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Biomedical subjects

R E Lee

Publications and source records attributed to R E Lee.

At least 19 recordsLinked to original sources
PubMed1992

Cooling rate influences cryoprotectant distribution and organ dehydration in freezing wood frogs.

Ice formation in the freeze-tolerant wood frog (Rana sylvatica) induces the production and distribution of the cryoprotectant, glucose. Concomitantly, organs undergo a beneficial dehydration which likely inhibits mechanical injury during freezing. Together, these physiological responses promote freezing survival when frogs are frozen under slow cooling regimes. Rapid cooling, however, is lethal. We tested the hypothesis that the injurious effects of rapid cooling stem from an inadequate distribution of glucose to tissues and an insufficient removal of water from tissues during freezing. Accordingly, we compared glucose and water contents of five organs (liver, heart, skeletal muscle, eye, brain) from wood frogs cooled slowly or rapidly during freezing to -2.5 degrees C. Glucose concentrations in organs from slowly cooled frogs were significantly elevated over unfrozen controls, but no significant increases occurred in rapidly cooled frogs. Organs from slowly cooled frogs contained significantly less water than did those from controls, whereas water contents from rapidly cooled frogs generally were unchanged. Rapid cooling therefore inhibited the production and distribution of cryoprotectant and organ dehydration during freezing. This inhibition may result from an accelerated, premature failure of the cardiovascular system.

Adaptation, Physiological↗
PubMed1992

Lymphoma imaging with a new technetium-99m labelled antibody, LL2.

The lesion detection capability of a new technetium-99m labelled B-cell lymphoma monoclonal antibody (MoAb) imaging agent, LL2, was evaluated in 8 patients with non-Hodgkin's lymphoma and 1 patient with chronic lymphocytic leukaemia. The MoAb kit consists of a 1-vial, 1-mg Fab' form of LL2 ready for instant labelling with technetium. The patients were injected with approximately 925 MBq (25 mCi) of 99mTc-LL2 Fab' (1 mg), and planar and single photon emission tomography (SPET) studies were performed at 3-4 h post injection and at 24 h. There was no evidence of thyroid or stomach activity up to 24 h. Uniform splenic uptake was seen in all patients. Two non-lymphoma patients were also administered with the same agent and demonstrated a similar splenic distribution; therefore, splenic targeting was not scored as tumour-specific. A total of 29 from 48 tumour sites were detected by scintigraphy, including tumours of various grades and histological types. Excluding 1 patient who had a large tumour burden of over 500 g, 29 of 33 lesions were detected. One patient was free of disease at the time of the study and had a negative scan. Another patient showed excellent targeting of gallium-negative sites in the liver and bone. The bone involvement was not known prior to the antibody study and was subsequently confirmed by a bone scan. Additional sites of MoAb localization could not be followed in this group, since most patients went on to radioimmunotherapy immediately following the 99mTc-LL2 study.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1992

Relationship between the flagellates and the ciliates.

The flagellates and the ciliates have long been considered to be closely related because of their unicellular nature and the similarity in the structures of the axoneme of the flagella and cilia in both groups. Most protozoologists believe that the ciliates arose from a flagellate. The flagellates that are most similar in structure to the ciliates are the dinoflagellates and two genera of uncertain taxonomic position, Colponema and Katablepharis. Structurally, dinoflagellates have a number of similarities with ciliates. These include the similarity of the cortical alveoli in the ciliates to the thecal vesicles in the dinoflagellates, the possession of tubular cristae, the similarity of the parasomal sac of the ciliates to the pusule of the dinoflagellates, the possession of similar trichocysts and mucocysts, and some similarity in the feeding apparatus. Colponema spp. are probably related to the dinoflagellates and have many of the same similarities with the ciliates. Katablepharis spp. are very similar in structure to the swarmer (embryo) of the suctorian ciliates. Indeed, reduction in the number of cilia to two in the suctorian swarmer and elimination of the macronucleus would result in a cell that is very similar to the Katablepharis cell. The feeding apparatus of Katablepharis spp. and the rest of the ciliates consists of two concentric microtubular arrays associated with vesicles. Information available from nucleotide sequencing of rRNA places the dinoflagellates in an ancestral position to the ciliates. The rRNA of Colponema and Katablepharis spp. has not yet been investigated. The use of stop codons in mRNA is discussed in relation to phylogeny.

Animals↗
PubMed1992

Results of a survey of doses to paediatric patients undergoing common radiological examinations.

A survey has been performed to investigate typical radiation dose levels for children undergoing a number of common radiological examinations. Doses have been assessed using a Diamentor ionization chamber to measure dose-area product, and by attaching thermoluminescent dosemeters to the patient's skin to determine entrance and organ doses. The survey has been automated by using a personal computer for data collection and storage. Doses have been monitored for a large number of children, primarily in a dedicated paediatric X-ray room, and the results presented can be used as a baseline for making comparative measurements elsewhere. Entrance skin doses were found to range from 0.3 mGy to 5.7 mGy for radiographic examinations, and values of dose-area product from 3 to 225 cGy cm2. The corresponding dose ranges for fluoroscopic examinations are 7.4-26.2 mGy and 130-1241 cGy cm2.

Adolescent↗
PubMed1992

Magnetic resonance angiography of the carotid artery combining two- and three-dimensional acquisitions.

To assess the agreement between magnetic resonance angiography and conventional angiography in the evaluation of carotid stenosis, 61 carotid arteries of 40 patients were studied by combined two- and three-dimensional magnetic resonance angiography and conventional angiography. Stenosis of the internal carotid artery was categorized as mild, moderate, severe, critical, or complete occlusion. In 42 arteries, the degree of stenosis according to magnetic resonance angiography correlated exactly to that found by conventional angiography. In the remaining 19 carotid arteries, the magnetic resonance angiographic measurement of stenosis differed from the conventional angiographic measurement by only one size category. The Spearman rank correlation coefficient was 0.95 (p < 0.001). This study showed that by combining information from two- and three-dimensional magnetic resonance angiographic studies and making use of the advantages of each method, magnetic resonance angiography was comparable to conventional angiography in determining carotid stenosis. Magnetic resonance angiography tended to demonstrate a higher level of stenosis when there was a discrepancy. These data demonstrate that magnetic resonance angiography is a steadily improving technology. Although additional studies need to be done, it seems clear that magnetic resonance angiography will be an imaging modality comparable in accuracy to conventional angiography.

Aged↗
PubMed1991

Effect of cooling rate on the survival of frozen wood frogs, Rana sylvatica.

Wood frogs (Rana sylvatica) were frozen to -2.5 degrees C under five distinct cooling regimes to investigate the effect of cooling rate on survival. Frogs survived freezing when cooled at -0.16 degrees C.h-1 or -0.18 degrees C.h-1, but mortality resulted at higher rates (-0.30 degrees C.h-1, -1.03 degrees C.h-1, and -1.17 degrees C.h-1). Surviving frogs in the latter groups required longer periods to recover, and transient injury to the neuromuscular system was evident. Some of the frogs that died had patches of discolored, apparently necrotic skin; vascular damage, as indicated by hematoma, also occurred. It is concluded that slow cooling may be critical to the freeze tolerance of wood frogs. Additional studies examined the effect of cooling rate on physiological responses promoting freeze tolerance. Mean glucose concentrations measured in plasma (15-16 mumol.ml-1) and liver (42-45 mumol.g-1) following a 2-h thaw did not differ between slowly- and rapidly-cooled frogs but in both groups were elevated relative to unfrozen controls. Thus, freezing injury to rapidly-cooled frogs apparently was not mitigated by the presence of elevated glucose. Water contents of liver tissue, measured 2 h post-thawing, did not differ between slowly-cooled (mean = 77.6%) and rapidly-cooled (mean = 78.5%) frogs. However, the mean hematocrit of slowly-cooled frogs (48%) was significantly higher than that (37%) of frogs cooled rapidly, possibly owing to differences in the dynamics of tissue water during freezing.

Animals↗
PubMed1991

Herpes simplex virus hepatitis after solid organ transplantation in adults.

Twelve patients developed herpes simplex (HSV) hepatitis a median of 18 days after solid organ transplantation. This is earlier than cytomegalovirus hepatitis, which usually occurs 30-40 days after transplantation. Eight recipients (67%) died, and in seven, the diagnosis was made at autopsy or less than 48 h before death. Clinical manifestations associated with mortality were hypotension, disseminated intravascular coagulation (DIC), metabolic acidosis, gastrointestinal bleeding, and bacteremia. Laboratory abnormalities at diagnosis associated with mortality were high creatinine, low platelet counts, prolonged partial thromboplastin time, and a high percentage of band forms on the blood smear. Disseminated HSV disease was noted in four of six patients who had an autopsy and included involvement of lungs in three and the gastrointestinal tract in three. Five recipients developed DIC and all died. Pathologically, HSV hepatitis has two forms, focal and diffuse. All three patients with diffuse liver pathology died. However, three of seven with focal liver pathology survived with antiviral therapy, which suggests that early diagnosis and treatment may be lifesaving. None of these patients had received prophylactic acyclovir. It is possible that acyclovir prophylaxis may be able to prevent this disease.

Adult↗
PubMed1991

A case of nonneurologic Gaucher's disease that biochemically resembles the neurologic types.

Systemic findings such as hepatosplenomegaly and typical Gaucher storage cells in a bone marrow aspirate led to the clinical diagnosis of Gaucher's disease in the seven-year old patient described in this report. On the basis of the lack of neurologic involvement the child was classified as having the Type 1, nonneurologic form of Gaucher's disease. After splenectomy glucocerebrosidase was extracted from her spleen for biochemical analysis. As expected, a marked deficiency of glucocerebrosidase activity was evident in the splenic extract, however her enzyme displayed anomalous behavior compared to other identical splenic preparations from documented Type 1 Gaucher's disease patients in that it failed to reconstitute with the acidic lipid phosphatidylserine. Using the polymerase chain reaction (PCR)-based color complementation assay and restriction endonuclease analysis, we compared the mutation genotype of this child with that of five other classical Type 1 patients. This analysis revealed that our patient alone was homoallelic for a T----C transition at position 1448 in the glucocerebrosidase cDNA that results in a 444Leu----Pro substitution in the glucocerebrosidase protein. The latter mutation genotype is normally associated with the neurologic phenotype, namely, the Types 2 and 3 forms of the disease. The relevance of the nature of polarity in clinical and biochemical analyses is discussed with regard to the phenotypic classification and the future clinical course of disease in the child.

Child↗
PubMed1991

Freeze-thaw injury in erythrocytes of the freeze-tolerant wood frog, Rana sylvatica.

Erythrocytes from the freeze-tolerant wood frog (Rana sylvatica) were subjected to in vitro tests of freeze tolerance, cryoprotection, and osmotic fragility. The responses of cells from frogs acclimated to 4 or 15 degrees C were similar. Erythrocytes that were frozen in saline hemolyzed at -4 degrees C or lower. The addition of high concentrations (150 and 1,500 mM) of glucose or glycerol, cryoprotectants produced naturally by freeze-tolerant frogs, significantly reduced cell injury at -8 degrees C, but concentrations of 1.5 or 15 mM were ineffective. Hemolysis was reduced by 94% with 1,500 mM glycerol and by 84% with 1,500 mM glucose; thus glycerol was the more effective cryoprotectant. Mean fragility values for frog erythrocytes incubated in hypertonic and hypotonic saline were 1,938 and 49 mosM, respectively. Survival in freeze tolerance and cryoprotection experiments was comparable for erythrocytes from frogs and humans, suggesting that these cells may respond similarly to freezing-related stresses. However, the breadth of osmotic tolerance, standardized for differences in isotonicity, was greater for frog erythrocytes than for human erythrocytes. Our data suggest that erythrocytes from R. sylvatica are adequately protected by glucose under natural conditions of freezing and thawing.

Animals↗
PubMed1991

Glucose loading prevents freezing injury in rapidly cooled wood frogs.

The wood frog (Rana sylvatica) is the most commonly studied of ten species of freeze-tolerant vertebrates. Under natural (i.e., slow) rates of cooling, freezing initiates the production of the cryoprotectant glucose, which is mobilized from the liver and distributed to tissues throughout the body. Rapid cooling during freezing is injurious to wood frogs, probably because cryoprotectant production and mobilization are inhibited. To test this hypothesis, we investigated whether rapid-cooling injury is reduced if exogenous glucose is experimentally introduced to tissues before freezing. Glucose-loaded and control (saline-injected) wood frogs were rapidly cooled during freezing to -2.5 degrees C and subsequently assayed for injury at both cellular (erythrocyte) and neuromuscular (behavioral reflex) levels. Rapid cooling produced substantial hemolysis in control frogs, but erythrocyte injury was significantly reduced in glucose-loaded frogs. Similarly neuromuscular injury was significantly higher in control frogs than in glucose-loaded frogs. These findings suggest that rapid-cooling injury results from an inadequate production and distribution of endogenous glucose during freezing. Furthermore, the inverse relationship between the degree of freezing injury and the quantity of exogenous glucose present strongly implicates glucose as a cryoprotectant in R. sylvatica.

Animals↗
PubMed1991

Targeting, dosimetry, and radioimmunotherapy of B-cell lymphomas with iodine-131-labeled LL2 monoclonal antibody.

Sixteen patients with non-Hodgkin's lymphoma were infused with 6.2 to 58.2 mCi (0.2 to 3.9 mg) doses of radioactive iodine (131I)-labeled LL2 immunoglobulin G (IgG) or F(ab')2, in order to study antibody distribution, pharmacokinetics, dosimetry, toxicity, tumor targeting, and therapy. LL2 is a murine IgG2a monoclonal antibody (MAb) reactive with B cells and non-Hodgkin's B-cell lymphoma. In a series of five assessable therapy patients, doses as small as 30 mCi 131I-LL2 IgG or F(ab')2 resulted in tumor responses (two partial remissions, two mixed and minor responses, and one no response), while one patient receiving diagnostic doses as low as 6.2 mCi showed a partial remission for 1 year and a complete remission after a second low radiation dose. No acute toxicities were noted, and only myelotoxicity accompanied therapeutic doses, with grade IV marrow toxicity seen in three of seven patients receiving total doses of about 50 mCi. Dosimetry calculations showed spleen and tumor dose rules of about 4.6 cGy/mCi, which was three to four times the dose to other organs. Despite the administration of relatively low doses of LL2 (0.2 to 3.9 mg), 82% of 60 known extrasplenic lymphoma sites were imaged. Serum clearance showed an average distribution half-life (T1/2) of 2.1 hours and an elimination T1/2 of 32.0 hours. The average total-body clearance T1/2 was 43 to 45 hours. LL2's antigenic target does not appear to be shed in high amounts into the circulation. Three of eight patients having at least two injections showed a human antimouse antibody response. These patients may have been presensitized to animal protein. An interesting observation in this study was the marked drop in circulating B lymphocytes after the administration of radioiodinated LL2 or anticarcinoembryonic antigen MAbs, suggesting that this is a nonspecific radiation effect and not necessarily related to the binding of MAb to normal B cells.

Adult↗
PubMed1990

Murine monoclonal antibodies against carcinoembryonic antigen: immunological, pharmacokinetic, and targeting properties in humans.

We have examined three 131I-labeled murine monoclonal antibodies (MAbs) against carcinoembryonic antigen (CEA), NP-2, NP-3, and NP-4, after i.v. injection in patients with diverse cancers. Although the MAbs had a similar tumor-targeting ability, several important features were discovered that have led us to the selection of one of these MAbs for further clinical evaluation. We found that it is important to evaluate MAbs with a high immunoreactivity. For example, the MAb NP-2 was used initially in patients with an immunoreactivity between 35 and 50%. Although the tumor-imaging properties of this MAb compared favorably with the affinity-purified, goat anti-CEA antibody that we used previously, further purification of NP-2 to an immunoreactivity greater than 70% uncovered a previously unknown cross-reactivity with human granulocytes. It was also discovered that the MAbs differed in their ability to complex with CEA in the blood. Plasma samples were analyzed by gel filtration at 1 or 24 h after injection. The formation of complexes with circulating CEA was dependent on the CEA:MAb ratio in the blood. NP-3 complexed to a greater degree with CEA than NP-4, but NP-2 did not complex with CEA even at CEA:NP-2 ratios of 55 to 1. NP-3 commonly showed enhanced uptake in the colon by external scintigraphy, and examination of the radioactivity in the stool showed that most of the radioactivity was associated with whole IgG and large-sized fragments of NP-3. We also compared the rate of elimination of radioactivity from the blood for all of the MAbs and compared the clearance of NP-3 to NP-4 at three different ranges of MAb protein doses (less than 1.0 mg, 1 to 5 mg, and 5 to 20 mg). The blood clearance rate for NP-3 was fastest among the other MAbs at protein doses exceeding 1.0 mg. Patients given less than 1.0 mg of NP-4 had a significantly (P less than 0.005) shorter elimination half-life than patients given more than 1.0 mg of NP-4. By virtue of NP-4's good targeting properties in patients and its limited complexation with circulating CEA, it was selected as the MAb of choice for CEA tumor imaging.

Animals↗
PubMed1990

Tumor, red marrow, and organ dosimetry for 131I-labeled anti-carcinoembryonic antigen monoclonal antibody.

Tumor-, red marrow-, and organ-absorbed doses were calculated for patients receiving 131I-labeled monoclonal antibodies against carcinoembryonic antigen for either diagnosis or therapy. Ten patients with confirmed liver tumors who received doses ranging from 10.79 to 200 mCi were evaluated. Urine and blood samples were taken in order to determine total body and red marrow activity, respectively. Anterior and posterior gamma camera images were obtained at multiple times postinjection in order to quantitate activity uptake using the conjugate view counting method for the following organs and regions: lungs, liver, spleen, kidneys, and the liver tumors. In addition, sacral regions of interest were drawn to generate red marrow-absorbed dose estimates for comparison to those obtained by blood sampling. Tumor volumes were obtained from volumetric analysis of the patient's computed tomographic study and tumor S values were obtained by assuming uniform distribution of the 131I-labeled monoclonal antibody in spherical tumor regions considering all emitted electrons, beta-particles, and photons. The following mean absorbed doses in rads/mCi injected were obtained: lungs, 2.3 +/- 1.6 (SD); liver, 1.4 +/- 0.7; spleen, 2.6 +/- 1.4; kidneys, 3.1 +/- 1.5; total body, 0.7 +/- 0.5; red marrow from blood sampling, 2.9 +/- 1.9; red marrow from sacral scintigraphy, 1.7 +/- 1.2; and liver tumors, 69.3 +/- 92.5. Tumor volumes ranged from 1 to 216 g and the percentage of uptake/g of monoclonal antibody into these tumors ranged from 0.0006 to 1.040. There was a statistically significant difference between the two techniques for estimation of red marrow dose (P less than 0.01). This methodology, permits calculation of tumor, red marrow, and organ dosimetry using planar gamma camera imaging.

Antibodies, Monoclonal↗
PubMed1990

Clinical studies of cancer radioimmunodetection with carcinoembryonic antigen monoclonal antibody fragments labeled with 123I or 99mTc.

Seventy-three patients with diverse cancers containing carcinoembryonic antigen received 123I-labeled anti-carcinoembryonic antigen monoclonal antibody F(ab')2 fragment [38 patients], 99mTc-labeled anti-carcinoembryonic antigen monoclonal antibody Fab' fragment [23 patients], or both reagents at different times [6 patients] for evaluation of antibody targeting and imaging [radioimmunodetection (RAID)], using planar and single-photon emission computed tomography. The results indicated that antibody fragments are preferred for early tumor imaging (within 24 h). Rapid targeting and clearance from blood and normal organs of the antibody fragments (blood median t1/2 elimination of 26.5 and 13.2 h for the F(ab')2 and Fab' fragments respectively) permitted the use of short-lived radionuclides, such as 123I (13.3 h) and 99mTc (6 h), and confirmed that selective antibody accretion in tumors occurred very soon after administration, such as between 2 and 5 h. Scan interpretations at 24 h for the 123I-labeled F(ab')2 and at 2-5 h for the 99mTc-labeled Fab' revealed overall sensitivities, on a tumor site basis, of 95.9 and 94.9%, respectively. On a site basis, the overall accuracies were 94.2 and 93.8% for the 123I and 99mTc immunoconjugates, respectively. In the 6 patients studied with both radioimmunoconjugates, a high concordance in detection was found. Both imaging agents also revealed a high number of putatively new tumor sites not disclosed by other radiological methods at the time of the RAID studies, of which 40.0 and 20.5% were subsequently confirmed as tumor for the 123I and 99mTc agents, respectively, within an 11-month follow-up period. This represented 24 proven occult tumor sites in 19 patients given the 123I-immunoconjugate and 16 proven occult tumor sites in 9 patients receiving the 99mTc agent. The new lesions were found up to 17 and 7 months earlier for 123I-RAID and 99mTc-RAID, respectively, than with other detection methods. The smallest tumors identified were below 0.5 cm, especially with the 99mTc immunoconjugate and single-photon emission computed tomography imaging. The findings of this study confirm previous evidence that RAID is a safe and a potentially useful new method of cancer detection. Despite the excellent results with the 123I-F(ab')2 antibody fragment, its poor availability and high cost limit its clinical use. Therefore, the 99mTc agent, which is made by an instant, 1-step, 1-vial, direct labeling method, appears to be the method of choice for rapid and accurate detection of cancer by RAID.

Adolescent↗
PubMed1990

A haemodynamic evaluation of the femoro-femoral cross-over bypass.

The femoro-femoral cross-over bypass has become a popular choice for the management of unilateral iliac artery disease, being used in preference to aorto-femoral or extraperitoneal ilio-femoral bypasses. It is a relatively minor procedure and associated with a small incidence of side effects, the main one being the risk of development of a steal of blood from the donor limb by the bypass. Although this problem has been widely discussed, haemodynamic studies have been limited by the use of indirect measurements of blood flow, such as ankle systolic pressures or by the use of electromagnetic flowmetry at the time of surgery. No study employing volumetric blood flow measurements to identify and quantify blood steal in the postoperative patient has been reported to date. With aims of studying the haemodynamic effects of a femoro-femoral cross-over bypass on the circulation in both the recipient and donor limbs, and of identifying preoperatively, problems likely to lead to haemodynamic problems or to graft failure, the present study of 31 patients undergoing femoro-femoral bypass was undertaken. The patients, 18 of whom had rest pain and 13 intermittent claudication, were studied preoperatively using arteriography and a non-invasive assessment. At 3 months from the operation, all received a clinical assessment and a further non-invasive assessment, including a measurement of blood volume flow. Flow measurements were made in the bypass at rest and during a reactive hyperaemia test. In addition, flow measurements were made in the donor limb below the bypass origin at rest and during hyperaemic testing of the recipient limb in order to assess any steal effect the bypass might cause to the donor limb circulation. All 31 patients were improved by surgery, but five developed donor limb claudication which was attributed to steal in three cases. Resting blood flow in the bypasses, 161 (65-282)ml/min [median (range)], rose by 116% (5-428%) to 300 (82-1114)ml/min after hyperaemic testing. Simultaneously, bypass hyperaemia caused a fall in donor limb blood flow of 32% (0-74%). Of the preoperative non-invasive tests, only donor femoral artery pulse rise time was related to the later development of objective evidence of steal. Successful Gruntzig dilatation of four major stenoses resulted in a satisfactory outcome.

Adult↗