was minimal. Nausea and vomiting occurred in 44% of all courses. No cardiac toxicity and no decrease in cardiac ejection fraction was observed. We conclude that 4DMDR is ineffective in heavily treated E-NSCLC patients. However, the drug's activity in untreated patients is unknown. Further study of 4DMDR is indicated in patients who have had no prior chemotherapy or radiotherapy, with routine administration of antiemetic drugs along with pharmacokinetic studies.

Adolescent↗
PubMed1988

Acute meningo-encephalitis on dose reduction of zidovudine.

In a study of treatment by zidovudine in 106 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex, an acute meningo-encephalitic illness developed in 4 of 21 patients within 17 days after the dose of zidovudine had had to be reduced because of myelotoxicity. 3 of the 4 patients had previous clinical evidence of HIV encephalopathy. AIDS-related opportunist infection of the central nervous system was excluded. This acute meningo-encephalitic illness probably results from an increase in HIV replication following dose reduction.

AIDS-Related Complex↗