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Biomedical subjects

P Harrison

Publications and source records attributed to P Harrison.

At least 127 records · Page 7Linked to original sources

Hepatic expression of hepatocyte-growth-factor-like/macrophage-stimulating protein mRNA in fulminant hepatic failure.

We investigated whether impaired Kupffer cell phagocytosis in fulminant hepatic failure could be due to reduced synthesis of hepatocyte-growth-factor-like/macrophage-stimulating protein (HGFL/MSP), a serum protein synthesised predominantly in hepatocytes and required by tissue macrophages for phagocytosis. Hepatic expression of the 3.0 kb HGFL/MSP mRNA, assessed by northern hybridisation, was lower in nine patients with fulminant hepatic failure undergoing liver transplantation than in three liver grafts as controls (median absorbance units 97 [range 15-1200] versus 1114 [1100-1120], respectively; p < 0.05). Decreased hepatic HGFL/MSP production might cause impaired Kupffer cell phagocytosis in fulminant hepatic failure.

Adult↗

Repeated cleaning of protein A affinity column with sodium hydroxide.

Protein A attached to an affinity adsorbent was shown to be remarkably resistant to 0.5 M NaOH. Even repeated treatments gave only a small decrease in functional capacity and no adverse effect on leakage of the protein A into the eluate. This simple cleaning procedure should be useful in applications where antibodies need to be purified free from the risk of contamination with endotoxins or micro-organisms, e.g., for in vivo therapy, either in clinical trials or experimental animals. It can also prevent cross-contamination when the same protein A adsorbent is used for different batches of antibody.

Adsorption↗

1 alpha,25-Dihydroxyvitamin D3 promotes monocytopoiesis and suppresses granulocytopoiesis in cultures of normal human myeloid blast cells.

Primitive myeloid blast cells (2-10 x 10(6)) were purified from 18-22-week fetal liver-derived mononuclear cell preparations by negative selection followed by counterflow cell elutriation. The cells, when maintained in liquid culture in the presence of 100 U/ml interleukin-3 (IL-3) for the first 5 days and 10 U/ml IL-3 and 30 ng/ml granulocyte colony-stimulating factor thereafter, underwent considerable proliferation resulting in an approximately 30-fold increase in cell number by day 14. Analyses of cell morphology and of the numbers of cells that expressed the neutrophil-associated antigen CD15, the monocyte-associated antigen 61D3, and enzymes alpha-naphthyl acetate esterase (ANAE), human leukocyte elastase, and cathepsin G revealed that proliferation of the cells was associated with their concomitant differentiation toward neutrophils and monocytes. The cultures generated predominantly neutrophils; by day 14, wells seeded with 2 x 10(5) cells produced approximately 5 x 10(6) neutrophils as opposed to only approximately 3.5 x 10(5) cells with a monocytoid morphology. This predominance of granulocytopoiesis over monocytopoiesis was confirmed by the numbers of cells that had acquired expression of the CD15 antigen and ANAE, which were approximately 2 x 10(6) and 1 x 10(5), respectively. By contrast, parallel cultures containing 100 nM 1 alpha,25-dihydroxyvitamin D3 (VitD3) generated more monocytes than neutrophils. At day 14, VitD3-treated cultures contained approximately 2 x 10(6) cells with morphologies consistent with their differentiation toward monocytes and approximately 1 x 10(6) ANAE-positive cells, compared with approximately 9.5 x 10(5) cells having morphologies of granulocyte-series cells and approximately 4.5 x 10(4) CD15-positive cells. In both control and VitD3-treated cultures, the enzymes cathepsin G and human leukocyte elastase were expressed almost exclusively by cells that were differentiating toward neutrophils. These data reveal that VitD3 promotes monocytopoiesis and suppresses granulocytopoiesis of primitive blast cells.

Calcitriol↗

Postoperative epidural bupivacaine-morphine therapy. Experience with 4,227 surgical cancer patients.

BACKGROUND: We prospectively studied surgical cancer patients who received epidural bupivacaine-morphine to determine perioperative morphine use, side effects, and complications. METHODS: All study patients received general-epidural anesthesia followed by epidural analgesia with 0.05% or 0.1% bupivacaine and 0.01% morphine at a rate of 5-10 ml.h-1 to keep the dynamic pain score at less than 5 (of 10). Patients were evaluated daily for pain relief, side effects, catheter migration, accidental removal, hypotension, respiratory rate, mental status changes, nausea and vomiting, and pruritus. RESULTS: Over 4 yr, 4,227 patients (61% women, aged 68 +/- 24 yr) were studied. Lumbar epidural catheters (n = 2,248 or 53.18%) were used more frequently than thoracic catheters (n = 1,979 or 46.82%) (P < 0.00001). Most of the patients were discharged to the surgical wards after the procedures (n = 3,001, 71%). Those patients (n = 1,226, 29%) admitted to the surgical intensive care unit, spent 1.2 +/- 0.8 days. Epidural catheter failure occurred in 283 (6.3%) patients. Length of epidural analgesia therapy was 6.3 +/- 2.6 days. There were three cases (0.07%) of respiratory depression which were treated with oxygen, intravenous naloxone, and by stopping the epidural infusion for 6 h. Hypotension occurred in 126 patients (3%). There were no apparent cases of catheter migration to either the subdural or subarachnoid space. Nausea or vomiting occurred in 929 patients (22%). Pruritus occurred in 930 patients (22%). CONCLUSIONS: Continuous epidural analgesia with 0.05-0.1% bupivacaine and 0.01% morphine is an effective method of postoperative analgesia with a low incidence of side effects, that can be safely administered on the surgical wards with no special monitoring equipment.

Adult↗

Successful use of all-trans retinoic acid in acute promyelocytic leukaemia presenting during the second trimester of pregnancy.

The development of acute leukaemia in pregnancy is a rare event, with an estimated incidence of 0.9-1.2 cases per 100,000 per year and with the majority of cases occurring in the second and third trimesters. We report a case of acute promyelocytic leukaemia (APL) developing during the second trimester of pregnancy which was successfully treated with all-trans retinoic acid (ATRA) resulting in a complete morphological remission.

Adult↗

Non-transferrin bound iron and neutropenia after cytotoxic chemotherapy.

AIMS: To investigate and characterise the appearance of non-transferrin bound iron (NTBI) in the serum of patients after cytotoxic chemotherapy and to compare this with the onset and duration of neutropenia. METHOD: Non-transferrin bound iron was measured by a bleomycin assay in patients undergoing intensive chemotherapy for treatment of acute leukaemia or lymphoma. RESULTS: NTBI was detected after 26 of 27 courses of chemotherapy and lasted for a mean of 14.5 days. The presence of NTBI correlated with the serum iron binding saturation, but not with serum ferritin. Neutropenia occurred after all courses of chemotherapy and lasted for a mean of 20.0 days. NTBI and neutropenia occurred concurrently after 23 courses of chemotherapy, and had a mean joint duration of 9.5 days. CONCLUSIONS: NTBI is consistently present in the serum of patients after cytotoxic chemotherapy, often at the same time as the patient is neutropenic. This may be an additional risk factor for the development of infective episodes after chemotherapy.

Acute Disease↗