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Biomedical subjects

H Warren

Publications and source records attributed to H Warren.

15 recordsLinked to original sources

Angiocentric recruitment of lymphocytes into the lung after the intrabronchial instillation of antigen.

The pathogenesis of acute lymphocytic inflammation in the lower respiratory tract appears to involve the recruitment of lymphocytes out of the blood stream and into the extravascular lung tissue. To investigate the membrane molecules regulating this process, we used the intrabronchial instillation of cellular antigen to trigger lymphocyte recruitment into the lower respiratory tract. Sheep presensitized 6 to 10 weeks earlier at a remote site were intrabronchially challenged with 1-5 x 10(7) cells from a B lymphoblastoid cell line. The cells were instilled into a subsegmental bronchus through a bronchial catheter. The stimulated and contralateral control segments were studied at a peak of inflammation, approximately 72 hours after antigen stimulation. Gross and microscopic studies of the stimulated segment demonstrated localized inflammation characterized by the perivascular infiltration of lymphocytes. In contrast, control areas of the lung demonstrated only scattered perivascular lymphocytes. Immunohistochemistry of the stimulated lung showed that the majority of these perivascular cells were CD3+ CD4+ lymphocytes. The T lymphocytes expressed high levels of the cell adhesion molecules beta 1 integrin and LFA-1, but low levels of the L-selectin membrane molecule. Immunohistochemistry of the endothelial cells associated with the lymphocyte infiltrates demonstrated intense staining of the ICAM-1, and beta 1 integrin adhesion molecules. Electron microscopic studies of the endothelial cells in the antigen stimulated areas of the lung confirmed morphologic changes consistent with endothelialitis. These results suggest that the intrabronchial instillation of cellular antigen stimulates an angiocentric T-cell infiltration regulated by activated pulmonary endothelial cells. The histologic and morphologic findings are remarkably similar to those observed during acute lung transplant rejection.

Animals↗

Immunoglobulin G-mediated inflammatory responses develop normally in complement-deficient mice.

The role of complement in immunoglobulin G-triggered inflammation was studied in mice genetically deficient in complement components C3 and C4. Using the reverse passive Arthus reaction and experimental models of immune hemolytic anemia and immune thrombocytopenia, we show that these mice have types II and III inflammatory responses that are indistinguishable from those of wild-type animals. Complement-deficient and wild-type animals exhibit comparable levels of erythrophagocytosis and platelet clearance in response to cytotoxic anti-red blood cell and antiplatelet antibodies. Furthermore, in the reverse passive Arthus reaction, soluble immune complexes induce equivalent levels of hemmorhage, edema, and neutrophillic infiltration in complement-deficient and wild-type animals. In contrast, mice that are genetically deficient in the expression of Fc receptors exhibit grossly diminished reactions by both cytotoxic antibodies and soluble immune complexes. These studies provide strong evidence that the activation of cell-based Fc gamma R receptors, but not complement, are required for antibody-triggered murine inflammatory responses.

Anemia, Hemolytic↗

Response to regional chemotherapy in patients with variant hepatic arterial anatomy.

Regional chemotherapy for colorectal liver metastases is conventionally delivered by a catheter inserted into the gastroduodenal artery. However, up to 40 per cent of patients have 'unconventional' hepatic arterial anatomy. The response rate to regional chemotherapy was examined in 28 patients with normal and in 17 with variant hepatic arterial anatomy. There was no significant difference in response rates between the two groups.

Antimetabolites, Antineoplastic↗

Measured scattered x-ray energy spectra for simulated irradiation geometries in diagnostic radiology.

In this study, scattered x-ray distributions were produced by irradiating an anthropomorphic pelvis phantom under fluoroscopic conditions using incident beams generated at tube potentials between 61 kVp and 112 kVp. Both overcouch and undercouch x-ray tube orientations were used when irradiating the phantom. The energy spectrum of the scattered x rays was measured with a germanium x-ray detector. Two measurement geometries were employed: (i) the detector placed at 90 degrees to the incident x-ray beam to determine the energy spectra incident on the trunk region of staff and (ii) the detector placed at 45 degrees to the x-ray beam, measuring spectra incident on the head and neck region. The effect of irradiation area on the scattered spectra was also investigated. Spectral distributions, along with mean energy and half-value layer (HVL) in mm Al, are presented for each spectrum. Energy spectra measured at 90 degrees to the incident x-ray beam were found to have HVLs approximately 10%-15% greater than the corresponding primary incident spectrum, for both overcouch and undercouch irradiations. The magnitude of the irradiation area had negligible effect on the mean energy and HVL of the spectra.

Biophysical Phenomena↗

Dynamic hepatic scintigraphy in colorectal cancer.

The clinical usefulness of the hepatic perfusion index (HPI) at the time of presentation has been evaluated in patients with colorectal cancer. In 83 consecutive patients, the HPI was abnormally elevated in 34 of 37 (93%) patients with overt metastases. This study confirms that the HPI is elevated in most patients with overt hepatic metastases. Long-term follow-up of patients with abnormal HPI and no obvious liver metastases is continuing.

Carcinoma↗

Pharmacokinetic study of 5-fluorouracil in a novel dialysate solution: a long-term intraperitoneal treatment approach for advanced colorectal carcinoma.

Five patients with advanced colorectal and gastric carcinoma with peritoneal deposits were treated by continuous weekdays intraperitoneal (i.p.) instillation of 5-fluorouracil (5-FU) 200 mg m-2 day-1 in a novel dialysate solution that ensures maximal exposure of peritoneal areas liable to bear tumours for 24 h. A solution of icodextrin, a glucose polymer, in a 21 twin-bag delivery system allowed a single daily exchange and demonstrated the feasibility of long-term continuous ambulatory treatment with up to 17.4 g of 5-FU, delivered intraperitoneally, in this initial study. During the entire study, there were 235 fluid exchanges or 470 connections and disconnections and no bacterial peritonitis or exit site infection were observed. There was no treatment-associated toxicity worse than WHO grade 2. Drug concentrations in both peritoneal and plasma compartments followed a first-order model with similar half-life value of 1.3 h. 5-FU pharmacokinetic parameters (half-life values, total body clearance, peritoneal clearance and pharmacological advantage of the i.p. route) with this novel icodextrin carrier solution were similar to those obtained in other referenced pharmacokinetic studies with other carrier solutions (dextrose dialysate and lactated Ringer's solutions). This confirms that icodextrin solution is physiologically neutral, drug compatible and allows adequate dwell times with constant fluid balance for long-term continuous intraperitoneal chemotherapy. The pharmacokinetic parameters from this study will be used to design a loading dose infusion schedule in an attempt to maintain steady-state i.p. 5-FU levels in a new multicentre phase I trial.

Colorectal Neoplasms↗

Hepatic arterial haemodynamics changes following intra-arterial angiotensin II infusion: duplex/colour Doppler sonography.

Previous studies have shown that the delivery of cytotoxic microspheres to liver tumours may be improved by manipulating the tumour to normal liver blood flow ratio using angiotensin II (AT-II). The optimization of this targeting requires the assessment of the temporal blood flow changes induced by agents such as AT-II. Duplex/colour Doppler sonography (DCDS) was evaluated as a means of studying the effects of AT-II infusion on hepatic arterial blood flow (HABF) and arterial resistance in patients with colorectal liver metastases. HABF was measured continuously in six patients with colorectal liver metastases using DCDS before, during and after an infusion of AT-II (15 micrograms in 3 ml of saline over 90 s) via a hepatic artery catheter. The baseline level of HABF was 320 +/- 87 ml/min (mean +/- S.D.), and this was reduced by 70-76% within 30 s of the start of AT-II infusion. HABF recovered rapidly from the end of the infusion, and increased by up to 20% above the baseline for approximately 2 min. Arterial resistance showed reciprocal changes in all cases. These changes were both quantitatively and qualitatively similar to intra-operative measurements previously performed in the same patients using a standard intra-operative flowmeter. The degree of concordance obtained from the intra- and post-operative measurements confirms the effectiveness of DCDS in assessing the temporal changes in hepatic arterial blood flow caused by AT-II. Prior to the start of therapy, the evaluation of vasoconstrictor agents should be carried out in individual patients to predict response, in order to establish the optimal phase for the injection of cytotoxic microspheres.

Aged↗

Infrainguinal bypass surgery: factors determining late graft patency.

The results of 373 infrainguinal bypass grafts, in a single centre, between 1980 and 1988 are reviewed. One hundred and thirty in situ vein (ISV), 47 reversed saphenous vein (RSV), 118 polytetrafluoroethylene (PTFE) and 78 human umbilical vein (HUV) grafts were used. The indications for surgery were disabling claudication in 25 per cent of patients and limb salvage in 75 per cent. In 36 per cent of operations the distal anastomosis was above the knee and in 64 per cent it was below the knee. Overall 5-year patency rates and limb salvage rates respectively were, for ISV (41 and 69 per cent), RSV (62 and 90 per cent), PTFE (31 and 67 per cent) and HUV (29 and 59 per cent). There was no significant difference in patency among these grafts at the above-knee level, but significant differences between vein and prosthetic grafts were evident below the knee (P less than 0.001). Using a proportional hazards model the three factors that consistently correlated with late graft patency were graft type (P less than 0.001), site of distal anastomosis (P less than 0.001) and distal run-off (P less than 0.001). Overall, the results suggest that prosthetic grafts are a suitable alternative to autogenous vein when the distal anastomosis is above the knee, but vein should always be used, if available, below the knee joint.

Adult↗

The radiation dose to accompanying nurses, relatives and other patients in a nuclear medicine department waiting room.

The radiation dose to accompanying nurses, relatives and other patients in a nuclear medicine department waiting room was assessed at 5 min intervals by observing the seating arrangement. The total radiation dose to each person was calculated, using fixed values of dose rate per 100 MBq activity for radionuclides, and applying the inverse square law. Radioactive decay and attenuation effects due to intervening persons were also taken into account. The median radiation doses to accompanying nurses, relatives and other patients were 2.3, 2.0 and 0.2 microSv with maximum values of 17, 33 and 5 microSv respectively. In all cases, the radiation dose received by patients was less than 0.2% of the radiation dose resulting from their own investigation. Also, the maximum radiation dose received by an accompanying nurse or friend was less than 1% of their appropriate annual dose limit. Similar values were obtained with calculations based on a 15 min time interval. The radiation doses received by those in a nuclear medicine department waiting room are small, and separate waiting room facilities for radioactive patients are unnecessary.

Family↗

Changes in peritoneal dialysis nursing.

Improvements in technology have assisted nurses with the care of peritoneal dialysis patients. This article will discuss changes in the methods of accessing the peritoneal cavity and other changes that have allowed peritoneal dialysis to become an effective treatment modality for chronic as well as acute renal failure. These changes include the development of cyclers, plastic solution bags, and devices to facilitate bag exchanges and decrease the incidence of peritonitis.

History, 20th Century↗

Slips of the tongue in very young children.

This paper investigates the difference in the frequency with which adults and young children make slips of the tongue. The slips analyzed were taken from two corpora of speech. The first consists of the speech of one child in interaction with her mother; the second corpus consists of the speech of eight children in interaction with their teacher. The results suggest that young children make significantly fewer slips than do adults. This finding is consistent with a psychoanalytic understanding of slips--i.e., that young children should make fewer slips because they are less inclined to suppress and repress ideas and impulses.

Child Language↗