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Biomedical subjects

F Thomas

Publications and source records attributed to F Thomas.

At least 235 records · Page 13Linked to original sources
PubMed1989

Promotion of incompatible allograft acceptance in rhesus monkeys given posttransplant antithymocyte globulin and donor bone marrow. II. Effects of adjuvant immunosuppressive drugs.

Previous studies from this laboratory demonstrated prolonged acceptance of MHC-mismatched kidney allografts in rhesus monkeys treated with posttransplant rabbit antithymocyte globulin (RATG)* and donor-specific bone marrow (DBM). Here we have investigated the effect of adjunctive immunosuppressive drugs on induction of allogeneic unresponsiveness in this primate model. Parameters examined included median kidney allograft survival time (MST), development of specific antidonor T lymphocyte-mediated cytotoxicity (LMC) and antidonor antibody-dependent cellular cytotoxicity (ADCC). Posttransplant infusion of DBM in RATG-treated kidney allograft recipients resulted in 70 days MST and a dramatic reduction in the incidence of antidonor LMC. However, development of antidonor ADCC was similar to that of RATG controls, suggesting an immune deviation or split tolerance in these animals. Adjunctive azathioprine did not have a beneficial effect in recipients given RATG & DBM, resulting in decreased MST and increased antidonor LMC responses. In contrast, adjunctive cyclosporine (CsA) and low-dose prednisone (P) exerted an additive immunosuppressive effect resulting in a 50% increase in MST and no detectable antidonor LMC. However, CsA & P appeared to enhance the humoral alloimmune response, increasing the incidence of recipients with antidonor ADCC. Long-term graft survival in this group was limited by chronic rejection and especially by CsA-associated toxicity. These studies point out deterrents and also directions for optimizing adjunctive immunosuppression in primates treated with posttransplant RATG & DBM. The results with CsA are relatively encouraging. However, the prevalence of alloantibody and of chronic rejection in these animals suggests that more homogeneous success with tolerance induction in this model may require adjunctive immunosuppressive strategies that reduce humoral immunity.

Adjuvants, Immunologic↗
PubMed1989

A nonsense mutation in the apolipoprotein C-IIPadova gene in a patient with apolipoprotein C-II deficiency.

The apo C-II gene from a patient with apo C-II deficiency has been sequenced after amplification by the polymerase chain reaction. A substitution of an adenosine for a guanosine at position 3002 in exon 3 of the patient's gene was identified by sequence analysis. This mutation leads to the introduction of a premature termination codon (TAA) at a position corresponding to amino acid 37 of mature apo C-II and to the formation of a new Rsa I restriction enzyme site not present in the normal apo C-II gene. Amplification of DNA from family members by the polymerase chain reaction and digestion with Rsa I established that the patient is a true homozygote for the mutation. Analysis of the patient's plasma by two-dimensional gel electrophoresis and immunoblotting detected an apo C-II that exhibited abnormal electrophoretic mobility. We propose that the C to A substitution in the apo C-IIPadova gene is the primary genetic defect that leads to premature termination and the synthesis of a truncated 36 amino acid apo C-II that is unable to activate lipoprotein lipase.

Adenosine↗
PubMed1989

Limited small cell lung cancer: possible prognostic impact of initial chemotherapy doses.

While the effect of chemotherapy dose on tumor response in small cell lung cancer has been fairly well established, the effect on survival has been retrospectively analyzed only in some series. This particular point was studied in a series of 52 consecutive patients with limited small cell lung cancer treated by an alternating radiotherapy-chemotherapy schedule. The induction treatment consisted of 6 chemotherapy cycles (the planned doses were: doxorubicin 40 mg/m2 day 1, VP16213 75 mg/m2 days 1-3, cyclophosphamide 300 mg/m2 days 3-6, and cisplatinum 100 mg/m2 day 2) alternated after the first 2 cycles with 3 courses of thoracic radiotherapy delivering a total dose of 55 Gy. Eighty-one percent of patients went into complete remission and the 3-year relapse-free survival was 24%. A multivariate analysis of prognostic factors took into account age, sex, T stage, performance status, delayed hematological toxicity to the first course of chemotherapy, actual dose/m2 of each drug during the first course and mean dose/course delivered during the induction treatment after the first cycle of chemotherapy. It was possible to identify 3 independent factors influencing overall survival and relapse-free survival: actual initial dose of cisplatinum, actual initial dose of cyclophosphamide and the T stage. The effect of the initial dose of cisplatinum and cyclophosphamide proved to be linear on relapse-free survival. The results of this analysis show a possible effect of initial doses of chemotherapy in the management of limited small cell lung cancer in terms of both distant metastasis and overall survival rates.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Expression of the rpl23, rpl2 and rps19 genes in spinach chloroplasts.

The expression of the spinach rpl23, rpl2 and rps19 chloroplast genes has been studied. The rpl23 gene identified in tobacco and Marchantia, is split into two overlapping reading frames in spinach. S1 mapping has shown that initiation sites could occur upstream of each reading frames. A large transcription unit is also present covering the rpl2 and rps19 genes. The rps19 and rpl2 gene products are identified by NH2-terminal amino acid sequences. They correspond to spinach chloroplast ribosomal proteins CS-S23 and CS-L4, respectively. No product of the rpl23 gene was detected in the chloroplast 50S ribosomal subunit. This strongly suggest that a corresponding gene has been transfered into the nucleus.

Amino Acid Sequence↗
PubMed1988

Radical radiotherapy alone in non-operable breast cancer: the major impact of tumor size and histological grade on prognosis.

This retrospective study involved 319 non-operable breast cancer patients treated by radiotherapy alone with doses of 65 Gy at the Institut Gustave-Roussy (IGR). These patients either had operable tumors but were unfit for general anesthesia or had inoperable tumors due to local contraindications. Most of them had advanced tumors: 21% less than 7 cm; 30% N2 or N3; 30% with inflammatory carcinomas. The 5- and 10-year survival was 40 and 19%, respectively. The local and distant relapse-free rate was 56 and 33% at 5 years and 44 and 28% at 10 years respectively. Results were analyzed according to tumor size, clinical node involvement, histologic grade, age, skin invasion and tumor dose. A multivariate analysis demonstrated that tumor size (p = 10(-3)) and histological grade (HG) (p = 10(-2)) were both significant factors predicting local relapse. Histological grade (p = 10(-3)), tumor size (p = 10(-2)) and clinical node involvement (p = 10(-2)) were the most significant factors predicting distant relapses. An individual risk (IR) of local recurrence and of distant recurrence was defined according to the above factors and was demonstrated to be good prognostic index. Tumor doses above 80 Gy did not increase local control. We recommend the general use of histological grading as it seems important for prediction of local and distant control in patients treated by radiotherapy alone.

Actuarial Analysis↗
PubMed1988

Thoracic CT-scanning follow-up of residual mediastinal masses after treatment of Hodgkin's disease.

Sequential thoracic CT-scanning was performed for 14 patients presenting with residual mediastinal masses on chest X-ray after treatment of stage I and II Hodgkin's disease (HD). Eleven patients initially presented with bulky mediastinal involvement. No mediastinal biopsy was performed. No local recurrence was detected at a 48 month median follow-up. Early evaluation by CT-scanning showed cystic degeneration in three cases. Sequential CT-scans on longer follow-up demonstrated continuous regression of residual masses in six cases and no or limited volume reduction in six other cases. In two patients, part of the residual mass remained stable and the other part showed reduction in size. In addition, late calcifications developed in four cases. The results of sequential CT-scanning suggest that residual mediastinal masses do not generally represent active disease. Hence additional, potentially toxic, therapy can be avoided.

Follow-Up Studies↗
PubMed1988

Use of enzyme immunoassay for the rapid diagnosis of Chlamydia trachomatis endocervical infection in female adolescents.

Enzyme immunoassay (EIA) has been proposed as an alternative to tissue culture for the detection of Chlamydia trachomatis in cervical specimens. The diagnostic efficacy of EIA was compared to tissue culture in 113 teenaged females attending an adolescent reproductive health program. Infection was diagnosed by tissue culture in 16% of subjects. Compared with tissue culture, EIA demonstrated a sensitivity of 100%, specificity of 88%, positive predictive value of 62%, and a negative predictive value of 100%. These data indicate that EIA is an acceptable alternative to tissue culture when screening for C. trachomatis endocervical infection in adolescent females.

Adolescent↗
PubMed1988

Radiotherapy alone for oropharyngeal carcinomas: the role of fraction size (2 Gy vs 2.5 Gy) on local control and early and late complications.

This retrospective study involved 150 patients treated for oropharyngeal carcinoma by external radiotherapy alone at the Institut Gustave-Roussy. The midplane tumor dose was 70 Gy delivered in 7 weeks. During 1981, 63 patients were treated with 5 fractions (5 F) of 2 Gy per week. The following year, 87 patients, were treated with 4 fractions (4 F) of 2.5 Gy per week. Prognostic factors were equally distributed in both groups. The locoregional tumor control was 83% for the 4 F patients and 83% for the 5 F patients. Degree and incidence of acute reactions with both fractionation regimens were similar. Necrosis of the oropharyngeal mucosa and trismus were significantly more severe and more frequent in the 4 F group (23% and 20% respectively) than in the 5 F group (10% and 5% respectively) (p = 0.03 and p = 0.01). Other late effects such as skin necrosis (6% in the 4 F group versus 0% in the 5 F group) and severe cervical sclerosis (12 vs 5%) were also more frequent in the 4 F group than in the 5 F group but the difference was not significant. The results suggest a greater sensitivity of late compared to early normal tissue effects and of tumor response to an increase in dose per fraction (from 2 Gy to 2.5 Gy) in oropharyngeal carcinoma.

Female↗
PubMed1988

The economic impact of DRG payment policies on air-evacuated trauma patients.

This study assessed the injury severity, patient outcome, the cost of care, and the economic impact of Medicare DRG payment policies on patients referred to a Level I trauma center. Only 11 of 283 admitted traumatized patients were Medicare patients. Yet, these 11 Medicare patients left the trauma center with a deficit of $249,601. No significant differences were found between the Medicare and non-Medicare groups for Trauma Score, CRAMS Score, Glasgow Coma Score, Injury Severity Score, ICU or hospital length of stay, disability, or mortality. Under DRG's, Medicare payments ($4,237 +/- 2,351/patient) have fallen to 20% of prior cost-based Medicare reimbursements ($21,542 +/- 34,170/patient), are providing only 16% of hospital costs ($26,928 +/- 42,713/patient), and are significantly (p less than 0.0001) less than non-Medicare reimbursements ($15,288 +/- 17,111/patient). Despite the high financial losses occurring when the trauma center treats referred traumatized Medicare patients, when all referred Medicare and non-Medicare patient trauma reimbursements are combined, overall trauma revenues have declined by only 4.3% under DRG's. If Medicare DRG payments were to be adopted by all third-party payers, reimbursement ($5,058 +/- 4,090/patient) would be significantly (p less than 0.0001) less than current hospital reimbursements ($14,801 +/- 16,537/patient) and costs ($16,121 +/- 17,624/patient). These results indicate that although high financial losses result when caring for traumatized Medicare patients, DRG's have not had a major financial effect upon centers receiving referred trauma patients because of the low numbers of admitted traumatized Medicare patients. However, if third-party payers were to enact the Medicare payment system, devastating economic losses would be inflicted upon major trauma centers.

Adult↗
PubMed1988

Effectiveness of implementing a trauma triage system on outcome: a prospective evaluation.

A 9-month prospective study was conducted in Salt Lake County to evaluate the efficacy of a field trauma triage system using the CRAMS score. Before the triage system was implemented trauma victims were taken to the nearest appropriate hospital. Post-implementation, trauma victims with field CRAMS scores of 1 through 6 were triaged to the Level I Trauma Center. Of the 113 study patients, 53 were in the pre-implementation phase and 60 in the post-implementation phase. The study patients with CRAMS scores of 4 or less had lower mortality when cared for at the Level I Trauma Center (p = 0.013). We conclude that trauma patients who are severely injured (CRAMS less than or equal to 4) have a significantly higher rate of survival if taken to the Level I Trauma Center. The use of the CRAMS triage system appears to be an effective approach toward improving trauma care in Salt Lake County.

Adult↗
PubMed1988

Diagnosis of pancreatic allograft rejection by measurement of urinary radioimmunoreactive insulin.

The accurate, early, and sensitive diagnosis of pancreatic allograft rejection is one of the major problems in clinical pancreas transplantation today. Pancreaticocystotomy is a popular technique for pancreas transplantation that permits simple and frequent urinary chemistry examinations. In this experiment, 20 mongrel dogs with a bladder-drained pancreatic transplant had serial monitoring of urinary amylase (UA) and urinary insulin (UI). The mean UI in the nonrejection state was 9.6 +/- 12 mIU/L. In eight dogs varying degrees of rejection were documented by histopathology. All three animals having severe acute rejection had high levels of IU (all greater than 300-800 mIU/L). Of the five animals with mild-to-moderate rejection, all had significant UI elevations to greater than 100 mIU/L but none had elevations above 200 mIU/L (P less than 0.05 for all groups). Ten animals were treated with prednisone, Imuran, and cyclosporine (CsA), and five of these dogs had good graft function for greater than 14 days, during which the mean UI was extremely low (11 +/- 6.4 mIU/L, P less than 0.05). These values were not significantly different from the 0-14-day values for three pancreas autotransplants with bladder drainage (8.9 +/- 7.2 mIU/L, P less than 0.05). All rejections were preceded by significant rises of UI occurring two to five days prior to rejection. In seven animals, early graft dysfunction (1-4 days) developed, with total graft necrosis by five days. This graft injury was presumably caused by preservation damage or early vascular thrombosis and was associated with early (1-4 days) marked elevations of the UI (greater than 300 mIU/L). None of the animals with grafts surviving to rejection at seven days or more had these early severe elevations, and thus these early UI rises are pathognomonic of graft damage. In contrast, UA and lipase showed inconsistent association with rejection or early damage, although falls in UA generally occurred at or following the time of rejection. Marked daily variations in UA measurements were the most difficult aspect of UA monitoring. Serial electromagnetic flow probe studies of blood flow to the pancreas graft showed a good correlation between loss of blood flow and rises in UI associated with early graft injury. These results suggested that the UI assay gives a sensitive, early, accurate, and specific differential prediction of pancreas graft dysfunction. Specifically, the UI assay appears to be of value not only in the early differential diagnosis of graft injury and graft rejection, but also in the assessment of the severity of rejection.(ABSTRACT TRUNCATED AT 400 WORDS)

Amylases↗