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Biomedical subjects

D Easter

Publications and source records attributed to D Easter.

9 recordsLinked to original sources

A seminested RT-PCR assay for HER2/neu: initial validation of a new method for the detection of disseminated breast cancer cells.

BACKGROUND: Initial validation of a seminested reverse transcription-polymerase chain reaction (RT-PCR) assay for HER2/neu for use in detecting circulating tumor cells in the peripheral blood or bone marrow of breast cancer patients is described. RT-PCR assays for other epithelial markers, including the cytokeratins and carcinoembryonic antigen frequently lack specificity, sensitivity, or both. Thus, there is a need for an assay that is both sensitive and specific to be used to monitor breast cancer patients for micrometastatic or minimal residual disease. METHOD AND RESULTS: Assay conditions were optimized using the MCF7 breast cancer cell line and the Raji B-cell lymphoma cell line. The assay can detect as little as 3 mg of MCF7 RNA within a background of 3 mg of Raji RNA. The assay was positive in 12 of 12 breast tumors. None of the 33 peripheral blood or stem cell samples form patients without evidence of breast cancer were positive. Peripheral blood from 17 breast cancer patients was collected immediately before surgery and evaluated. The assay was positive in five of six patients with Stage II, four of eight patients with Stage I and one of three patients with Stage 0 disease. CONCLUSIONS: The seminested HER2/neu RT-PCR assay compares favorably with RT-PCR assays for other epithelial cell markers in terms of both sensitivity and specificity as a method to detect disseminated breast cancer cells. In breast cancer patients, the higher the disease stage, the more frequently was the assay positive.

Breast Neoplasms↗

Weight gain with valproate or carbamazepine--a reappraisal.

The use of valproate has traditionally been held to be associated with a greater incidence of weight gain than that of other anticonvulsants. This paper presents an analysis of body weight data gathered during a randomized trial comparing valproate with carbamazepine in 260 children aged 4-15 years with newly-diagnosed epilepsy. There were more reports of weight gain as an adverse event in the valproate group than in the carbamazepine group (22 reports in 14 patients vs. nine reports in five patients). However, amongst the 211 patients (103 on valproate and 108 on carbamazepine) in whom objective weight measurements were taken during treatment, there were no differences between the treatments in percentage weight gain from baseline or incidence of excessive weight velocity. Eight patients reporting weight gain on valproate were switched to carbamazepine because of poor seizure control and/or adverse events including weight gain, but three of the four patients for whom body weight measurements were available continued to gain weight on carbamazepine. It is concluded that weight gain may be erroneously attributed to valproate treatment.

Adolescent↗

Percutaneous radiologic drainage of pancreatic abscesses.

OBJECTIVE: The purpose of our study was to review and report the patient selection, techniques, and results of percutaneous drainage of pancreatic abscesses by retrospective review. MATERIALS AND METHODS: Fifty-nine patients (46 men and 13 women) with a mean age of 44 years old had 80 pancreatic abscesses that were drained percutaneously under radiologic guidance (CT, n = 77; sonography, n = 2; and fluoroscopy, n = 1). Abscesses had a wide spectrum of causes, with alcoholic pancreatitis being most common, trauma second most common, and gallstones third. Ten patients had undergone surgery for pancreatic necrosis or abscess. Patients with pancreatic pseudocysts, necrosis, or acute fluid collections were excluded from this study. RESULTS: Of the 59 patients, 51 (86%) were cured with percutaneous drainage and antibiotic therapy. Of the patients who were not cured with percutaneous drainage, seven required surgery and one underwent repeat percutaneous drainage. In the 59 patients, complications included non-life-threatening bleeding in three patients. Ten of 59 patients (17%) had fistulas that spontaneously formed into the gastrointestinal tract. The duration of catheterization ranged from 4 to 119 days, with a mean duration of 33 days. The rate of mortality at 30 days after completion of percutaneous drainage was 8% (5 of 59). CONCLUSION: Percutaneous drainage was an effective therapy for this defined group of patients with pancreatic abscesses. Factors leading to the relatively high success rate described in this study likely included selection of patients; catheters of adequate size, number, and location; careful follow-up with appropriate catheter manipulations; and an integrated, cooperative approach whereby surgeons were willing to permit drainage to effect its benefits, rather than operating prematurely.

Abscess↗

Epilim chrono: a multidose, crossover comparison of two formulations of valproate in healthy volunteers.

The pharmacokinetic properties and relative bioequivalence of two formulations of the antiepileptic Epilim were compared in a three-period, repeat dose, randomized crossover study in 18 male volunteers. A daily dose of 1000 mg of antiepileptic was given either as twice-daily enteric-coated sodium valproate tablets or as twice- or once-daily controlled release tablets (Epilim Chrono, sodium valproate/valproic acid mixture). All regimens were bioequivalent with respect to area under the curve and elimination half-life. The twice-daily controlled release formulation showed reduced mean peak plasma valproate levels and raised mean trough levels compared with the enteric coated tablets. The once-daily controlled release regimen gave reduced mean peak levels but similar mean trough levels to the twice-daily enteric-coated regimen. No major differences between regimens were observed in the time at which peak concentration was observed. Both formulations were well tolerated. The most frequently reported adverse event was mild diarrhoea (all on Chrono treatment) which is probably related to the lack of enteric coating on this formulation. The reduced mean peak-trough variation in plasma valproate levels observed with the twice-daily controlled release regimen is likely to reduce further the low incidence of concentration-related side-effects with sodium valproate and permit more reliable plasma level monitoring. This study also indicates that once-daily treatment with Epilim controlled release would be a suitable replacement for twice-daily dosing with either formulation. Once-daily treatment is likely to give considerable benefits both in convenience and in better patient compliance.

Adolescent↗

Isolation of an immunosuppressive trauma peptide and its relationship to fibronectin.

The purpose of this study was to characterize a suppressive active glycopeptide (SAP) using affinity chromatography (AFFI) and explore its similarity to fibronectin (FN) degradation products. It is postulated that SAP is a degradation fragment of a large serum-borne protein, possibly FN. Human trauma serum (HTS) and elastase-degraded human FN were run over an AFFI prepared with monoclonal antibody to SAP. Bound protein was eluted with 2M NaCl and dialyzed to remove salt. Immunosuppressive activity of HTS and FN eluates was monitored using inhibition of neutrophil chemotaxis (CTX). Active fractions were compared to the starting material and controls with 15% PAGE. AFFI eluates of HTS revealed a high molecular weight protein band (450 kd) with no inhibitory CTX activity and singular low molecular weight protein (LMW) band (less than 20,000) with 93% +/- 5% CTX suppression. Elastase-digested purified human FN eluates run under identical conditions over the same AFFI revealed two bands with an identical elution profile as HTS eluates. CTX suppression 95 +/- 5% was seen only with the LMW band. Incubation of enriched LWF fragments of digested FN and HTS with whole FN reversed CTX suppression. This suggests affinity purification of a single LMW suppressive glycopeptide which may bind to or be a degradation product of plasma or cellular fibronectin.

Chemotaxis, Leukocyte↗