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Biomedical subjects

T Graves

Publications and source records attributed to T Graves.

At least 19 recordsLinked to original sources
PubMed2001

Surveying Saccharomyces genomes to identify functional elements by comparative DNA sequence analysis.

Comparative sequence analysis has facilitated the discovery of protein coding genes and important functional sequences within proteins, but has been less useful for identifying functional sequence elements in nonprotein-coding DNA because the relatively rapid rate of change of nonprotein-coding sequences and the relative simplicity of non-coding regulatory sequence elements necessitates the comparison of sequences of relatively closely related species. We tested the use of comparative DNA sequence analysis to aid identification of promoter regulatory elements, nonprotein-coding RNA genes, and small protein-coding genes by surveying random DNA sequences of several Saccharomyces yeast species, with the goal of learning which species are best suited for comparisons with S. cerevisiae. We also determined the DNA sequence of a few specific promoters and RNA genes of several Saccharomyces species to determine the degree of conservation of known functional elements within the genome. Our results lead us to conclude that comparative DNA sequence analysis will enable identification of functionally conserved elements within the yeast genome, and suggest a path for obtaining this information.

Base Sequence↗
PubMed1999

Effect of aspirin and ifetroban on skeletal muscle blood flow in patients with congestive heart failure treated with Enalapril. Ifetroban Study Group.

OBJECTIVES: The purpose of this study was to determine the acute and chronic effects of cyclooxygenase inhibition with aspirin and thromboxane A2 receptor blockade with ifetroban on the chronic vasodilating effects of enalapril in the skeletal muscle circulation of patients with heart failure. BACKGROUND: Angiotensin-converting enzyme inhibition and antiplatelet therapy with aspirin independently reduce the risk for subsequent nonfatal coronary events in survivors of myocardial infarction. The safety of the combined administration of angiotensin-converting enzyme inhibitors and aspirin has been questioned due to their divergent effects on the vascular synthesis of vasodilating prostaglandins. METHODS: Forearm blood flow (ml/min/100 ml) at rest and during rhythmic handgrip exercise and after transient arterial occlusion was determined by strain gauge plethysmography before and 4 h and six weeks after combined administration of enalapril with either aspirin, ifetroban or placebo in a multicenter, double-blind, randomized trial of 62 patients with mild to moderate heart failure. RESULTS: Before randomization, forearm hemodynamics were similar in the three treatment groups except for increased resting forearm blood flow and decreased resting forearm vascular resistance in the aspirin group when compared with the placebo group. After combined administration of enalapril and study drug for 4 h and six weeks, changes from prerandomization values of mean arterial pressure, forearm blood flow and forearm vascular resistance at rest, during handgrip exercise and after transient arterial occlusion did not differ among the three treatment groups. CONCLUSIONS: These findings demonstrate that the vasodilating effects of enalapril in the skeletal muscle circulation of patients with heart failure are not critically dependent on prostaglandin pathways.

Aged↗
PubMed1999

Office-based surgery and cost avoidance in an obstetrics and gynecology residency program.

AUDIENCE: This article is designed both for graduate medical educators and financial officers of teaching hospitals. GOAL: To present the financial and clinical implications of a resident-run, attending-supervised office-based surgery center. OBJECTIVES: 1. Describe the recent changes in volume of patients available for resident education in obstetrics and gynecology. 2. Describe the accounting method of calculating the cost of office versus hospital outpatient procedures. 3. Describe the financial and educational benefits of an office-based surgery program run by residents with the supervision of attending physicians.

Ambulatory Surgical Procedures↗
PubMed1998

Precise mapping and characterization of the RNA primers of DNA replication for a yeast hypersuppressive petite by in vitro capping with guanylyltransferase.

The active origins of DNA replication for yeast (Saccharomyces cerevisiae) mitochondrial DNA share 280 conserved base pairs and have a promoter. Since intact replication intermediates retain their initiating ribonucleotide triphosphate, we used guanylyltransferase to in vitro cap the replication intermediates present in restriction enzyme-cut DNA from an ori-5 hypersuppressive petite. Restriction mapping and RNA sequencing of these labeled intermediates showed that each DNA strand is primed at a single discrete nucleotide, that one primer starts at the promoter and that the other primer starts 34 nt away, outside the conserved region. Deoxyribonuclease digestion of the capped fragments left resistant RNA primers, which enabled identification of zones of transition from RNA to DNA synthesis. Some of the results contradict the prevailing model for priming at the yeast mitochondrial origins.

Base Sequence↗
PubMed1998

First reported case of hantavirus pulmonary syndrome in Oklahoma.

Hantavirus Pulmonary Syndrome (HPS) is a condition of rapidly progressive pulmonary failure with a case-fatality rate of almost 50 percent. Rodents serve as the reservoir for hantaviruses and human infection occurs primarily via aerosolized virus in rodent excreta. The rodent reservoir for the disease is widespread across Oklahoma and the first case of HPS has recently been confirmed in an Oklahoma resident. Physicians should suspect HPS in a previously healthy person who develops a febrile illness and respiratory insufficiency and has potentially been exposed to the virus. Common laboratory findings include a left-shifted neutrophilic leukocytosis, elevated hematocrit and thrombocytopenia. Therapy is supportive. If HPS is suspected, the patient should be immediately transferred to a facility that can provide aggressive supportive care.

Adult↗
PubMed1997

Adverse events after discontinuing medications in elderly outpatients.

BACKGROUND: Discontinuation of drug therapy is an important intervention in elderly outpatients receiving multiple medications, but it may be associated with adverse drug withdrawal events (ADWEs). OBJECTIVE: To determine the frequency, types, timing, severity, and factors associated with ADWEs after discontinuing medications in elderly outpatients. PATIENTS: One hundred twenty-four ambulatory elderly participants in 1-year health service intervention trial at the Durham Veterans Affairs General Medicine Clinic in Durham, NC, who stopped taking medications. METHODS: A geriatrician retrospectively reviewed computerized medication records and clinical charts to determine medications no longer being taken and adverse events in the subsequent 4-month period. Possible ADWEs, determined by using the Naranjo causality algorithm, were categorized by therapeutic class, organ system, and severity. RESULTS: Of 238 drugs stopped, 62 (26%) resulted in 72 ADWEs among 38 patients. Cardiovascular (42%) and central nervous system (18%) drug classes were most frequently associated with ADWEs. The ADWEs most commonly involved the circulatory (51%) and central nervous (13%) systems, and 88% were attributed to exacerbations of underlying disease. Twenty-six ADWEs (36%) resulted in hospitalization or an emergency department or urgent care clinic visit. Only the number of medications stopped was associated with ADWE occurrence (adjusted odds ratio, 1.89; 95% confidence interval, 1.33-2.67). CONCLUSIONS: Most medications can be stopped in elderly outpatients without an ADWE occurrence. However, when ADWEs occur they resulted in substantial health care utilization. Practitioners should strive to discontinue drug therapy in the elderly but be vigilant for disease recurrence.

Acute Disease↗
PubMed1996

Case report: locally acquired trichinosis in an immigrant from Southeast Asia.

The authors report a case of trichinosis acquired in Oklahoma City by an immigrant from Southeast Asia. The 49-year-old female reported having abdominal discomfort, nausea, and vomiting, and had purchased and eaten lightly cooked pork. She also complained of fatigue, anorexia, and muscle aches for several months. An immigrant from Laos, she stated that she regularly eats pork and prefers it rare or mildly cooked. The authors caution local physicians to be aware of the increased risk of trichinosis among Southeast Asian immigrants in the area, particularly those from Laos and Cambodia. Continued emphasis on the need to thoroughly cook all pork products is necessary if the incidence of trichinosis in the U.S. is to be controlled.

Animals↗
PubMed1992

Emesis as a complication of cancer chemotherapy: pathophysiology, importance, and treatment.

Up to 30% of patients receiving chemotherapy experience uncontrolled nausea and vomiting despite pharmacotherapeutic advances. Currently marketed agents used to treat these symptoms are compared. Dose escalation of these agents may improve response rates. Recent focus has been on a new class of antiemetics, the serotonin antagonists. Ondansetron, currently the only serotonin antagonist with Food and Drug Administration approval for treatment of chemotherapy-induced emesis, demonstrates the efficacy and potential advantages of this class of antiemetics.

Antiemetics↗
PubMed1991

HIV seroprevalence in Oklahoma childbearing women.

From October 1989 through September 1990, we conducted an unlinked seroprevalence survey in Oklahoma to determine the prevalence of human immunodeficiency virus, type 1 (HIV) in women at the time of childbirth. Blood specimens obtained from 41,809 newborns in conjunction with the state's newborn metabolic screening program were tested for HIV after personal identifiers were removed. The overall HIV seroprevalence rate was 0.02% (10/41,809). Rates were highest for mothers aged 30 to 39 years (0.06%, 3/5,158). No difference was found between the HIV seroprevalence rates for women residing in standard metropolitan areas (MSAs) of the state (0.03%, 6/21,105) and women residing in non-metropolitan areas (0.03%, 3/11,904). When compared to other states where surveys have been done, Oklahoma's rate of HIV infection in childbearing women was low.

Adult↗
PubMed1990

Early postoperative intraperitoneal chemotherapy as an adjuvant therapy to surgery for peritoneal carcinomatosis from gastrointestinal cancer: pharmacological studies.

Gastrointestinal malignancy may spread to peritoneal surfaces in the absence of lymphatic or hematogenous metastases. To treat peritoneal carcinomatosis, a uniformly lethal disease process, extensive cytoreductive surgery and i.p. chemotherapy were combined. Early postoperative i.p. chemotherapy was instilled in the first few days after the surgical procedure in an attempt to treat anatomic sites that would be sealed off by postoperative adhesions. Mitomycin C was given on the first postoperative day at two doses, 10 and 12 mg/m2. 5-Fluorouracil was given on postoperative days 2-5 at 15 and 20 mg/kg, respectively. Median area under the curve ratio i.p./i.v. was 117 for 5-fluorouracil and 21.6 for mitomycin C. Elevated intraportal levels of drug were observed for i.p. 5-fluorouracil but not for mitomycin C. The marked pharmacokinetic advantage of postoperative i.p. suggests that this treatment strategy should be considered in a clinical trial in patients at risk for progression of peritoneal carcinomatosis.

Chromatography, High Pressure Liquid↗
PubMed1990

Ondansetron: a new entity in emesis control.

Nausea and vomiting are serious problems for patients receiving cancer chemotherapy. Dopamine receptor and cholinergic receptor antagonism have been the target mechanism for agents used to combat drug-induced nausea and vomiting; more recently, blockade of serotonin receptors has been used for this indication. Current therapies are limited by extrapyramidal adverse effects, as well as drowsiness, sedation, respiratory depression, and cardiac effects. Ondansetron is an investigational serotonin antagonist that has documented effectiveness for cancer chemotherapy-induced emesis. Ondansetron appears to be well tolerated, with the possible exception of headaches and transient increases in liver enzymes. No extrapyramidal toxicities have been reported with this agent. While ondansetron looks promising, further studies are needed to fully define its role as an antiemetic.

Antiemetics↗
PubMed1989

Acral erythema secondary to high-dose cytosine arabinoside with pain worsened by cyclosporine infusions.

Acral erythema after high-dose cytosine arabinoside (Ara-C) has been described as a painful, sharply demarcated, and intense erythema of the palms and soles. This phenomenon occurred and is described in three out of three allogeneic bone marrow transplant (BMT) recipients who received high-dose Ara-C and total-body irradiation for conditioning therapy via the same protocol. These patients also received cyclosporine and methotrexate as prophylaxis for acute graft-versus-host disease. Two of the three patients experienced an increase in the pain associated with acral erythema during cyclosporine infusions and required large doses of narcotic analgesics. Since alcohol intensifies the pain of stomatitis and cyclosporine is manufactured in an alcohol base, the high alcohol content is suspect as the causative factor for this adverse reaction/drug interaction.

Adolescent↗
PubMed1989

Drug-induced toxicities associated with high-dose cytosine arabinoside infusions.

The frequency and significance of central nervous system (CNS), ocular, and dermatologic toxicities associated with high-dose cytosine arabinoside (HDARA-C) infusions was evaluated. Patients were selected from one of three Southeastern Cancer Study Group protocols using HDARA-C 2-3 g/m2 body surface area (BSA) and their medical records were reviewed to identify and document the frequency of the toxicities. Those exhibiting CNS toxicity were compared across age, sex, race, previous standard-dose ARA-C or HDARA-C therapy, and infusion rate for toxicity occurrence. Statistical analysis was performed using Fisher's exact test with p less than 0.05. Of the 53 patients evaluated, 37.7% exhibited CNS, 37.7% ocular, and 45.3% dermatologic toxicities. Of the risk factors evaluated, only increasing age and previous ARA-C therapy approached statistical significance. The CNS toxicities associated with HDARA-C are clinically significant since permanent damage may result. Ocular and dermatologic toxicities usually resolve without medical intervention when HDARA-C therapy is discontinued. Further study is necessary to determine appropriate prophylaxis for these toxicities.

Adolescent↗
PubMed1989

Rationale for integrating early postoperative intraperitoneal chemotherapy into the surgical treatment of gastrointestinal cancer.

A new concept in the natural history of gastrointestinal (GI) cancer suggests that recurrence of this malignancy can be separated into two types. Hematogenous and lymphatic metastases occur before surgical removal of the primary cancer. The spread of cancer to the resection site and to peritoneal surfaces occurs at the time of surgical removal of the primary tumor. Surgical trauma leads to a dispersal of malignant tumor emboli, which then implant within the raw tissue surfaces of the resection site and abraded peritoneal surfaces. Instillation of chemotherapy directly into the peritoneal cavity, as part of GI surgery, provides cytotoxic levels of drug that may change the natural history of GI cancer. The most common sites of disease recurrence have been, in the past, at the resection site and on peritoneal surfaces. With the optimal use of intraperitoneal chemotherapy, these sites of surgical treatment failure should no longer occur. Early phase I and II and pharmacologic studies suggest that an effective dose and schedule have been achieved, that toxicity is at reasonable levels, and that responses with small volumes of intra-abdominal cancer are exceptionally high. Chemotherapy that has an impact on the surgical event by decreasing cancer spread to the resection site and to peritoneal surfaces may significantly improve survival and quality of life in patients with GI cancer.

Antineoplastic Agents↗
PubMed1984

On the interaction of cobra venom protein cardiotoxins with erythrocytes.

The principally active hemolytic toxin (cardiotoxin) previously purified from the venom of the Thailand cobra, Naja naja siamensis, was shown to produce spontaneous twitching, contractures and membrane depolarization in sartorius muscles from the frog, Rana pipiens. Spontaneous twitching, observed at concentrations greater than 0.1 uM was completely abolished by addition of tetrodotoxin and not affected by d-tubocurarine. Dose and time dependent membrane depolarization of muscle fibers was observed to occur within 10-30 min at 0.2 to 1.0 uM concentrations of the toxin. These observations, taken together with an amino acid analysis characteristic of previously described cobra venom cardiotoxins, characterized this hemolytic toxin as a cardiotoxin. In the absence of EDTA the initial velocities of erythrocyte hemolysis for this toxin showed a sigmoidal concentration dependence which became hyperbolic in the presence of EDTA. The largest increases in hemolysis rates on addition of 1 mM EDTA were observed at low toxin concentrations. In the presence of EDTA extracellular and membrane associated divalent cations are complexed, thus alleviating their competition with toxin for binding to the membrane, a key and apparently rate-determining initial step which leads to hemolysis. In the presence of EDTA hemolysis rates increased linearly at low toxin concentration and reached an extrapolated maximum value at toxin concentrations at which, given its molecular dimensions, there are just sufficient toxin molecules to cover the entire membrane surface area provided by the erythrocytes.

Animals↗
PubMed1983

Treatment of L-asparaginase allergic reaction.

The treatment of an allergic reaction to L-asparaginase is discussed in the presentation of a case of a 26-year-old man with chronic myelogenous leukemia who was undergoing methotrexate-L-asparaginase rescue therapy. The possible mechanism of action of L-asparaginase is reviewed, and precautions for use of L-asparaginase in combination therapy with methotrexate are presented.

Adult↗