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Biomedical subjects

G L Adams

Publications and source records attributed to G L Adams.

At least 37 records · Page 2Linked to original sources

Elevated protein kinase CK2 activity in chromatin of head and neck tumors: association with malignant transformation.

We hypothesized that malignant transformation of normal mucosa of the upper aerodigestive tract to squamous cell carcinoma of the head and neck (SCCHN) might be associated with altered CK2 activity in the chromatin compartment of these tumors. We measured CK2 activity in the cytosol and chromatin of 7 surgical specimens of SCCHN, and 5 specimens of normal oropharyngeal mucosa from non-smokers/non-drinkers. CK2 activity in SCCHN tumors was significantly elevated in both the nuclear chromatin (P < 0.0005) and cytosolic (P <0.04) compartments relative to normal mucosa. These data suggest that activation of dysregulation of the chromatin-associated CK2 signal may play a role in the pathobiology od SCCHN.

Amino Acid Sequence↗

Inhibition of head and neck tumor cell growth with arachidonic acid metabolism inhibition.

Head and neck tumors are known to synthesize arachidonic acid metabolites. The authors have postulated that these substances may confer growth advantage to cancer cells, and by interfering with arachidonic acid metabolism squamous cancer growth may be altered. The tongue derived squamous carcinoma cell line, SCC-25, was treated with three leukotriene synthesis inhibitors and indomethacin. A dose-dependent decrease in DNA synthesis occurred with leukotriene inhibition, but not prostaglandin inhibition. All leukotriene synthesis inhibitors produced a dramatic and immediate effect ( > 70% inhibition by 4 hours) without cytotoxicity ( > 90% trypan blue exclusion). Cell populations at 96 hours were decreased when compared to control populations. In conclusion, leukotrienes or other lipoxygenase products may play a role as growth factors for squamous cell carcinoma, and arachidonic acid inhibition may be a novel target for chemotherapeutic intervention.

Arachidonic Acid↗

Treatment of head and neck hemangiomas with recombinant interferon alpha 2B.

Fifteen patients with head and neck hemangiomas were treated with systemic recombinant interferon alpha 2b (rIFNalpha2b, Schering). There were 14 infants and 1 adult in the group, ranging in age from 5 weeks to 24 years old. Of the 15 patients in the group, 5 had involvement of the airway. Three of the patients had previously failed alternative systemic therapy. Twelve patients have had a beneficial response. Ten patients have completed the therapy and have been off interferon from 6 to 53 months without reappearance or progression of the disease. Two patients are currently on the therapy with resolving lesions. Three patients had minimal response and underwent successful surgical resection. No major toxicity was encountered during the therapy. Our experience demonstrates that rIFNalpha2b is a well-tolerated and effective therapy for hemangiomas of the head and neck that require intervention.

Adolescent↗

Microhardness and scanning electron microscopy analysis of Nd:YAG laser and acid treatment effects in dentin.

Laser irradiation at and above parameters producing the modification threshold for dentin causes structural changes to the dentin surface. This study determined the microhardness of dentin before and after laser modification and acid treatment using a repeated-measures design. Seven dentin sections (4 mm in thickness) were cut from freshly extracted non-carious third molars using a diamond saw. The middle occlusal third was used as the test dentin surface. One section served as a control (C); three received laser modification (L) and then acid treatment (L + A); and three received acid (A) and then laser treatment (A + L). Laser modification was made using a pulsed (120 microseconds) fiber-optic-delivered (500 microns diameter) Nd:YAG (lambda = 1.06 microns) laser at the physical modification threshold of 207 J/cm2. Acid treatment consisted of 10% nitric acid applied for 45 seconds. Twenty Knoop indentation microhardness measurements (KHN) were obtained using 300 g force engaged for 15 seconds for each section before and after each treatment (n = 400). Knoop microhardness values recorded: C = 62 +/- 3; L = 149 +/- 35; A = 24 +/- 5; L + A = 40 +/- 16; and A + L = 33 +/- 5. Multifactor-repeated measures, with analysis of variance (ANOVA; p < or = 0.05), indicated significant differences between all treatment groups. Scanning electron microscopy analysis of dentin surfaces documented unique surface morphology for all treatment conditions. Laser modification of dentin before or after acid treatment increased dentin microhardness.

Adult↗

Patterns of recurrence after carbon dioxide laser excision of intraoral squamous cell carcinoma.

OBJECTIVE: To examine retrospectively consecutive patients treated with carbon dioxide laser excision of intraoral squamous cell carcinoma for the patterns of recurrence based on the location of the initial primary tumor and on the tumor stage. DESIGN: Retrospective chart review. SETTING: Tertiary care center including a university hospital and a Veterans Affairs Medical Center. PROCEDURES AND PATIENTS: Sixty-one procedures performed on 51 consecutive patients. The only patients not included were three who were unavailable for follow-up. The average follow-up was 32 months. If the patients whose follow-up was limited because of death are excluded, the average follow-up was 40 months. MAIN OUTCOME MEASURES: Incidence of recurrence, time to recurrence, development of second intraoral primary lesions or pulmonary metastases, and cause of death. RESULTS: A nearly equal incidence of recurrence irrespective of site of lesion (tongue, 42%; floor of mouth, 40%; and other oral cavity sites, 45%). Determinate survival differed by stage. Patients with T1 lesions showed a determinate survival rate of 80%; those with T2 or T3 lesions had a determinate survival rate of 57%; and those treated for recurrent disease had a determinate survival rate of 44%. CONCLUSIONS: Carbon dioxide laser excision of intraoral squamous cell carcinoma is a useful, advantageous method, but it appears to offer no advantage for recurrence over standard methods. Appropriate management of neck disease in patients with intraoral squamous cell carcinoma must be carefully considered. Patients with this potentially aggressive form of cancer deserve long-term follow-up.

Adult↗

Association of elevated protein kinase CK2 activity with aggressive behavior of squamous cell carcinoma of the head and neck.

BACKGROUND: Protein kinase CK2 (also known as casein kinase 2) is a messenger-independent protein serine/threonine kinase ubiquitously distributed in eukaryotes. CK2 has been found to phosphorylate a wide variety of cytosolic and nuclear substrates which are intimately involved in regulation of DNA, RNA, and protein synthesis, and differentiation. We therefore addressed the hypothesis that malignant transformation of upper aerodigestive tract mucosa to squamous cell carcinoma of the head and neck (SCCHN) might be associated with altered CK2 activity. MATERIALS AND METHODS: To this end, we subjected surgical specimens of SCCHN tumors and of normal oropharyngeal mucosa to subcellular fractionation. We then quantitated CK2 activity in cytosol and nuclei of these specimens using a CK2-specific peptide substrate (Arg-Arg-Arg-Glu-Glu-Glu-Thr-Glu-Glu-Glu). RESULTS: We found that CK2 activity was significantly elevated in both nuclear (p < 0.0005) and cytosolic (p < 0.0034) compartments of SCCHN tumors, relative to normal oropharyngeal mucosa. Moreover, CK2 activity in the cellular cytosolic fraction of SCCHN tumors was associated with less differentiated histologic grade (p < 0.037), positive nodal metastatic status (p < 0.056), and a poor clinical outcome (p < 0.028). Kaplan-Meier cumulative survival analysis revealed greatly reduced survival in the high-CK2 activity patient group, with high statistical significance (p < 0.023). CONCLUSIONS: These preliminary data reveal that malignant transformation of the upper aerodigestive tract mucosa is associated with altered CK2 activity. The results further suggest that dysregulation of this protein kinase may play a significant role in the pathobiology of SCCHN, and that CK2 activity may be a prognostic indicator in this malignancy.

Adult↗

Irradiated soft tissue and its management.

The healing of a surgical wound is significantly affected by radiation. Radiation can affect all cells within its treatment field, thus making irradiated tissue more susceptible to trauma, infection, and irritation. In the irradiated patient, careful preoperative planning and a preventive approach to optimize conditions for wound healing are crucial to minimizing complications. This article describes the principles and management of common complications seen from irradiated soft-tissue wounds of the head and neck.

Combined Modality Therapy↗

Phase Ib trial of the effect of peritumoral and intranodal injections of interleukin-2 in patients with advanced squamous cell carcinoma of the head and neck: an Eastern Cooperative Oncology Group trial.

Thirty-six patients with unresectable squamous cell carcinoma of the head and neck were entered into a phase Ib trial evaluating the toxicity, maximally tolerated dose (MTD), and immunomodulating effects of locally administered interleukin-2 (IL-2). Patients received daily IL-2 injected perilesionally in divided doses in each of four quadrants and bilaterally into the superior jugular lymph nodes. The dose of IL-2 began at 200 U/day and was escalated to 4 x 10(6) U/day in groups of six patients. Overall, regionally administered IL-2 was well tolerated. The most frequently encountered toxicities were fever, hepatotoxicity, and hypotension. Dose-limiting toxicity was encountered at 4 x 10(6) U. Of the 36 patients treated, 2 partial responses were noted at 2,000 and 4 x 10(6) U. We conclude that regionally administered IL-2 is well tolerated in patients with head and neck cancer and that the MTD is 2 x 10(6) U/day, similar to what has been reported with systemically administered IL-2. Although the overall response rate was low, it may be improved with prolonged administration of IL-2 or by combining it with other biologic or cytotoxic agents.

Adult↗

Tobacco smoke and otitis media in the chinchilla model.

To determine whether tobacco smoke contributes to the pathogenesis of acute otitis media, chinchillas were exposed to mainstream tobacco smoke or sham conditions (cigarettes not lit) in a Walton smoke exposure machine for 20-minute cycles two or three times daily. After 6 to 8 weeks of daily exposure, 12 chinchillas were nasally injected with Streptococcus pneumoniae, and 18 chinchillas were injected into both middle ears with nontypable Haemophilus influenzae. Smoke or sham exposures were continued for 2 to 4 weeks after injection. Otitis media developed in none of the 12 nasally injected chinchillas and in all 18 chinchillas whose middle ears were injected with nontypable Haemophilus influenzae. Persistence of middle ear effusion and persistence of nontypable Haemophilus influenzae in the middle ear effusion were not different between the smoke- and sham-exposed groups. This suggests that mainstream smoke exposure does not change the natural course of otitis media in the chinchilla model.

Acute Disease↗

Concurrent radiation therapy and chemotherapy for locally unresectable squamous cell head and neck cancer: an Eastern Cooperative Oncology Group pilot study.

PURPOSE: The feasibility and success of an intensive chemoradiotherapeutic protocol for patients with locally advanced, unresectable squamous cell head and neck cancer was tested in this limited-institution, Eastern Cooperative Oncology Group phase II pilot study. MATERIALS AND METHODS: Between December 1987 and September 1989, 57 patients were entered onto this trial. The treatment protocol consisted of three courses of a 4-day continuous fluorouracil infusion, a single cisplatin bolus injection, and concurrent split-course radiotherapy. After 30 Gy of radiation and two chemotherapy courses, patients were evaluated for response and for the possibility of surgical resection. RESULTS: Fifty-five of 57 registered patients are assessable for toxicity and 52 are assessable for response and survival. Toxicity was significant, but tolerable, although there were three toxic deaths. A complete response to this treatment was ultimately achieved by 77% of patients. Twenty-four patients remain relapse-free. The projected Kaplan-Meier 4-year relapse-free survival rate is 45% and the overall survival rate is 49%. Median relapse-free and overall survival durations are 26 and 37 months, respectively. Of the 28 treatment failures, 79% were locoregional. Fourteen patients underwent surgery. Six remain relapse-free. CONCLUSION: This aggressive concurrent chemoradiotherapy protocol appears feasible within a cooperative group. Treatment results are promising and appear durable. A randomized phase III clinical trial is currently underway.

Adult↗

Administration of a prostaglandin synthetase inhibitor associated with an increased immune cell infiltrate in squamous cell carcinoma of the head and neck.

Squamous cell carcinoma of the head and neck produces a prostaglandin, PGE2, a potent inhibitor of cellular immune responses. We tested the effects of prostaglandin synthetase inhibition on the infiltration of squamous cell carcinoma of the head and neck with host lymphocytes. Tumor tissue samples were obtained from six patients (age range, 51 to 72 years) who presented with squamous cell carcinoma of the head and neck before and after 14 days of treatment with indomethacin (50 mg administered orally three times a day). Tumor-infiltrating immune cells were assayed in frozen tissue samples by indirect immunofluorescence. An eightfold increase in CD2+ lymphocytes compared with pretreatment tissue was observed. The number of CD4 and CD8 lymphocytes increased similarly. CD57 lymphocytes increased 15-fold and CD11b cells increased 11-fold. No infiltrating B-cell populations were evident. Double-labeling studies revealed that the mononuclear cells were located outside blood vessel walls, indicating that they had infiltrated the tumor parenchyma. Our findings demonstrate that the administration of indomethacin is associated with the increased immune cell infiltration of squamous cell carcinoma of the head and neck. This suggests that inhibition of PGE2 synthesis as it occurs in the tumor and or systemically may contribute to the homing of mononuclear cells to the tumor. These data suggest a mechanism to account for the clinical response to indomethacin previously reported in squamous cell carcinoma.

Aged↗

Intracranial complications of paranasal sinusitis: a combined institutional review.

Intracranial complications of paranasal sinusitis constitute true surgical and medical emergencies. The charts of all patients (n = 649) admitted for acute or chronic sinusitis to the University of Minnesota Hospital and to the University of Michigan Medical Center during a 13-year period (1975 to 1988) were retrospectively reviewed to determine the incidence of complications. The clinical presentation, bacteriology, involved sinuses, influencing host factors, white blood cell count on presentation, length of hospitalization, and postinterventional complications are presented. Twenty-four patients with intracranial complications from paranasal sinusitis are studied for an incidence of 3.7%. Aggressive medical and semi-emergent surgical intervention are required to prevent excessive morbidity and/or mortality. Intracranial complications included subdural empyema, frontal lobe abscesses, intrahemispheric abscesses, cavernous and superior sagittal sinus thrombosis, and osteomyelitis.

Adolescent↗

Lysozyme levels in middle ear effusion and serum in otitis media.

Lysozyme concentrations in middle ear effusion and serum were determined in patients with otitis media with effusion. Lysozyme concentrations in middle ear effusion were significantly higher than in serum. Children with mucoid otitis media showed significantly higher levels of lysozyme in middle ear effusion than children with serous otitis media and adults with otitis media with effusion. Higher levels of lysozyme were observed in the group of children younger than 5 years old compared with the age group of 6- to 10-year-olds. Lysozyme concentrations of middle ear effusion in adults were significantly lower than those of mucoid otitis media in children. These results indicate that lysozyme plays an important role in the disease process of otitis media.

Adult↗

Respiratory papillomas: presentation before six months.

The prognosis of respiratory papillomatosis (RP) in newborns appears to be less favorable than in infants and older children. In this series of four patients who developed symptoms of the disease within the first 6 months of life, the mortality was 100%. In these premature and term newborn infants, endoscopic laser surgery and medical and immunologic therapy were unable to control the growth of RP. Meticulous local removal of the airway lesions is the most reliable form of management.

Diseases in Twins↗

Survival statistics for multiple primaries in head and neck cancer.

The recognition of a second primary carcinoma in a patient with known head and neck cancer is considered a poor prognostic sign. However, its true implication for patient survival is not known. A retrospective 10-year study showed that second primary malignancies developed in 207 of 875 patients. Second primary malignancies were most commonly associated with glottic index tumors, followed by floor of mouth tumors. The second primary was most likely to occur at a time interval of 1.5 years from diagnosis of the index tumor. Second primary neoplasms were more likely to develop in patients whose original head and neck tumor was stage I or II, or whose histopathology showed well or moderately well differentiation. Patients with head and neck cancer in whom a second upper aerodigestive tract tumor develops have a 75% chance of 1-year survival, but only a 25% chance of 5-year survival. The average time from diagnosis of second primary to the time of death was 2.3 years. If we are to increase the survival time of our patients with head and neck cancer, we must consider that a second primary will develop in one of four patients. We must therefore consider the high risk of second primary malignancy when formulating the original treatment plan for a patient manifesting his or her first head and neck cancer.

Adult↗