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Biomedical subjects

J Freeman

Publications and source records attributed to J Freeman.

At least 127 records · Page 7Linked to original sources
PubMed1994

Liver transplantation following preoperative closure of intrapulmonary shunts.

Intrapulmonary shunts producing basal resting hypoxemia and necessitating the continual use of supplemental oxygen by two cirrhotic men were closed prior to liver transplantation with octreotide acetate, a somatostatin analogue. The closure of these shunts was monitored by serial blood gas determinations and shunt estimations using two different techniques. Partial closure of the shunts with preoperative octreotide acetate administration allowed liver transplantation to proceed with successful engraftment and eventual permanent closure of the shunts. Currently, both patients are alive and well with normal liver function and blood gases and, most important, have no requirement for supplemental oxygen.

Adult↗
PubMed1993

Giftedness.

Explore the source record for details and available documents.

Child↗
PubMed1993

Quantitative comparison between the transplantability of human and murine tumors into the subcutaneous tissue of NCr/Sed-nu/nu nude and severe combined immunodeficient mice.

In previous reports, nude mice have demonstrated residual immunoreactivity against xenografts. Severe combined immunodeficient (SCID) mice lack functional T- and B-cells. These animals are expected to be better hosts in which to perform preclinical studies on human tumors. The purpose of this study is to quantitate the advantage of SCID mice over nude mice in terms of transplantability of human and murine tumors and the importance of residual immunity in SCID mice. The transplantation assays are described by an assay based on the number of tumor cells required to transplant tumor into 50% of recipients (TD50). Seven human tumors of different histology and four murine tumor cell lines were used. Serial 2-10-fold dilutions of cells were injected (0.1 ml) into the flanks of normal and whole-body irradiated WBI nude and SCID mice. The results showed that in 6 of 6 human tumor cell lines studied, TD50S for SCID mice were 2.4 to 200 times lower than that of nude mice (significant in 5 cell lines). In contrast, in 2 of 3 murine tumors, TD50S in WBI SCID mice were significantly higher than that found in nude mice. When SCID and nude mice received WBI, TD50S were lower than those of nonirradiated animals in 5 of 5 xenografts (significant in 2 cell lines for nude mice and in 5 cell lines for SCID mice). We concluded that WBI SCID mice are significantly better recipients of human tumor xenografts than nude mice. There is a factor of 10-1625 gain in TD50S in favor of the WBI SCID mice when compared to nonirradiated nude mice. WBI has, however, an important effect on SCID mice which may suggest a detectable residual immunoreactivity, perhaps due to natural killer cells. These data demonstrate that WBI SCID mice are better models for human tumor transplantation that nude mice and, although WBI at 6 Gy suppressed significantly the immune system of nude mice, a certain level of immunoreactivity against xenografts is still maintained.

Animals↗
PubMed1993

Quantitative comparison between the transplantability of human and murine tumors into the brain of NCr/Sed-nu/nu nude and severe combined immunodeficient mice.

We have demonstrated (A. Taghian et al., Cancer Res., 53: 5012-5017, 1993) that the take rate of human xenografts in the s.c. tissue of severe combined immunodeficient (SCID) mice is significantly higher than that of nude mice. Earlier, this laboratory reported that the transplantability of tumor xenografts was significantly higher for intracranial (i.c.) injection than for s.c. injection in nude mice. The purpose of this study is to assess: (a) the relative i.c. transplantability of human and murine tumors in comparison with s.c. tissue in SCID mice; (b) the relative i.c. transplantability in SCID mice in comparison to nude mice; and (c) the influence of whole-body irradiation on i.c. transplantability of SCID and nude mice. The assay based on the number of cells required to transplant tumors into 50% of recipients (TD50) was used to describe the transplantability assays. Five human and four murine tumor cell lines were used. Concurrent TD50 assays were performed i.c. in whole-body irradiated and nonirradiated SCID and nude mice. Serial 2-10-fold dilutions of cells were injected in a 10-microliters volume into the right parietal lobe 3 mm below the skin. The results showed that in all tumors studied the i.c. TD50S were significantly lower than the s.c. TD50S by a factor of 1.7-1580. The average enhancement ratio (s.c. TD50/i.c. TD50) in nude mice was twice that in SCID mice. No significant difference was found between the i.c. TD50S in SCID and in nude mice, contrary to the significant difference in s.c. TD50S between both strains of mice (A. Taghian et al., Cancer Res., 53: 5012-5017, 1993). Whole-body irradiation did not significantly affect the i.c. TD50 in nude mice; however, it did affect two of three xenografts in SCID mice. In conclusion, despite the significantly lower s.c. TD50S of human xenografts in SCID mice, i.c. TD50S were almost similar to those of NCr/Sed-nu/nu nude mice. This suggests the presence of different immunoreactivities between nude and SCID mice in s.c. transplantability; however, for i.c. transplantability, nude mice behaved equally as well as SCID mice. The significant enhancement ratio in SCID mice is further evidence that this strain of mice displays a residual systemic immunoreactivity, although the immunoreactivity is significantly lower than that of nude mice.

Animals↗
PubMed1993

Impact of stromal sensitivity on radiation response of tumors.

BACKGROUND: Irradiation of tumors causes the death of both parenchymal tumor cells as well as normal tissue stromal cells (e.g., endothelium, connective tissue). However, it has been difficult to distinguish the contributions to overall tumor response after irradiation from the two compartments. The development of the severe combined immunodeficient (SCID) mouse provides a model in which the contribution of stromal cell responses to ionizing radiation to overall tumor response can be defined, because its normal tissue cells are extremely radiosensitive. Therefore, the results of irradiation of tumors in radiation-sensitive (SCID) and radiation-resistant hosts can be compared, and the contribution of the normal tissue stroma clarified. PURPOSE: Our purpose was to investigate the effects of radiation-induced stromal cell damage on tumor cell death, using tumor growth delay (GD) and local control (complete and permanent regression of the irradiated tumor) as end points. METHODS: Tumor GD and local control experiments were performed in SCID, athymic, and C3H mice. Sixty SCID and 60 nude mice for each of three human tumor cell lines (HGL9, HSTS26, HCT15) and for each of five murine cell lines (FSC1, FSC2, FSM1, FSM2, E01) and 60 SCID and 60 C3H mice for the FSa2 spontaneous C3H sarcoma were studied. Neoplasms were produced by injection of 10(6) cells from in vitro tissue cultures into the flanks of donor mice; after tumors had grown, experimental neoplasms were produced by transplanting 2- to 3-mm fragments into recipient mice. Animals were randomly assigned to various groups when tumors reached average volumes of 120 mm3. Graded, single-dose x irradiations (15-115 Gy, dose rate about 7 Gy/min) were given under acutely hypoxic conditions. Tumors were scored one to two times per week until recurrence. RESULTS: The x-ray doses needed to achieve local control in 50% of the animals (tumor control doses, TCD50) ranged from 45.1 to 58.0 Gy for human tumors and from 36.3 to 114.0 Gy for murine tumors. On average, the TCD50 values in SCID mice were only about 3.5% lower than values in nude or C3H mice. The amount of GD defined at 66% of the TCD50 for the various groups was, however, 27% longer in the SCID mice (P = .004). CONCLUSIONS: While the three-fold higher radiation sensitivity of the normal tissue stromal cells in the SCID mice did not alter the percentage of tumors controlled by x irradiation in the SCID mouse hosts as compared with other hosts, there appear to be significant differences in GD. Radiation-induced stromal cell damage does not significantly contribute to tumor cell death; however, it can prolong the interval of tumor regression.

Animals↗
PubMed1993

Placental and fetal Doppler velocimetry in pregnancies complicated by maternal diabetes mellitus.

OBJECTIVE: Our purpose was to investigate placental and fetal circulation in pregnancies complicated by maternal diabetes mellitus and to relate any changes to fetal blood pH, Po2, and hematocrit. STUDY DESIGN: Doppler measurements of both uterine arteries, one umbilical artery, the fetal descending thoracic aorta, and one fetal middle cerebral artery were performed in 65 well-controlled diabetic pregnancies in a cross-sectional study at the Harris Birthright Research Centre for Fetal Medicine, London. In 41 cases cordocentesis was also performed for the measurement of umbilical venous blood pH, Po2, and hematocrit. RESULTS: The mean umbilical venous blood pH was significantly lower and the hematocrit significantly higher than the appropriate normal mean for gestation. However, the Doppler indices of the placental and fetal circulations were essentially normal, except in some of the cases complicated by preeclampsia or intrauterine growth retardation. CONCLUSIONS: Maternal diabetes mellitus is not associated with abnormalities in Doppler indexes of the placental or fetal circulations.

Blood Flow Velocity↗
PubMed1993

Functional and morphological-occlusal aspects in children treated for unilateral posterior cross-bite.

Morphological and functional aspects were investigated in children with unilateral posterior cross-bite (UPXB) before and after treatment. Sixty-five patients with Class I malocclusion with UPXB in the mixed dentition stage (mean age 8.8 +/- 1.6 years) served as the experimental group and 10 children of comparable age, with normocclusion or very mild Class I malocclusion (without UPXB) served as controls. The morphological aspects were examined on a longitudinal basis while the functional recordings, by means of a sirognathograph, were performed in a cross-sectional fashion. Complete elimination of cross-bite was maintained in 61 per cent and was accompanied by a dramatic reduction in the prevalence of functional mandibular displacement. However, the prevalence of mandibular midline deviation related to the maxillary midline as recorded in the intercuspal position was not affected. In addition, the high prevalence of Class II subdivision relationships which accompanied the UPXB in the intercuspal position was resolved in 50 per cent of the cases only. The sirognathographic recordings of the masticatory pattern showed a very high prevalence of a 'reverse sequencing' type pattern before treatment which was significantly lower following the elimination of UPXB, but still notably higher when compared with the controls. Reasons for these results are suggested and possible inter-relationships between the morphological and functional aspects are discussed.

Child↗
PubMed1993

An evaluation of a new self-adhesive patch preparation of amethocaine for topical anaesthesia prior to venous cannulation in children.

A new preparation of amethocaine in the form of a self-adhesive patch, designed to provide topical cutaneous anaesthesia prior to venous cannulation, was evaluated in an open study of 189 children. The new preparation of amethocaine was in place for a mean time of 48 min (SD 3.9). Eighty percent of patients had a satisfactory degree of analgesia for venous cannulation. Nine percent of patients experienced moderate pain and 11% experienced severe pain during venous cannulation. In 26% of patients there was slight (24%) or moderate (2%) erythema at the site of application, and in 5% slight oedema was noted at the site of application. Eight percent of patients had slight itching and 1% had moderate itching at the site of application. There was a clinical impression that venous dilatation made cannulation easier than with EMLA cream. These results suggest that this convenient preparation of amethocaine is highly effective at providing adequate topical cutaneous anaesthesia with a short onset time and a low incidence of minor side effects with no evidence of systemic toxicity.

Administration, Cutaneous↗
PubMed1993

Prediction of fetal acidaemia in pregnancies complicated by maternal diabetes mellitus by biophysical profile scoring and fetal heart rate monitoring.

OBJECTIVE: To determine whether computer assisted fetal heart rate analysis or the biophysical profile score can provide noninvasive prediction of fetal acidaemia. DESIGN: Cross sectional study. SETTING: Harris Birthright Research Centre for Fetal Medicine, King's College Hospital School of Medicine, London. SUBJECTS: Forty-one women with pregnancies complicated by diabetes mellitus. INTERVENTIONS: Fetal heart rate (FHR) monitoring with computer assisted analysis, biophysical profile score (BPS) and cordocentesis for measurement of umbilical venous blood glucose concentration and blood gases, up to 24 h before delivery at 27 to 39 weeks gestation. RESULTS: The mean umbilical venous blood pH was significantly lower than the normal mean for gestation, and was below the 5th centile in 18 pregnancies, including all six cases where the mother had nephropathy and hypertension. The mean pO2 was not significantly different from the normal mean for gestation. There were significant associations between fetal acidaemia and both the BPS (r = 0.46, P < 0.01) and FHR variation (r = 0.42, P < 0.01). However, of the 12 acidaemic fetuses of non-nephropathic mothers, nine had normal BPS and six had normal FHR variation. CONCLUSIONS: In pregnancies complicated by maternal diabetes mellitus, BPS and FHR variation are of limited value in the prediction of fetal blood pH.

Acidosis↗
PubMed1993

Proliferating cell nuclear antigen (PCNA) and nucleolar organiser regions in Hodgkin's disease: correlation with morphology.

AIM: To define the distribution of proliferating cell nuclear antigen (PCNA) and silver staining nucleolar organiser regions (AgNORs) in Hodgkin's disease. METHODS: PCNA was shown in a series of 34 cases of Hodgkin's disease using immunohistochemical methods. In a second series of 46 cases the AgNOR technique for interphase nucleolar organiser regions was studied. Both series comprised routinely fixed and processed paraffin wax sections of three main Rye subtypes. RESULTS: In all cases, regardless of Rye subtype, most Sternberg-Reed cells and mononuclear Hodgkin cells showed nuclear PCNA immunoreactivity and such cells had 15 or more AgNOR sites. The Hodgkin cells had, in general, about half the number of AgNORs seen in Sternberg-Reed variants. CONCLUSIONS: These data support the notion that Hodgkin's disease can be regarded as a high grade lymphoma, the large Hodgkin's and Sternberg-Reed cells being the (PCNA positive and AgNOR rich) neoplastic elements with high proliferative capacity. A smaller proportion of the associated cells also showed evidence of proliferation.

Antigens, Neoplasm↗
PubMed1992

A noninvasive method of predicting pulmonary-capillary wedge pressure.

BACKGROUND: The noninvasive prediction of pulmonary-capillary wedge pressure (PCWP) is important for the recognition and treatment of a variety of cardiovascular disorders. The response of the arterial pressure to the Valsalva maneuver has been shown to correlate with the PCWP. We therefore devised a noninvasive method to measure this pressure response at the bedside and correlated these measurements with the PCWP measured directly with a pulmonary-artery catheter. METHODS: Simultaneous, blinded, noninvasive measurements of the ratio of the final amplitude to the initial amplitude of the pulse wave form during the stress phase of the Valsalva maneuver (pulse-amplitude ratio) and direct measurements of the PCWP were obtained in 20 clinically stable patients and in 14 clinically unstable patients who were receiving vasoactive agents, 12 of whom also had endotracheal tubes in place. RESULTS: Using linear regression analysis, we found that the pulse-amplitude ratio strongly correlated with the measured PCWP over a range of base-line values from 4 to 32 mm Hg for the 20 clinically stable patients (R2 = 0.80) and the 14 clinically unstable patients (R2 = 0.85). The method also correctly predicted changes in the PCWP after the administration of nitroglycerin or furosemide and after expansion of the intravascular volume (R2 = 0.79). CONCLUSIONS: These preliminary data indicate that a simple noninvasive method can accurately predict the PCWP and changes in the PCWP in response to medical therapy.

Blood Pressure↗
PubMed1992

Tumors arising in SCID mice share enhanced radiation sensitivity of SCID normal tissues.

We addressed the question of whether cancers arising in an abnormally radiation sensitive normal tissue are also abnormally sensitive to ionizing irradiation. Germ line mutation-carrying mice with an enhanced radiation sensitivity of the normal tissue, the severe combined immunodeficient (SCID), and normally radiation sensitive mice (C3H) were used to study the sensitivity of normal and tumor tissues in vivo and in vitro. The lethal dose for 50% of the irradiated animals after single dose whole body irradiation was 2.6-fold higher in C3H compared to SCID mice. The dose for an isoeffective acute skin reaction after single dose irradiation was end point dependent 1.7 to 3.7 times higher in C3H than in SCID mice. Embryonic fibroblast and methylcholanthrene induced soft tissue sarcomas derived from C3H and SCID mice were established in vitro and colony-forming assays after single dose irradiation were carried out. Choosing mean inactivation dose as the end point, SCID fibroblast lines were 3.0-fold and SCID tumor cell lines 2.7-fold more radiation sensitive than C3H fibroblast lines and C3H tumor cell lines. Tumor control and growth delay assays for 110-mm3 tumors were used to compare the radiation sensitivity of SCID and C3H tumors in vivo. The doses for 50% local tumor control and a growth delay of 40 days were 2.6 times higher in C3H tumors compared to SCID tumors. Tumors arising in an abnormally radiation sensitive normal tissue are also sensitive to irradiation. The difference in radiation sensitivity of normal tissues predicted the difference in tumor tissues in these two murine systems.

Animals↗
PubMed1992

High expression of transforming growth factor-beta long cell cycle times and a unique clustering of S-phase cells in patients with acute promyelocytic leukemia.

Expression of transforming growth factor-beta (TGF-beta), which inhibits the proliferation of hematopoietic progenitors, was investigated simultaneously with cell cycle characteristics in 63 bone marrow biopsies from 23 cases with acute promyelocytic leukemia (APL). Bromodeoxyuridine (BrdU) was administered to every patient (17 newly diagnosed) for determination of the labeling index (LI) and the durations of S-phase (Ts) and the cell cycle (Tc) of leukemic promyelocytes. APL cases had lower LI both in the bone marrow aspirate (6.1% v 11.4%, P = .008) and biopsy (21.1% v 28.0%, P = .001) and longer Tc (93.6 hours v 56.0 hours, P = .002) when compared with other French-American-British subtypes. TGF-beta expression (detected by a monoclonal anti-TGF-beta 2/beta 3 antibody) was dramatically high, especially in interstitial areas of the biopsies. S-phase cells were found as geographically restricted islands of proliferation (GRIPs) in 20 of 22 cases. Weekly biopsies showed an increment in TGF-beta on day 7 of therapy in 13 of 17 cases, while in vivo differentiation was noted in 9 of 15. We conclude that the presence of high TGF-beta expression may explain the biologic basis for the slowly cycling nature of leukemic promyelocytes in APL as well as the unique clustering of S-phase cells observed in GRIPs.

Adult↗
PubMed1992

Abnormal regulation of the myc gene in myeloid leukemia.

To study the regulation of expression of the myc protooncogene, cells from normal individuals and patients with acute myelogenous leukemia (AML), and chronic phase and blastic crisis of chronic myeloid leukemia (CML) cells were put in overnight culture in the presence or absence of fetal calf serum. Myc expression in normal marrow cells and chronic phase CML cells fell after culture in vitro. In contrast, myc expression was maintained or increased in a majority of the AML and blastic crisis CML specimens. These data demonstrate that the regulation of myc expression is disordered in many AML and blastic crisis specimens but not in chronic phase CML cells.

Base Sequence↗
PubMed1992

Cutaneous copper and zinc losses in burns.

To measure the exudative cutaneous copper (Cu) and zinc (Zn) losses in burns, 10 patients, aged 36 +/- 9 years (mean +/- s.d.) with burns covering 33 +/- 10 per cent of the total body surface area, were studied from the first postburn day (D1) until D7. All intakes and losses were analysed for Cu, Zn and nitrogen (N) content. Cutaneous losses were extracted from textiles surrounding the patients. Urinary excretions were 0.12 +/- 0.06mg/24h for Cu, 0.9 +/- 0.6mg/24h for Zn, and 14.1 +/- 4.4g/24h for N. Mean daily exudative losses through wound seepage from D1 to D7 were 4.7 +/- 2.1mg/24h for Cu, 27.1 +/- 14.4mg/24h for Zn, and 8.7 +/- 3.8g/24h for N. The cumulated mean losses over 7 days were 37mg for Cu, and 212mg for Zn, representing respectively 20-40 per cent and 5-10 per cent of normal body content. Serum Cu and Zn levels were strongly depressed. The urinary Cu/N ratios correlated with clinical improvement. We conclude that the exudative Cu and Zn losses during the first week postburn contribute significantly to the increased nutrient requirements in burns.

Adult↗