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Biomedical subjects

R L Wagner

Publications and source records attributed to R L Wagner.

At least 37 records · Page 2Linked to original sources
PubMed1997

Comparison of ampicillin/sulbactam versus clindamycin in the prevention of infection in patients undergoing head and neck surgery.

BACKGROUND: Patients requiring major oncologic head and neck surgery are at high risk for postoperative wound infection when the surgical site is contaminated by secretions from the upper aerodigestive tract. Studies to identify agents active in the prevention of postoperative wound infection may serve to reduce patient morbidity. METHODS: Patients scheduled for a major contaminated head and neck surgical procedure were randomly assigned to receive either ampicillin/sulbactam or clindamycin. Medication was administered 1 to 2 hours prior to surgery and every 6 hours, for a total of five doses. Postoperatively, patients were followed daily for the development of wound infection or other septic complication. RESULTS: A total of 242 patients were enrolled in the study; 119 received ampicillin/sulbactam, and 123 received clindamycin. A total of 169 patients were considered evaluable. Of the evaluable patients, 14% in each group developed a postoperative wound infection. There were no statistically significant differences between the number of days to onset of wound infection, nor was there a statistically significant difference in the rate of non-wound infections in the two groups. There were no statistically significant differences between the intent to treat group and the evaluable group of patients. CONCLUSION: It is concluded that ampicillin/sulbactam is as safe and effective as clindamycin in preventing postoperative wound infection following major head and neck surgery.

Adolescent↗
PubMed1996

A long-term assessment of adjuvant chemotherapy on outcome of patients with extracapsular spread of cervical metastases from squamous carcinoma of the head and neck.

BACKGROUND: Extracapsular spread (ECS) of cervical lymph node metastases of squamous cell carcinoma from head and neck sites portend poor prognosis. Therefore, a program of combined surgery, postoperative irradiation therapy, and adjuvant methotrexate and 5-fluorouracil (5-FU) was initiated in 1982 for such patients. METHOD: All patients operated on between June 1982 and December 1992 by the full-time faculty of the Department of Otolaryngology at the University of Pittsburgh School of Medicine were eligible and reported in this trial. All patients had negative surgical margins of excision of the primary carcinoma, and histologic evidence of cervical metastases with ECS. Postoperative irradiation included 50-60 cGy for 5 to 6 weeks followed by methotrexate and 5-FU administered on an outpatient basis on days 1 and 8 every 21 days. All patients were followed for 30 or more months for evidence of recurrent disease. RESULT: A total of 371 patients met eligibility criteria. Of this group, 53 (14%) were treated with surgery only, 187 (50%) received surgery and postoperative irradiation, and 131 (35%) received surgery, irradiation therapy, and chemotherapy. The primary site, extent of nodal involvement, and stage of the three patient groups were similar. However, performance status (Karnofsky) was best in the patients who received chemoradiation (average 90) when compared with those who received surgery and irradiation (average 80) or surgery only (average 70). Absolute disease free survival rate (30 months) was 9.5% in patients treated with surgery only, 34% in patients treated with surgery plus irradiation, and 53% in patients treated with surgery, irradiation, and chemotherapy. When adjusted for patients who died of intercurrent disease with less than 30 months follow-up, survival rates became 17%, 40%, and 58%, respectively. These differences are highly significant (P < 0.001). CONCLUSION: Results of this study suggest that postoperative chemoradiation may improve survival in patients with ECS of cervical metastases. Compliance with the chemoradiation was suboptimal and suggests that improved strategy must be developed.

Aged↗
PubMed1995

A structural role for hormone in the thyroid hormone receptor.

The crystal structure of the rat alpha 1 thyroid hormone receptor ligand-binding domain bound with a thyroid hormone agonist reveals that ligand is completely buried within the domain as part of the hydrophobic core. In addition, the carboxy-terminal activation domain forms an amphipathic helix, with its hydrophobic face constituting part of the hormone binding cavity. These observations suggest a structural role for ligand, in establishing the active conformation of the receptor, that is likely to underlie hormonal regulation of gene expression for the nuclear receptors.

Allosteric Regulation↗
PubMed1995

Cost analysis of antibiotic prophylaxis in clean head and neck surgery.

OBJECTIVE: This study was undertaken to assess the excess cost of hospitalization accrued to patients who develop postoperative wound infection following neck dissection in which the wound was not exposed to secretions from the upper aerodigestive tract. DESIGN: A retrospective cohort of patients who underwent "clean" neck dissection from 1976 to 1989 were evaluated. Antibiotic administration (yes or no), post-operative wound infection (yes or no), and duration and cost of hospitalization were assessed. SETTING: All surgeries were performed in a university medical center. PATIENTS: All patients underwent neck dissection in which the procedure was clean, ie, there was no exposure to secretions from the upper aerodigestive tract. MAIN OUTCOME MEASURES: Patients were assessed to determine administration of antibiotics (yes or no), development of postoperative wound infection (yes or no), and duration and cost of hospitalization. RESULTS: Wound infection developed in 10 (10%) of 99 patients who did not receive antibiotics. Of 93 patients who received perioperative antibiotics, three (3.3%) developed wound infection. This difference was not statistically significant. The type II (beta) error was greater than 0.2, suggesting that a significant difference may have been missed (false-negative) as a result of the small number of patients studied. The excess cost accrued to each patient who developed a postoperative wound infection was in excess of $36,000 (1992 dollars). The cost of administration of antibiotic prophylaxis to 100 patients is less than this amount. CONCLUSION: The decision to withhold antibiotic prophylaxis should not be made in an effort to reduce hospital costs.

Adult↗
PubMed1995

Superiority of the T and N integer score (TANIS) staging system for squamous cell carcinoma of the oral cavity.

An alternative to the TNM classification system has been proposed for patients with head and neck cancer. The T and N integer score (TANIS) system adds the integer values of T and N classifications. The TNM and TANIS staging systems were retrospectively evaluated for 186 patients with squamous cell carcinoma of the oral cavity (tongue and floor of mouth). The TANIS system was found to better separate the patients into prognostic groups and allowed a more accurate prediction of disease-free survival.

Carcinoma, Squamous Cell↗
PubMed1995

Regulation of ornithine decarboxylase mRNA levels in human breast cancer cells: pattern of expression and involvement of core enhancer promoter element.

Ornithine decarboxylase (ODC) expression is increased by growth factors and is obligatory for progression through the cell cycle in a wide variety of cell types. In this study, a variant human ODC cDNA was identified, sequenced, and used to probe mRNA levels in human breast tumor cell lines and xenografts. ODC mRNA was elevated about 3-fold in estrogen receptor-negative (ER-) tumors (MDA-MB-231) when compared with ER-positive (ER+) tumors (MCF-7), as assessed by quantitative autoradiographic analysis of in situ hybridization experiments. The pattern of ODC mRNA in MDA-MB-231 (ER-) xenografts was polarized to the extreme periphery of the tumor, whereas the distribution of ODC mRNA was more evenly distributed in MCF-7 (ER+) xenografts. This correlates with hematoxylin and eosin staining patterns, suggesting that ER+ and ER- xenografts have a differential dependence on host vasculature for growth factor supply. ODC mRNA was elevated 5-fold in MDA-MB-231 cells versus MCF-7 cells when analyzed in cell culture. These relative mRNA levels correlate with increased levels of "core" enhancer binding nuclear proteins in MDA-MB-231 cells over that detected in MCF-7 cells.

Animals↗
PubMed1994

Preliminary crystallographic studies of the ligand-binding domain of the thyroid hormone receptor complexed with triiodothyronine.

A truncated, recombinant form of the thyroid hormone receptor, including the hormone binding domain, has been co-crystallized with the hormone T3. The crystals are monoclinic, most likely space group P2, with two molecules per asymmetric unit and cell dimensions a = 63.6 A, b = 80.8 A, c = 100.9 A and beta = 92.1 degrees. The crystals diffract to only medium resolution and decay rapidly in the X-ray beam using laboratory sources. By contrast, high resolution, high-quality data are obtained using synchrotron radiation in conjunction with cryocrystallography.

Binding Sites↗
PubMed1994

Exogenous acetate reconstitutes the enzymatic activity of trypsin Asp189Ser.

The specificity of trypsin for Arg- and Lys-containing substrates depends upon the presence of Asp189 at the base of the primary binding pocket. The crystal structure of anionic rat trypsin D189S complexed with BPTI reveals that removal of the aspartate side chain permits the binding of a well-ordered acetate ion in a similar position. The acetate makes polar interactions with Gly226, Tyr228, and several water molecules and is further accommodated by rotation of the Ser189 side chain out of the binding pocket. The carboxylate group of the acetate anion is oriented toward the substrate in a manner similar to that of Asp189 and Asp226 in wild-type trypsin and trypsin D189G/G226D. Evaluation of kinetic parameters for amide substrate cleavage by trypsin D189S shows that high concentrations of acetate increase the catalytic efficiency of the enzyme by as much as 300-fold. Under these conditions, the rate of substrate turnover toward a peptidylarginine amide substrate equals that of wild-type trypsin. These data demonstrate that the well-established requirement for a negatively charged moiety at the base of the trypsin specificity pocket may be fulfilled by a noncovalently bound ligand. The binding pocket of this variant maintains a trypsin-like conformation, explaining the inability of the mutant enzyme to efficiently hydrolyze chymotrypsin substrates possessing Phe in the P1 position.

Acetates↗
PubMed1994

Activation of D1 and D2 dopamine receptors inhibits protein kinase C activity in striatal synaptoneurosomes.

The effects of D1 and D2 dopamine ligands on protein kinase C (PKC) activity were examined in synaptoneurosomes. Incubation with D1 agonists (SKF 38393, fenodopam), in the presence of calcium, decreased the soluble and increased the particulate PKC activity. These effects were reversed by SCH 23390, which by itself had the opposite effect of increasing the soluble and decreasing the particulate PKC activity. In contrast, incubation with the D2 agonists [LY 171555, (+)-3-(3-hydroxyphenyl)-N-n-propylpiperidine, RU 24213] increased the soluble and decreased the particulate PKC activity. These effects were reversed by sulpiride. (-)-3-(3-Hydroxyphenyl)-N-n-propylpiperidine had a D2 antagonist profile. Apomorphine showed a biphasic dose-response change; i.e., it decreased particulate PKC activity at the D2 receptor at low concentrations (0.1 microM) and increased it at the D1 receptor at higher concentrations (10 microM). Pretreatment with tetrodotoxin or omission of calcium in the incubation medium did not alter the responses of the D2 agonists, but it reversed the changes in PKC activity induced by the D1 agonists and converted the biphasic response of apomorphine to a monophasic inhibition. These results indicate that (1)D1 and D2 dopamine receptors are negatively coupled to PKC and (2) the increase in particulate PKC activity seen with the D1 drugs in the presence of calcium is mediated indirectly via a transneuronal effect.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1994

Microlaryngoscopic surgery for T1 glottic lesions: a cost-effective option.

Excision of squamous cell carcinoma of the vocal cord using microlaryngoscopy (ML) with or without laser is a cost-effective treatment option in highly selected patients. A retrospective review of 50 cases of invasive and microinvasive squamous cell carcinoma demonstrated a failure rate of 8% (4 patients), all of whom were successfully salvaged by hemilaryngectomy (1 patient) or irradiation (3 patients). Other treatment options for T1 glottic lesions include hemilaryngectomy or radiotherapy, yielding similar cure rates of 95% and 67% to 93%, respectively. Investigation of the potential savings by extrapolating 1992 health care costs into the treatment options for T1 glottic carcinoma resulted in costs of $12,956 per patient for ML, while hemilaryngectomy averaged $35,616 per patient and radiotherapy netted costs of $32,588 per patient. Extrapolating these costs to a theoretic group of 100 patients, ML provided savings of 2.4 million dollars when compared to the other treatment modalities. In selected patients, ML for T1 glottic cancer provides an effective therapeutic modality suited to our cost-conscious environment.

Adult↗
PubMed1994

The efficacy of topical antibiotic prophylaxis for contaminated head and neck surgery.

This study was undertaken to determine the feasibility of using perioperative topical antibiotics in contaminated head and neck surgery and to standardize the culture methodology (both qualitative and quantitative) which could serve as bacteriologic endpoints for evaluation. Following preliminary studies to establish oral cavity indicator organisms and the impact of a single antibiotic mouthwash dose on oral microflora, 10 consecutive patients undergoing contaminated head and neck surgery were recruited into a clinical trial where clindamycin mouthwash and intraoperative irrigation containing clindamycin were used instead of traditional parenteral antibiotics. The bacteriologic efficacy of topical clindamycin was assessed by comparing the presence of four indicator microorganisms (two aerobic and two anaerobic) cultured from two oral cavity culture sites before and after antibiotic prophylaxis. The patients included in the study underwent total laryngectomy plus neck dissection(s) for laryngeal or hypopharyngeal carcinoma from 1991 to 1992 at a large university hospital specializing in head and neck cancer surgery. The main outcome measures used were the development of a postoperative wound infection and quantitative and qualitative bacteriology of the intraoperative neck wound and postoperative oral cavity. Two aerobic and two anaerobic organisms proved useful as a practical indicator for bacteriologic efficacy. Preoperative mouthwash resulted in a 99% reduction of both aerobic and anaerobic bacteria in intraoperatively cultured neck sites. Irrigation during surgery with the clindamycin solution further reduced the bacterial neck counts by an additional 90%. There was a consistent overgrowth of Hemophilus species on postoperative oral cavity cultures. No patient developed a postoperative wound infection. A topical prophylactic antibiotic alone was efficacious and safe for patients undergoing major contaminated head and neck surgery. Culture methods for assessment of bacteriologic efficacy were reproducible and cost-effective. This pilot study furnishes the ethical and scientific basis for large-scale prospective trials comparing topical versus parenteral antimicrobial agents.

Administration, Topical↗
PubMed1993

Outcome of open surgical therapy for glottic carcinoma.

A retrospective review was undertaken of the medical records of 270 patients with carcinoma of the glottic larynx. Patients were staged pathologically, and clinical pathologic correlates were made with outcome. In 92 patients with early glottic cancer, the 2-year rate of no evidence of disease for T1 was 98%, and for T2, 84%. Vertical partial laryngectomy resulted in voice preservation in 89%. Patients treated for advanced (T3 or T4) glottic carcinoma underwent total laryngectomy with or without neck dissection. Cervical nodes were involved in 22% of T3 and 41% of T4 patients at the time of treatment. Survival with no evidence of disease was chiefly determined by the development of regional recurrence, distant metastasis, and new primary cancer. Distant metastasis was associated with extracapsular spread (p = .003). Patients treated for T4 glottic carcinoma with neck dissection had improved survival compared with patients treated with laryngectomy alone (p = .006). Improved survival must be aimed at regional control, prevention, and management of distant metastasis and new primary carcinoma.

Adult↗
PubMed1992

Multiple promoter elements govern expression of the human ornithine decarboxylase gene in colon carcinoma cells.

Overexpression of the ornithine decarboxylase (ODC) gene may be important to the development and maintenance of colonic neoplasms, as well as tumors in general. In this study, we examined the promoter elements governing constitutive expression of the human ODC gene in HCT 116 human colon carcinoma cells and, for comparison, K562 human erythro-leukemia cells. It was determined by functional analysis that the promoter elements responsible reside within the 378 bp immediately upstream from the transcription start site. Within this sequence, there are at least three regions that modulate the efficiency of the ODC promoter cooperatively. Both DNA bandshift and footprint assays demonstrated all three regions to be rich in sites that bind to nuclear proteins isolated from HCT 116 and K562 cells; the protein binding pattern of non-transformed, diploid fibroblasts was found to be much less complex. Several of the protein binding sequences have little or no homology to common regulatory elements. We suggest that the constitutive activity of the ODC gene in HCT 116 colon carcinoma cells, and perhaps transformed cells in general, involves a complex interaction of multiple regulatory sequences and their associated nuclear proteins. Finally, the saturation of the promoter in these transformed cell lines suggests that high levels of protein binding in the ODC promoter may contribute to elevated constitutive expression of this gene.

Base Sequence↗
PubMed1992

Prophylactic antibiotics for head and neck surgery with flap reconstruction.

The leading cause of postoperative morbidity in patients undergoing major head and neck surgical procedures is postoperative infection. This prospective randomized multi-institutional clinical trial was designed to compare the effectiveness of clindamycin phosphate and high-dose cefazolin sodium therapy in preventing postoperative wound sepsis in patients undergoing contaminated head and neck surgical procedures in which flap reconstruction was required. Either clindamycin phosphate (900 mg) or cefazolin sodium (2 g) therapy was instituted intravenously prior to surgery and continued every 8 hours, for a total of 24 hours. The patients received postoperative follow-up, and the wounds were graded according to the worst condition observed. One hundred cases were evaluated. Fifty-one patients received clindamycin and 49 patients received high doses of cefazolin; wound infection developed in 10 patients (19.6%) and 11 patients (21.6%), respectively. This difference was not statistically significant. The average duration of surgery was approximately 8 hours for both the infected and the noninfected groups of patients. High-dose cefazolin and clindamycin have similar efficacy when administered prophylactically under these circumstances. Reconstruction with free vascularized tissue may aid in reducing postoperative wound infection.

Cefazolin↗
PubMed1992

The lack of utility of a tumor marker panel in head and neck carcinoma. Squamous cell carcinoma antigen, carcinoembryonic antigen, lipid-associated sialic acid, and CA-125.

An ideal tumor marker should be sensitive in tumor-bearing patients while having adequate specificity so that controls do not demonstrate the marker. To date, a single circulating marker has not been identified for squamous cell carcinoma of the head and neck. This study evaluates a panel including squamous cell carcinoma radioimmunoassay, lipid-associated sialic acid, carcinoembryonic antigen, and CA-125. In this population of patients with cancer, serum samples from 101 patients and 88 controls were evaluated. The squamous cell carcinoma radioimmunoassay was the most sensitive marker identified (47.5%), while carcinoembryonic antigen level was elevated in 40.6%, lipid-associated sialic acid level in only 16.8%, and CA-125 level in 7.9%. False-positive results were found with all markers, including squamous cell carcinoma radioimmunoassay (18.2%), carcinoembryonic antigen (18.2%), lipid-associated sialic acid (10.2%), and CA-125 (15.9%). Various combinations of markers did not significantly improve either specificity or sensitivity. Available tumor markers are inadequate for diagnostic purposes in patients with squamous cell carcinoma of the head and neck.

Antigens, Neoplasm↗
PubMed1992

Transmandibular approaches to the oral cavity and oropharynx. A functional assessment.

The records of patients undergoing transmandibular approaches to soft-tissue carcinoma of the oral cavity and oropharynx were reviewed retrospectively. Thirty-nine patients requiring lateral segmental hemimandibulectomy and 45 patients requiring a mandibulotomy were identified. None of the patients given mandibulectomy underwent bone reconstruction, while all of the patients with mandibulotomy had repair at the completion of the case. A total of 53 patients were available for recall and functional assessment. Patients with mandibulotomy did not experience significant dysfunction of the temporomandibular joint. Patients with mandibulectomy demonstrated increasing amounts of eccentric occlusion; however, this did not affect diet and was not reported to be uncomfortable by these patients. When feasible, preservation of the mandible yielded an improved aesthetic result; however, functional results in patients requiring mandibulectomy compare favorably with those obtained after mandibulotomy and repair.

Adolescent↗