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Biomedical subjects

W P Thorpe

Publications and source records attributed to W P Thorpe.

14 recordsLinked to original sources
PubMed1998

Objective estimates of the probability of death from burn injuries.

BACKGROUND: Over the past 20 years, there has been remarkable improvement in the chances of survival of patients treated in burn centers. A simple, accurate system for objectively estimating the probability of death would be useful in counseling patients and making medical decisions. METHODS: We conducted a retrospective review of all 1665 patients with acute burn injuries admitted from 1990 to 1994 to Massachusetts General Hospital and the Shriners Burns Institute in Boston. Using logistic-regression analysis, we developed probability estimates for the prediction of mortality based on a minimal set of well-defined variables. The resulting mortality formula was used to determine whether changes in mortality have occurred since 1984, and it was tested prospectively on all 530 patients with acute burn injuries admitted in 1995 or 1996. RESULTS: Of the 1665 patients (mean [+/-SD] age, 21+/-20 years; mean burn size, 14+/-20 percent of body-surface area), 1598 (96 percent) lived to discharge. The mean length of stay was 21+/-29 days. Three risk factors for death were identified: age greater than 60 years, more than 40 percent of body-surface area burned, and inhalation injury. The mortality formula we developed predicts 0.3 percent, 3 percent, 33 percent, or approximately 90 percent mortality, depending on whether zero, one, two, or three risk factors are present. The results of the prospective test of the formula were similar. A large increase in the proportion of patients who chose not to be resuscitated complicated comparisons of mortality over time. CONCLUSIONS: The probability of mortality after burns is low and can be predicted soon after injury on the basis of simple, objective clinical criteria.

Adolescent↗
PubMed1995

Dynamics of photoinduced cell plasma membrane injury.

We have developed a video microscopy system designed for real-time measurement of single cell damage during photolysis under well defined physicochemical and photophysical conditions. Melanoma cells cultured in vitro were treated with the photosensitizer (PS), tin chlorin e6 (SnCe6) or immunoconjugate (SnCe6 conjugated to a anti-ICAM monoclonal antibody), and illuminated with a 10 mW He/Ne laser at a 630 nm wavelength. Cell membrane integrity was assessed using the vital dye calcein-AM. In experiments in which the laser power density and PS concentration were varied, it was determined that the time lag before cell rupture was inversely proportional to the estimated singlet oxygen flux to the cell surface. Microscopic examination of the lytic event indicated that photo-induced lysis was caused by a point rupture of the plasma membrane. The on-line nature of this microscopy system offers an opportunity to monitor the dynamics of the cell damage process and to gain insights into the mechanism governing photolytic cell injury processes.

Cell Line↗
PubMed1993

Antibody Targeted Photolysis.

The technique of Antibody Targeted Photolysis (ATPL) is reviewed from an historical perspective with a summary of the literature since the first experiments were performed in 1983. Attention is given to both the biological and photophysical properties of the various immunoconjugates that have been developed. References to critical discoveries and competing technologies in the photodynamic literature are given. Topics include: synthesis of immunoconjugates, in vitro vs. in vivo toxicity, in vivo biodistribution, immunoconjugate delivery, photosensitizer selection based on photophysical properties, light delivery for specific applications, oxygen requirements, and other physicochemical phenomena. A mathematical model of the dynamics for cell killing based upon the transport of phototoxins to the cell surface is developed. A generalized set of coupled differential equations is given, which conveniently summarizes the manifold requirements stressed earlier for successful cell killing. Solutions are then presented for an idealized set of conditions appropriate for an isolated tumor cell. Suggestions for further improvements and follow-up experiments are made that could help in the evolution of ATPL into a useful clinical therapy and/or probe for cell biological studies.

Animals↗
PubMed1986

Osteonecrosis in sickle cell trait.

Osteonecrosis is common in sickle cell anemia but has been rarely reported with sickle cell trait. Two cases of osteonecrosis of the femoral head caused by sickle cell trait are presented. One patient's diagnosis was delayed because the association of osteonecrosis and sickle cell trait was not recognized. The previous reported cases of this association are discussed, emphasizing diagnostic implications for 12 black patients presenting with hip pain.

Adult↗
PubMed1980

Procollagens as markers for the cell of origin of human bone tumors.

Cells derived from osteogenic sarcomas and from Ewing's sarcomas, two malignant bone tumors, were examined for the types of collagens they elaborated into the tissue culture media. Type I procollagen was the predominant species from all osteogenic sarcoma cell lines, a finding consistent with bone cell origin. The Ewing's sarcoma cells contained a prominent peak of type III procollagen and resembled the profile of vascular smooth muscle cells. Fibroblasts derived from skin biopsies taken from amputation specimens synthesized both type I and type III procollagens at the expected ratio of approximately 3:1. The examination of matrix proteins may provide a general classification scheme for human sarcomas and permit distinction of one tumor from another, as well as from normal fibroblasts.

Bone Neoplasms↗
PubMed1979

Prognostic significance of alkaline phosphatase measurements in patients with osteogenic sarcoma receiving chemotherapy.

During the period January 1975 to August 1977, alkaline phosphatase levels in 30 patients with osteogenic sarcoma were closely followed in an attempt to determine if these measurements had clinical value in predicting the course of patients with this disease. Of 17 patients with elevated preoperative alkaline phosphatase levels, 12 recurred. Of 13 patients with normal preoperative alkaline phosphatase levels, only 4 recurred (p less than .05). Thus, alkaline phosphatase levels that were elevated preoperatively were correlated with poor prognosis. A similar correlation between postoperative alkaline phosphatase levels and prognosis could not be made.

Adolescent↗
PubMed1979

A sensitive assay for the detection cytotoxic antibodies to mammalian cell surface antigens.

A microcytotoxicity assay for the detection of complement-dependent serum toxicity against adherent cells has been modified to include post-labeling of the target cells with [3H]leucine or [3H]thymidine. The adaptation represents a significant improvement over the visual counting of residual cells. The technique is more objective and less tedious than the original procedure, while retaining the features of economy of cells and sera, reproducibility, and sensitivity. Examples are given which demonstrate the suitability of the modified assay for the analysis of human and mouse tumor antigens using autologous, allogeneic, and syngeneic sera.

Animals↗
PubMed1979

Split thickness skin grafting of the plantar surface of the foot after wide excision of neoplasms of the skin.

Results of our studies show split thickness skin grafts are an effective cover for plantar surface defects resulting from tumor excision. Long term follow-up studies of these patients revealed no graft failures. The ease with which split thickness skin grafts can be performed makes it the treatment of choice for reconstruction of areas of excison of neoplasms of the skin on the plantar surface of the foot.

Adult↗
PubMed1978

Expression of oncofetal antigens by murine and human normal cells in tissue culture.

Normal mouse tissues in tissue culture express fetal antigens that are not expressed on these same tissues in vivo. The fetal antigens expressed on normal mouse cells in vitro are also expressed on at least two murine sarcomas, and account for the cross-reactive antibodies between these tumors. The fetal antigens are distinct from unique tumor-specific antigens found on these neoplasms. Normal human cells in tissue culture also express antigens found in human fetuses during the first trimester of pregnancy. Many human sera contain natural antibodies directed against the fetal antigens appearing in vitro. The expression of oncofetal antigens by normal cells in tissue culture must be taken into account in the interpretation of results of studies in tumor immunology in which tissue-cultured cells are utilized.

Animals↗
PubMed1977

Technique for extracorporeal resection of dissecting renal arterial aneurysm with renal autotransplantation.

A progressively enlarging dissecting aneurysm of the right renal artery secondary to fibromuscular dysplasia presents a difficult surgical problem. We present a technique of extracorporeal approach for correction of such aneurysm in a patient with dissecting aneurysm and hypertension. This technique utilizes a Teflon patch graft to facilitate the arterial anastomosis of the renal autotransplantation.

Adult↗
PubMed1977

Expression of fetal antigens by normal human skin cells grown in tissue culture.

Normal human sera are capable of causing complement-mediated lysis of normal human skin cells grown in tissue culture. This lytic reactivity can be completely removed by absorption with first trimester fetal tissue. Absorption with a variety of normal adult human tissues including lymphocytes, decidua, skin, and muscle are incapable of absorbing reactivity. Absorption of reactivity by fetal tissue is specific and not due to the introduction of anti-complementary or other nonspecific factors, as evidenced by the inability of simultaneous fetal absorption to remove reactivity from antisera with specificity for HLA antigens. Similarly, absorption of lytic sera with fetal calf serum proteins was incapable of removing reactivity against normal cells in tissue culture. It thus appears that normal human cells in tissue culture express antigens shared by the first trimester human fetus, but not present on a variety of adult human tissues. This "neoantigen" present on normal human cells when grown in tissue culture is a potential source of confusion and must be accounted for in searching for human tumor-specific antigens utilizing tissue culture cells.

Antigens↗
PubMedDate not supplied

Antibody-targeted photolysis: in vitro immunological, photophysical, and cytotoxic properties of monoclonal antibody-dextran-Sn(IV) chlorin e6 immunoconjugates.

A set of anti-melanoma immunoconjugates were prepared which contained chlorin e6: antibody molar ratios of 18.9:1, 11.2:1, 6.8:1, and 1.7:1. All immunoconjugates retained antigen binding activity regardless of the chromophore:antibody substitution ratio that was attained. In contrast, the ground-state absorption spectra of the immunoconjugates showed features which appeared to be dependent on the chromophore:antibody molar ratio. In addition, the quantum yield of singlet oxygen generated by the conjugated chromophores was observed to be significantly less than that observed with the unbound dye. Time-resolved absorbance spectroscopy of the chromophore excited triplet state indicated that the loss of singlet oxygen quantum yield resulted from diminished chromophore triplet yield. Analysis of data obtained from in vitro photolysis of target melanoma cells, in combination with that obtained from the immunochemical and photochemical studies, indicates that the observed immunoconjugate phototoxicity can be reasonably quantitatively represented by (1) the ability of the immunoconjugate to bind SK-MEL-2 cell surface antigen, (2) the amount of chromophore localized at the target cells by immunoconjugate binding, (3) the delivered dose of light at 634 nm, and (4) the singlet oxygen quantum yield of the antibody-bound photosensitizer. Though these data argue strongly for photolysis by the cumulative dosage of singlet oxygen at the cell membrane, nonetheless, the concurrent photoinduced release of other cytotoxic agents should not be ruled out.

Antibodies, Monoclonal↗