PubMed Health⌕ Search

Biomedical subjects

C Riggs

Publications and source records attributed to C Riggs.

At least 19 recordsLinked to original sources
PubMed2001

Role of common gene variations in the molecular pathogenesis of short-chain acyl-CoA dehydrogenase deficiency.

ABSTRACT Short-chain acyl-CoA dehydrogenase (SCAD) deficiency is considered a rare inherited mitochondrial fatty acid oxidation disorder. Less than 10 patients have been reported, diagnosed on the basis of ethylmalonic aciduria and low SCAD activity in cultured fibroblast. However, mild ethylmalonic aciduria, a biochemical marker of functional SCAD deficiency in vivo, is a common finding in patients suspected of having metabolic disorders. Based on previous observations, we have proposed that ethylmalonic aciduria in a small proportion of cases is caused by pathogenic SCAD gene mutations, and SCAD deficiency can be demonstrated in fibroblasts. Another - much more frequent - group of patients with mild ethylmalonic aciduria has functional SCAD deficiency due to the presence of susceptibility SCAD gene variations, i.e. 625G>A and 511C>T, in whom a variable or moderately reduced SCAD activity in fibroblasts may still be clinically relevant. To substantiate this notion we performed sequence analysis of the SCAD gene in 10 patients with ethylmalonic aciduria and diagnosed with SCAD deficiency in fibroblasts. Surprisingly, only one of the 10 patients carried pathogenic mutations in both alleles, while five were double heterozygotes for a pathogenic mutation in one allele and the 625G>A susceptibility variation in the other. The remaining four patients carried only either the 511C>T or the 625G>A variations in each allele. Our findings document that patients carrying these SCAD gene variations may develop clinically relevant SCAD deficiency, and that patients with even mild ethylmalonic aciduria should be tested for these variations.

Acyl-CoA Dehydrogenase↗
PubMed1997

Continuous infusion, intravesical doxorubicin for the treatment of regionally advanced bladder cancer: a phase I-II trial.

Patients with regionally advanced bladder cancer not considered candidates for definitive surgical intervention underwent continuous antegrade infusion of doxorubicin by percutaneous nephrostomy tube. Doxorubicin was administered for 7 consecutive days at a rate designed to achieve target urinary concentrations (range 5-80 micrograms/ml). Urine and serum concentrations of doxorubicin were monitored daily. Toxicity was assessed by serial renal scans, antegrade nephrostograms, blood counts, and serum chemistries. Patients were restaged after three cycles of therapy. In all, 23 cycles, constituting 156 days of therapy, were administered to 10 patients. Target urinary drug levels were achieved during all cycles. Total doxorubicin dose ranged from 125 to 2,500 mg. No systemic (neutropenia or myocardial dysfunction) or regional toxicity (extravasation, sepsis, stricture) was noted. Five of 10 patients tolerated the planned three treatment cycles. Poor performance status (PS, Eastern Cooperative Oncology Group: ECOG 3) strongly correlated with treatment intolerance and early death from disease. After three cycles of therapy, 2 of 5 evaluable patients had stable disease, I had radiographic partial response (PR) with a biopsy demonstrating extensive tumor necrosis, I had no identifiable tumor at the time of restaging transurethral resection of bladder tumor (TURBT), and a final patient with upper and lower tract carcinoma in situ (CIS) was cytologically staged NED. (no evidence of disease). These findings demonstrate the feasibility and low toxicity of this approach.

Administration, Intravesical↗
PubMed1995

Gastric dilatation-volvulus after splenic torsion in two dogs.

Two dogs developed gastric dilatation-volvulus 2 and 17 months, respectively, after splenectomy for treatment of splenic torsion. Splenic displacement and torsion may stretch the gastric ligaments, allowing increased mobility of the stomach. After splenectomy, an anatomic void may be created in the cranioventral part of the abdomen, contributing to the mobility of the stomach. Veterinarians treating dogs with isolated splenic torsion may wish to consider prophylactic gastropexy at splenectomy, to reduce the chance of future gastric dilatation-volvulus. Prophylactic gastropexy should be done only if the dog's hemodynamic status is stable enough to allow for performance of the additional surgery.

Animals↗
PubMed1990

Intraocular silicone prostheses in a dog and a horse with corneal lacerations.

Intraocular silicone prostheses were implanted in the eyes of a horse and a dog with traumatic corneal lacerations and protrusion of intraocular contents. Several months after surgery, the horse and dog were tolerating the intraocular prostheses, and the appearance was cosmetically acceptable. This contradicts earlier reports that have cited corneal disease as a contraindication for implantation of intraocular silicone prostheses.

Animals↗
PubMed1990

Effect of histocompatibility factors on pulmonary retention of indium-111-labeled granulocytes.

Granulocyte transfusions are associated with a number of side effects including febrile transfusion reactions and occasionally pulmonary infiltrates. There is evidence that the presence of preformed antibodies may be a cause of these complications. In this study, allogeneic 111Indium-labeled granulocytes were used to evaluate the pulmonary retention of radioactivity in alloimmunized and non-alloimmunized patients in an attempt to assess antibody effect on granulocyte migration. After injection of labeled allogeneic granulocytes into neutropenic patients, the ratios of lung to heart activity were calculated for the first 30 min of scanning. There was significantly greater retention of radioactivity from cells in the lungs of patients who were alloimmunized, having both lymphocytotoxic (anti-HLA) and leuko-agglutinating antibodies, compared to the activity in the lungs of non-alloimmunized patients (P less than .001) or of patients receiving autologous granulocytes (P less than .001). This study demonstrates that labeled, mismatched granulocytes may be retained in the lungs for a significantly longer time in patients with preformed antibodies. This implies that transfusion of large numbers of such mismatched granulocytes, i.e., granulocyte transfusions, may also be retained in the lungs of alloimmunized patients, which could lead to pulmonary compromise. Therefore, granulocyte transfusions from random donors should not be given to alloimmunized patients.

Blood Transfusion↗
PubMed1990

Adjunctive therapy (whole body hyperthermia versus lonidamine) to total body irradiation for the treatment of favorable B-cell neoplasms: a report of two pilot clinical trials and laboratory investigations.

Based on earlier clinical and preclinical investigations, we designed two different pilot trials for patients with nodular lymphoma or chronic lymphocytic leukemia. These studies evaluated the use of either 41.8 degrees C whole body hyperthermia (WBH), or the nonmyelosuppressive chemotherapeutic drug, lonidamine (LON), as an adjunct to total body irradiation (TBI) (12.5 cGy twice a week, every other week for a planned total dose of 150 cGy). Whole body hyperthermia was initiated approximately 10 min after total body irradiation; lonidamine was administered orally (420 mg/m2) on a daily basis. Although entry to the studies was nonrandomized, the two patient populations were accrued during the same time frame and were comparable in terms of histology, stage of disease, performance status, and prior therapy. Of 8 patients entered on the TBI/WBH study, we observed 3 complete responses (CR), 4 partial responses (PR), and 1 improvement (i.e., a 48% decrease in tumor burden). Of 10 patients entered in the TBI/LON study, there was 1 CR and 4 PR. For the TBI/WBH study, myelosuppression was not treatment-limiting; there were no instances of infection or bleeding and platelet support was never required. The median survival time for the TBI/WBH study is 52.5 months based on Kaplan Meir estimates. Two patients remain in a CR. The median time to treatment failure (MTTF) is 9.4 months (90% confidence interval = 7-15.4 months). In the TBI/LON study, 50% of patients receiving TBI required treatment modification due to platelet-count depression during therapy, but there were no instances of infection or bleeding. Frequently observed LON-related toxicities included myalgias, testicular pain, photophobia and ototoxicity. For the TBI/LON study, median survival is 7.6 months; MTTF was 2.4 months. In analyzing the results of these pilot studies, our subjective clinical impressions lead to the hypothesis that WBH protected against TBI-induced thrombocytopenia during therapy, whereas LON had no effect on TBI-induced myelosuppression. This speculation was tested and confirmed in a series of in vitro and in vivo experiments.

Adult↗
PubMed1988

Phase I trial of lonidamine with whole body hyperthermia in advanced cancer.

Lonidamine is a dechlorinated derivative of indazole-3-carboxylic acid which preclinically synergizes with hyperthermia. Clinically, this nonmyelosuppressive drug (given p.o. daily) is active as a single agent in a variety of malignancies. On this basis, a Phase I study which incorporates a drug escalation schema as well as an escalation in temperature, i.e., 41.0 degrees C for 85 min to 41.8 degrees C for 75 min, was executed. Induction therapy included seven whole-body hyperthermia treatments. Whole-body hyperthermia was delivered using a radiant heat system. Twenty-four patients were entered on study. Of these, 20 were evaluable for response. Group A (60 mg/m2) had three patients with three no responses. Group B (180 mg/m2) consisted of three patients: one lymphoma, partial response; two gastrointestinal adenocarcinomas, one partial response and one improvement, i.e., less than a partial response. Group C (360 mg/m2) had 17 patients: two lung cancers, one complete response and one improvement; one melanoma, improvement; one ovarian, disease stabilization (greater than 100 days); two adenocarcinomas of the gastrointestinal tract, two disease stabilizations; 11 patients, no responses; one patient entered at this level was ineligible for study and did not receive lonidamine. Therapy was well tolerated. Of 16 patients reporting myalgias, two required a lonidamine dose reduction; one patient required dose reduction for central nervous system toxicity. Results obtained encourage Phase II clinical trials.

Adult↗
PubMed1988

Rapid development of hepatocellular neoplasms in aging male C3H/HeNCr mice given phenobarbital.

One hundred and nineteen male C3H/HeNCr mice, 12 months of age, with spontaneous preneoplastic and neoplastic hepatocellular lesions were given phenobarbital (PB) at 500 ppm in drinking water. Groups of 9-10 mice were sacrificed after 12, 24 and 36 weeks of PB exposure. Identical numbers of untreated controls were used. A group of 6-week-old C3H/HeNCr mice were also given PB and sacrificed at 12, 24 or 36 weeks. In aging mice, PB exposure significantly increased the number of gross tumors or microscopic foci, adenomas or carcinomas per liver at all time periods, especially unique eosinophilic proliferative lesions, while young mice did not develop any focal proliferative lesions by 36 weeks. These findings suggest that in aging mice a fraction of the hepatocyte population (normal, spontaneously-initiated or preneoplastic) is more highly susceptible to phenobarbital 'carcinogenesis' than are hepatocytes of younger mice.

Age Factors↗
PubMed1987

Phase 2 trial of streptozotocin by continuous infusion for metastatic colorectal carcinoma.

Streptozotocin is a nitrosourea with minimal activity against colorectal carcinoma when given by bolus administration. Continuous infusion (CI) streptozotocin has been reportedly less toxic. Twenty-six patients with widely advanced colorectal carcinoma (most heavily pretreated) received 1-3 courses of Streptozotocin by CI to determine efficacy. Two patients (8%) had an objective response. Although CI Streptozotocin is less toxic, it does not have substantial efficacy in colorectal cancer in previously treated patients with widespread metastases.

Adult↗
PubMed1986

Therapy of autochthonous skin cancers in mice with intravenously injected liposomes containing muramyltripeptide.

Liposomes containing the immunomodulator muramyltripeptide phosphatidylethanolamine (MTP-PE) or free saline were injected i.v. into BALB/c mice with autochthonous skin cancers induced by chronic exposure to ultraviolet irradiation. Treatment with liposomes containing MTP-PE produced significant retardation in the growth of the primary autochthonous skin cancers and significantly prolonged survival of the treated mice as compared with the saline-treated controls. Since ultraviolet-irradiated mice have a defect in immunological recognition of their autochthonous tumors, the therapeutic effects of liposomes containing MTP-PE are very encouraging. These results suggest that liposomes containing MTP-PE could be used for the treatment of patients with skin cancer or other malignant diseases.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1985

Clinical oncology assistantship program for medical students.

The Clinical Oncology Assistantship Program has been offered to approximately 16 sophomore medical students each year at the University of Arkansas for Medical Sciences since 1975. This is an elective, 10-week program given during the summer recess. In the first week of the program, core lectures are given by a multidisciplinary team of cancer educators affiliated with the University of Arkansas. Following this, students spend nine weeks rotating through medical, surgical, and pediatric oncology services of the University of Arkansas for Medical Sciences. In addition, they spend several hours during the program participating in self-directed learning activities at the university's Cancer Teaching Center. The program has been well received by the students, and each year all of the available positions have been filled. Responses on a follow-up questionnaire sent in July 1983 to past participants showed that they continued to rate the program highly. Moreover, 78 percent of the respondents felt the program had influenced positively their attitude toward cancer patients.

Arkansas↗
PubMed1984

Di(2-ethylhexyl)phthalate but not phenobarbital promotes N-nitrosodiethylamine-initiated hepatocellular proliferative lesions after short-term exposure in male B6C3F1 mice.

The differential effects of short- or long-term exposure to the liver tumor promoters di(2-ethylhexyl)phthalate (DEHP) or phenobarbital (PB) were studied in male B6C3F1 mice. Mice were injected intraperitoneally (i.p.) at 4 weeks of age with N-nitrosodiethylamine (DEN) at a dosage of 80 mg/kg. At 5 weeks of age, the mice were fed diets containing PB or DEHP for periods of from 1 to 168 days and killed at 168 or 252 days. When DEHP was fed at a dietary level of 3000 ppm for 28, 84, or 168 days, or PB was fed in the water at 500 ppm for 168 days, there were significantly increased incidences of mice with focal hepatocellular proliferative lesions (FHPL) as compared with those in mice receiving DEN alone. There was no significant promotion of FHPL when DEHP was fed for 1 or 7 days or when PB was fed for 1, 7, 28, or 84 days. Thus, DEHP was an effective promoter after only 28, 84, or 168 days exposure whereas PB required 168 days of continuous exposure for a promotive effect to be evident.

Animals↗
PubMed1983

Dissimilar patterns of promotion by di(2-ethylhexyl)phthalate and phenobarbital of hepatocellular neoplasia initiated by diethylnitrosamine in B6C3F1 mice.

Potentially preneoplastic hepatocellular hyperplastic foci and hepatocellular neoplasms were studied in weanling male B6C3F1 mice that received a single i.p. injection (80 mg/kg) of diethylnitrosamine (DEN) at 4 weeks of age, followed by oral administration of phenobarbital (PB) or di(2-ethylhexyl)-phthalate (DEHP) that began 2 weeks after DEN injection and continued for up to 6 months. PB was administered in drinking water at 500 p.p.m. and DEHP in the feed at 3000, 6000 or 12 000 p.p.m. Groups of mice were sacrificed at 2, 4 and 6 months after DEN exposure; formalin-fixed liver samples were evaluated histologically. Hepatocellular neoplasms and foci of hyperplasia were quantified with the aid of an image analysis computer. Few foci were seen at 2, 4 or 6 months in mice exposed to DEN, PB or DEHP alone, while numerous foci and neoplasms were seen in mice given DEHP or PB after DEN. Area-perimeter measurements for each hepatocellular focus or neoplasm transection revealed that foci and neoplasms in PB-exposed mice increased both in size (area and volume) and in number throughout the study. In DEHP-exposed mice the pattern of response was different in that the numbers of foci did not increase between 4 and 6 months, but the foci increased in mean diameter and volume throughout the experiment. Foci and tumors appeared earlier in mice given higher dietary levels of DEHP than in those given lower doses. By the end of the study the number of foci per unit volume of liver was similar in mice given any dose of DEHP, but their volume was dose-related. Hepatocellular foci and neoplasms in PB-exposed mice were composed predominantly of eosinophilic hepatocytes, while in DEHP-exposed mice, basophilic foci and neoplasms predominated; the latter were more malignant in appearance than neoplasms in PB-exposed mice. At 6 months, the neoplasms in high dose DEHP-exposed mice were significantly larger than those in PB exposed mice. Histochemistry, however, revealed similarities between lesions in mice exposed to PB or DEHP. PB given continuously for 6 months revealed no initiating activity of DEHP given once by gavage and followed by PB in drinking water. Both morphology and biology of hepatocellular foci and neoplasms, which develop in mice after a single exposure to a carcinogen with initiating activity, thus depend, in part, on the subsequent promoting agent. More than one process of tumor promotion, as characterized by a specific sequence of morphologic and biochemical changes, is possible for the mouse hepatocyte.

Adenoma↗