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Biomedical subjects

P Hewitt

Publications and source records attributed to P Hewitt.

At least 19 recordsLinked to original sources
PubMed2004

Phase I and II enzyme characterization of two sources of HepG2 cell lines.

1: The metabolism by HepG2 cell from two sources (M1, M2) of 12 substrates is reported: ethoxyresorufin, ethoxycoumarin, testosterone, tolbutamide, chlorzoxazone, dextromethorphan, phenacetin, midazolam, acetaminophen, hydroxycoumarin, p-nitrophenol and 1-chloro-2,4-dinitrobenzene (CDNB), and a pharmaceutical compound, EMD68843. 2: Activities varied markedly. Some were present in M1 (CYP1A, CYP2C9, CYP2E1) but absent in M2. M1 had a more complete set of Phase I enzymes than M2. CYP1A2, CYP2C9, CYP2D6, CYP2E1 and CYP3A activities were present at levels similar to human hepatocytes. Phase II metabolism differed between M1 and M2. M1 conjugated hydroxycoumarin and p-nitrophenol to glucuronides only, whereas M2 produced sulfates. Glutathione conjugation of CDNB metabolism was 10-fold higher in M1 than in M2, but was still much lower than in human hepatocytes. CYP2E, CYP2C, CYP2B6 and CYP3A (but not CYP1A, glucuronyl S-transferase or S-transferase) were inducible in M1. Metabolites of EMD68843, produced by induced (but not uninduced) M1 were the same as those produced in human hepatocytes. 3: In conclusion, HepG2 cells have both Phase I and II enzymes, which activities and at what levels depend on the source and culture conditions. Therefore, HepG2 cells routinely used in in vitro assays should be characterized for their drug-metabolizing capabilities before any results can be fully interpreted.

Aryl Hydrocarbon Hydroxylases↗
PubMed2003

Paclitaxel for anthracycline-resistant AIDS-related Kaposi's sarcoma: clinical and angiogenic correlations.

BACKGROUND: Murine data indicate that angiogenesis is central to the aetiopathogenesis of Kaposi's sarcoma (KS). Therefore, we measured angiogenic cytokines and growth factors in patients with AIDS-related KS during treatment with both antiretrovirals and second-line paclitaxel chemotherapy. Cytokines measured included tumour necrosis factor-alpha (TNF-alpha), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and the interleukins IL-2, -6 and -12. PATIENTS AND METHODS: Enzyme-linked immunosorbent assays (ELISAs) were carried out to measure plasma cytokine levels in 17 patients with AIDS-related KS who had progressed within 6 months of receiving liposomal anthracyclines and were treated with paclitaxel 100 mg/m(2) every 2 weeks. Measurements were carried out before progression, at commencement and at the completion of paclitaxel. RESULTS: The objective response rate to paclitaxel was 71% (95% confidence interval 60% to 81%). In 17 patients with AIDS-related KS, we observed eight partial responses and four complete responses. Patients with AIDS Clinical Trial Group stage T1 disease had higher plasma VEGF (P = 0.05) and lower plasma TNF-alpha levels (P = 0.05) than patients with earlier stage T0 KS. There were no correlations between plasma cytokines (bFGF, VEGF, TNF-alpha, and IL-2,-6 and -12) and the CD4 and CD8 cell counts or HIV-1 RNA viral load. Response to paclitaxel was associated with a fall in plasma IL-6 levels (P = 0.04) but no change in other cytokines. There were no significant changes in CD4, CD8, CD16/56, CD19 cell counts and HIV-1 viral loads during chemotherapy. CONCLUSIONS: Angiogenic cytokines may correlate with KS disease extent but not with cellular immune function or HIV viraemia. Response to paclitaxel therapy correlates with a fall in plasma IL-6 levels and recent data indicate this may be a surrogate marker of KS-associated herpesvirus viral load. Overall, clinical response in KS correlates poorly with known angiogenic cytokines.

Acquired Immunodeficiency Syndrome↗
PubMed2002

The contribution of transfusion to HCV infection in England.

The English HCV lookback programme has identified some individuals with transfusion-transmitted HCV infection. The path from the collection of donations from HCV-infected donors to the identification of infected recipients was constructed. The probability of different outcomes at each branch was derived from data collected during this programme. This path of probabilities was then used to produce a complete estimate of the number of recipients infected by blood transfusions (dead and alive at the end of 1995) by re-entry of blood components that fell out of the lookback at various steps prior to recipient testing, and entry of components from HCV-infected donations that were never identified for lookback. Less than 14,000 recipients were estimated to have been infected with HCV during the decade prior to the start of donation testing. Over 60% of these were expected to have died by the end of 1995. Transfusion has infected a large group of individuals. However, this group constitutes a very small, and declining, proportion of all HCV infections in the population.

Blood Transfusion↗
PubMed2000

Prospective investigation of transfusion transmitted infection in recipients of over 20 000 units of blood. TTI Study Group.

OBJECTIVES: To follow up recipients of 20 000 units of blood to identify any transmissions of infections through blood transfusion. DESIGN: Follow up study of recipients of transfusion. SETTING: 22 hospitals in north London. PARTICIPANT: Adult patients who had recently been transfused. MAIN OUTCOME MEASURES: Patients had further blood samples taken at 9 months that were tested for markers of hepatitis B and C and HIV and human T cell leukaemia/lymphoma virus type I or II (HTLV) infections. Recent infections were distinguished from pre-existing infections by comparison with blood samples taken before transfusion. RESULTS: 9220 patients were recruited, and 5579 recipients of 21 923 units of blood were followed up. No transfusion transmitted infections were identified. The incidence of transfusion transmitted infections was 0 in 21 043 units (95% confidence interval for risk 0 to 1 in 5706 recipients) for hepatitis B; 0 in 21 800 units (0 to 1 in 5911 recipients) for hepatitis C; 0 in 21 923 units (0 to 1 in 5944 recipients) for HIV; and 0 in 21 902 units (0 to 1 in 5939 recipients) for human T cell leukaemia/lymphoma virus. Three patients acquired hepatitis B during or after hospital admission but not through transfusion; 176 (3%) had pre-existing hepatitis B infection. Sixteen (0.29%) patients had hepatitis C, and five (0.09%) had human T cell leukaemia/lymphoma virus. CONCLUSIONS: The current risk of transfusion transmitted infections in the United Kingdom is very small, though hospital acquired infections may arise from sources other than transfusion. A considerable proportion of patients have pre-existing infections.

Adolescent↗
PubMed2000

Effects of handling and storage of blood on the stability of hepatitis C virus RNA: implications for NAT testing in transfusion practice.

BACKGROUND AND OBJECTIVES: To determine the stability of hepatitis C virus (HCV) RNA during transport and storage of blood samples from donors, prior to screening for HCV by nucleic acid amplification technology. MATERIALS AND METHODS: Various blood and plasma sample types were stored for up to 120 h at different temperatures and the HCV RNA level was measured using an in house quantitative reverse transcription-polymerase chain reaction. RESULTS: No decline in HCV RNA level was observed after 72 h of storage of whole blood at 4 degrees C in EDTA tubes (Greiner) and Plasma Preparation Tubes (PPT; Becton Dickinson), while insignificant declines of 0.2 log10 and 0. 25 log10 occurred at 25 degrees C after 72 h in the EDTA tubes and PPT tubes, respectively. When whole blood was stored with mixed anticoagulants CPDA-1 and EDTA for up to 120 h, no decline in HCV RNA level was observed at 4 degrees C and 25 degrees C, while a significant decline of 0.37 log10 occurred at 37 degrees C after 120 h. The temperature during transportation was investigated with a 12-hour period at 25 degrees C and 37 degrees C before storage at 4 degrees C for 108 h. Neither temperature resulted in any loss of HCV RNA in comparison with 120 h of storage at 4 degrees C. CONCLUSION: Whole blood anticoagulated with EDTA or CPDA-1/EDTA may be stored at up to 25 degrees C (room temperature) for up to 5 days without any significant loss in plasma HCV RNA level.

Adenine↗
PubMed1999

Hepatitis C lookback programme: a single hospital experience.

As part of the national Hepatitis C (HCV) Lookback Programme, HCV-infected donors donating blood after September 1991 were identified and the fate of their previous donations received at a single hospital were traced; 123 of 160 implicated blood components were traceable and transfused. Only 19 recipients were alive and traceable and were tested for HCV. Nine of the 14 recipients (64%) of HCV-positive donations and 2 of 5 recipients (40%) of HCV-indeterminate donations had evidence of HCV infection. Neither the number of donor exposures nor the type of component was predictive of recipient HCV status. Three recipients have chronic active hepatitis. The Hepatitis C Lookback Programme successfully identifies some but not all cases of transfusion-transmitted HCV. Transfusion records, particularly in the medical case notes, should be substantially improved. Many of the traced recipients are young, so that identification of HCV is of great importance.

Adolescent↗
PubMed1999

Large-scale HCV RNA screening in first-time blood donors: the first step towards genomic screening of blood donations. HCV RNA Screening Study Group.

BACKGROUND AND OBJECTIVES: Individual genomic screening for viruses in blood donations is becoming increasingly pressing as an alternative to pool testing to improve the safety of the blood supply. MATERIALS AND METHODS: To determine the feasibility and, possibly, efficacy of genomic screening for hepatitis C virus (HCV) in the blood service setting, a representative population of first-time blood donors was screened individually with a semi-automated genomic amplification assay for HCV RNA. First-time blood donors in two blood centres in the United Kingdom were screened in parallel for anti-HCV and HCV RNA by RT-PCR. RESULTS: 8, 417 serum samples were screened. A 99.95% specificity was observed and one anti-HCV-positive, HCV-RNA-positive donation was found. No seronegative HCV-RNA-positive donations were detected. CONCLUSIONS: These results are consistent with the low prevalence of HCV infection in blood donors from the London area and demonstrate the high level of performance of the individual genomic screening method used in this study. When fully automated, such a method would be a highly suitable candidate for routine, automated genomic screening of HCV and, subsequently, of other pathogenic blood-borne viruses.

Autoanalysis↗
PubMed1997

Laparoscopic colectomy.

BACKGROUND: Laparoscopic colectomy has developed with the explosion of technology that has followed laparoscopic cholecystectomy. Accumulation of skills in general laparoscopic surgery has made complex surgery, such as colectomy, feasible. METHODS: Three hundred fifty-nine laparoscopic cases were prospectively studied. Data has been kept on benign and malignant cases, operative results, hospital stay, and morbidity. Special care has been taken to follow malignant cases, looking for recurrence of disease. RESULTS: There were 359 cases (206 females, 153 male) average age 58.8 years (18-94), and 149 patients had malignancy. All types of resections were performed, including 151 anterior resections, 66 right hemicolectomies (RHC), 36 total colectomies, and 22 rectopexies. Operating times fell with experience-the last 20 cases of anterior resection took 150 min (110-240) and of RHC took 130 min (65-210). Twenty-six (7%) cases were converted to open surgery. Hospital stays for anterior resection lasted 5-7 days (2-33); in the last 20 cases the average stay was 4 days. Morbidity included seven leaks (2.7%), four strictures (1.2%), 12 wound infections (3.3%), and nine ileus (2.5%). There were six deaths within 30 days-sepsis, myocardial infarction, aspiration pneumonia, and disseminated liver metastases. One hundred forty-nine cancer cases have had ten recurrences: one pelvic recurrence, six liver metastases, two para-aortic nodal, and one case of disseminated disease. Average time of recurrence was 33 months (15-46 months). CONCLUSIONS: Laparoscopy in the hands of experienced laparoscopic surgeons is a safe, efficient procedure. All types of procedures are possible. Early results in 149 malignancies are encouraging and recurrence rates are low. Prospective studies, now that skills are developed to a level comparable to that of open surgery, are now being performed to further assess laparoscopy's possible role in treating cancer.

Adolescent↗
PubMed1997

Chronic anemia due to parvovirus B19 infection in a bone marrow transplant patient after platelet transfusion.

BACKGROUND: Many reports document the transmission of human parvovirus B19 (B19) infection by clotting factor concentrates manufactured from large plasma pools. Transmission via other blood components originating from a single donor or a small number of donors, however, seems to occur only rarely. The study reported here identifies a B19 infection that was transmitted via a platelet donation. CASE REPORT: A multiply transfused allogeneic bone marrow transplant patient developed chronic anemia due to persistent B19 infection. The anemia responded to therapy with intravenous immunoglobulin. It was postulated that a transfusion was the source of the B19 infection. Archived sera from 90 implicated blood donors were tested for B19 IgM and DNA by the use of dot-blot hybridization and a nested polymerase chain reaction with primers from the B19 nonstructural gene. B19 DNA from patient and donor sera were sequenced. One of the 90 blood donors (Donor A) was B19 IgM positive and had a high level of B19 DNA. The patient was viremic 3 days after transfusion of platelets from this donor, and the sequence of B19 DNA from the patient exactly matched that of B19 DNA from the donor. A second blood donor (Donor B) had a low level of B19 DNA but was IgM negative. The patient showed no evidence of B19 infection after the transfusion of red cells from Donor B, and the sequence of this donor's B19 DNA was different from that in the patient. CONCLUSION: Blood Donor A with asymptomatic acute B19 infection was the source of B19 infection in the bone marrow transplant patient. Donor B with a low level of B19 DNA was not the source of infection.

Adult↗