A pivot-shifting palate flap for enhanced exposure of the posterior choanae and nasopharynx.
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Chordoma↗
Biomedical subjects
R B Sessions
Publications and source records attributed to R B Sessions.
Modeling of substrate and inhibitor binding to phospholipase A2.
Molecular graphics and molecular mechanics techniques have been used to study the mode of ligand binding and mechanism of action of the enzyme phospholipase A2. A substrate-enzyme complex was constructed based on the crystal structure of the apoenzyme. The complex was minimized to relieve initial strain, and the structural and energetic features of the resultant complex analyzed in detail, at the molecular and residue level. The minimized complex was then used as a basis for examining the action of the enzyme on modified substrates, binding of inhibitors to the enzyme, and possible reaction intermediate complexes. The model is compatible with the suggested mechanism of hydrolysis and with experimental data about stereoselectivity, efficiency of hydrolysis of modified substrates, and inhibitor potency. In conclusion, the model can be used as a tool in evaluating new ligands as possible substrates and in the rational design of inhibitors, for the therapeutic treatment of diseases such as rheumatoid arthritis, atherosclerosis, and asthma.
Amino Acid Sequence↗
A prediction of the three-dimensional structure of maize NADP(+)-dependent malate dehydrogenase which explains aspects of light-dependent regulation unique to plant enzymes.
A model has been built for the plant NADP-malate dehydrogenase from Zea mays, a key enzyme in photosynthesis, which undergoes light-dependent regulation. The model was based on sequence and presumed structural homology to the known three-dimensional structure of mammalian porcine cytosolic NAD-malate dehydrogenase. A cystine-loop present in an extended C-terminal region of plant NADP-malate dehydrogenases was modelled using molecular mechanics and computer graphical methods, based on the assumption that a disulphide bridge exists in the inactive form of the enzyme between Cys351 and Cys363. The predicted conformation of the intact C-terminal cystine-loop suggests that the extended polypeptide will bind in the active centre and inhibit enzyme activity. Another ionizable cysteine residue in the active site is predicted to control the charge of the catalytic His215 and might be responsible for the uniquely tight binding of the positively charged nicotinamide ring of NADP+ in this and other C4 and C3 plant NADP-malate dehydrogenases.
Amino Acid Sequence↗
Nasopharyngeal brachytherapy with access via a transpalatal flap.
We used a posteriorly based transpalatal flap for interstitial nasopharyngeal brachytherapy in five patients with nasopharyngeal carcinoma. All of these implants were done with iodine 125 seeds. The disease in three of five patients has been controlled locally for 27, 30, and 40 months, respectively. Two patients experienced local failure and died. There have been no palatal healing problems despite high doses of previous radiation in all of our patients. No palatal incompetence has been seen. This technique appears safe and should be considered for discrete lesions of the high posterior or superior nasopharynx that cannot be approached by less invasive methods.
Adult↗
Base-of-tongue cancer treated with external beam irradiation plus brachytherapy: oncologic and functional outcome.
Between January 1981 and June 1990, 36 previously untreated patients with squamous cancer of the base of the tongue were treated with radiation therapy. This therapy consisted of a 5,000-5,400-cGy external beam plus a 2,000-3,000-cGy boost to the base of the tongue with an iridium-192 implant. Necks with negative nodes were only irradiated, while necks with positive nodes were treated with irradiation plus neck dissection. Actuarial local control and survival at 2 years were 87.5%. Neck control was achieved in 35 of 36 patients. When implantation was performed with the nonlooping technique, the injury rate was statistically higher than in patients who underwent implantation with the looping technique (P = .02). Thirty patients participated in a function assessment involving a Performance Status Scale for patients with head and neck cancer. The authors concluded that management of base-of-tongue cancer with external beam irradiation plus brachytherapy is both oncologically and functionally successful.
Adult↗
An analysis of prognostic factors in cutaneous neuroendocrine carcinoma.
Since the first report of cutaneous neuroendocrine carcinoma (Merkel cell carcinoma) in 1972, knowledge of the biological behavior of this tumor has continued to increase. This study reviews three previously unreported cases in addition to reports on 429 patients collected from the literature. The presenting features of these 306 patients were analyzed for frequency and then were analyzed by the Cox proportional hazard model for the relationship of each to recurrence and outcome. This study confirms that cutaneous neuroendocrine carcinoma is an aggressive disease; that the most common cause of death in these patients is by distant metastasis; and that men have succumbed more frequently than women. As a result of this study, aggressive treatment of cutaneous neuroendocrine carcinoma is recommended, especially in the male patient.
Aged↗
Aspartame and dizziness: preliminary results of a prospective, nonblinded, prevalence and attempted cross-over study.
Aspartame is a low-calorie food sweetener recently approved by the FDA for general human consumption. One of us (AJG) treated a patient whose symptoms of episodic vertigo and continuous unsteadiness resolved upon ceasing aspartame intake. A literature review revealed that although dizziness has been associated with aspartame intake, no systematic study of the problem exists. As an initial attempt to ascertain the prevalence of aspartame-related dizziness in an otolaryngologic clinic, we elected to study prospectively all patients entering with the complaint of vertigo by means of a standardized questionnaire. Those patients determined to consume aspartame were further studied in a nonblinded manner to see if aspartame intake could be correlated to symptomatology. A cross-over limb was also attempted, but no patient would participate. This presentation details the case history of the propositus patient and the preliminary results of the currently ongoing prospective study.
Adult↗
Standardizing neck dissection terminology. Official report of the Academy's Committee for Head and Neck Surgery and Oncology.
The emergence of the multitude of modified techniques for neck dissection procedure has resulted in a nomenclature system that is nonuniform. To eliminate potential misinterpretation, overlap, and lack of standardization, the Academy's Committee for Head and Neck Surgery and Oncology, with input from the Education Committee of the American Society of Head and Neck Surgery, has developed a classification system for these procedures. This has now been adopted by the American Academy of Otolaryngology-Head and Neck Surgery. The classification is based on the following concepts: (1) radical neck dissection is the fundamental procedure with which all other neck dissections are compared, (2) modified radical neck dissection denotes preservation of one or more nonlymphatic structure(s), (3) selective neck dissection denotes preservation of one or more group(s) of lymph nodes, and (4) extended radical neck dissection denotes removal of one or more additional lymphatic and/or nonlymphatic structure(s). Adherence to the principles of this classification system to describe neck dissection techniques should provide an improved method of communication. Furthermore, the system provides a rational framework on which subsequent terminology can be added.
Head and Neck Neoplasms↗
Concomitant chemotherapy-radiation therapy followed by hyperfractionated radiation therapy for advanced unresectable head and neck cancer.
In January 1988, we initiated a prospective study evaluating a new treatment approach with chemotherapy and radiotherapy for unresectable head and neck cancer. Weeks 1-4 were the initial debulking phase. Radiotherapy was delivered using 1.8 Gy/day to large portals including gross disease and all areas at risk. Cisplatinum, 100mg/m2, was given concomitant with radiotherapy on days 1 and 22. Weeks 5 and 6 were the boosting phase. This involved twice-a-day irradiation. The AM fraction of 1.8 Gy was given to the entire area at risk, whereas the PM dose of 1.6 Gy was limited to the gross disease alone. Thus a total of 70 Gy/6 weeks was delivered. A total of 24 patients were treated, 22 of whom have completed this protocol and are evaluable. All patients had massive disease, with 15 having gross involvement of brain, orbit, skull base, or carotid artery. Follow-up ranged from 3-22 months (median 12 months). Major responses were achieved in 96%, with 64% complete responses and 32% partial responses. Two patients with PR were able to undergo complete surgical resection, making the overall rate of complete response, including surgery, 73%. At 1 year, actuarial survival was 69%, and local progression-free survival was 56%. Distant metastases developed in 5 (23%). This approach appears both safe and effective in producing excellent regression and local control for far advanced head and neck cancer. More time is needed to see if these results are sustained. Efforts to build upon this experience appear warranted.
Adenocarcinoma↗
Prospective computer-assisted voice analysis for patients with early stage glottic cancer: a preliminary report of the functional result of laryngeal irradiation.
In January 1987 we began a prospective study aimed at evaluating objective parameters of vocal function for all patients treated with RT for early glottic cancer. All patients underwent vocal analysis using a voice analyzer interfaced with a computer. This allowed for the determination of percent voicing (%V) (normal = presence of phonation = 90-100%V). Other parameters such as breathiness (air turbulence or hoarseness) and strain (vocal cord tension) were also measured. Patients were recorded before RT, weekly during RT, and at set intervals after RT. There have been 25 patients studied. Eighteen (18) are evaluable at 9 months after treatment. All patients were male and ranged from 45-84 years old. Fourteen (14) and T1 lesions and received 66 GY/33 fractions to their larynx and 4 had T2 tumors and received 66-70 Gy/33-35 fractions. To date, all patients are locally controlled. Three distinct patterns of %V changes have been encountered. However, all patients demonstrated normal phonation pattern by 3 months after RT, and this is sustained at 9 months follow-up. In addition, 94% of patients have had significant decrease in breathiness after RT, which objectively documents diminished hoarseness. In 83%, breathiness is normal after RT. Most patients have had increased strain after RT, which documents increased vocal cord tension. However, strain remained within normal limits in 89%. Our preliminary analysis suggests that the majority of patients irradiated for early glottic cancer demonstrate a decrease in breathiness and an increase in strain after RT, and enjoy a resultant voice that has normal phonation maintained at 9 months after RT. Our data also demonstrate three distinct phonation patterns. Further follow-up will allow us to determine the prognostic significance, if any, of these patterns, and to continue to follow objective vocal parameters on larger numbers of patient.
Aged↗
Median sternotomy for cervical thorotrast granuloma and carotid hemorrhage.
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Aged↗
A management plan for tongue base cancer that includes brachytherapy.
For physiologic as well as oncologic reasons, there has been an increasing interest in radiation therapy as the primary treatment of base of tongue carcinoma. At Memorial Sloan-Kettering Cancer Center, we have used such a plan, using external beam conventional therapy in combination with an interstitial boost of iridium 192 to the primary site, plus planned neck dissections in selected patients. Between 1981 and 1986, 17 patients with untreated base of tongue squamous cell carcinoma were treated in this manner. Thirteen of the 17 are disease-free as a result of this therapy. Two patients have failed locally, yielding an actuarial local control of 87% at a median followup of 2 years. These data would suggest that primary radiation that includes interstitial therapy as part of the plan, along with neck dissection in certain situations, is a worthwhile method management of base of tongue carcinoma.
Adult↗
Vocal changes in patients undergoing radiation therapy for glottic carcinoma.
A prospective evaluation of vocal changes in patients receiving radiation therapy for T1 and T2 (AJC) glottic carcinoma was undertaken in January 1987. Vocal analysis was performed prior to radiotherapy and at specific intervals throughout the radiation treatment program. The voicing ratio was extrapolated from a sustained vowel phonation using the Visipitch interfaced with the IBM-PC. Preliminary observations suggested three distinct patterns of vocal behavior: 1. reduced voicing ratio with precipitous improvement within the course of treatment, 2. high initial voicing ratio with reduction secondary to radiation induced edema, with rapid improvement in the voicing component after the edema subsided, and 3. fluctuating voicing ratio during and following treatment. Enrollment of new patients and a 2-year follow-up of current patients was undertaken.
Aged↗
Filtering molecular dynamics trajectories to reveal low-frequency collective motions: phospholipase A2.
A novel method for analysing molecular dynamics trajectories has been developed, which filters out high frequencies using digital signal processing techniques and facilitates focusing on the low-frequency collective motions of proteins. These motions involve low energy slow motions, which lead to important biological phenomena such as domain closure and allosteric effects in enzymes. The filtering method treats each of the atomic trajectories obtained from the molecular dynamics simulation as a "signal". The trajectories of each of the atoms in the system (or any subset of interest) are Fourier transformed to the frequency domain, a filtering function is applied and then an inverse transformation back to the time domain yields the filtered trajectory. The filtering method has been used to study the dynamics of the enzyme phospholipase A2. In the filtered trajectory, all the high frequency bond and valence angle vibrations were eliminated, leaving only low-frequency motion, mainly fluctuations in torsions and conformational transitions. Analysis of this trajectory revealed interesting motions of the protein, including concerted movements of helices, and changes in shape of the active site cavity. Unlike normal mode analysis, which has been used to study the motion of proteins, this method does not require converged minimizations or diagonalization of a matrix of second derivatives. In addition, anharmonicity, multiple minima and conformational transitions are treated explicitly. Thus, the filtering method avoids most of the approximations implicit in other investigations of the dynamic behaviour of large systems.
Binding Sites↗
Brachytherapy as part of the definitive management of squamous cancer of the base of tongue.
Between 1981 and 1986, 17 patients were treated at the Department of Radiation Oncology at the Memorial Sloan-Kettering Cancer Center with squamous cancer of the base of the tongue whose definitive treatment included brachytherapy. The patient sample consisted of 14 men and 3 women with age range of 35 to 71 years (median = 58). There were four patients with T1 lesions, six with T2, six with T3, and one with T4. In general, treatment consisted of 5000-5400 cGy with external beam radiation and 2000-3000 cGy boost to the base of tongue via an Ir-192 implant using afterloading catheters. Necks were managed with elective radiation alone in the N0 group (n = 5) or with radiation plus neck dissection in the N+ group (n = 12). Five patients who would have required laryngectomy had they undergone primary surgery received neoadjuvant chemotherapy followed by external beam and implant as part of a larynx preservation study that was being done at our institution (4-T3, 1-T2). The range of follow-up is 8 to 59 months, with median follow-up of 24 months. No patients have been lost to follow-up. Crude local control by T-Stage are as follows: T1-4/4, T2-5/6, T3-5/6, T4-1/1. Actuarial local control at 24 months is 87%. There have been no neck failures. There have been five patients who had soft tissue ulceration (STU) and one patient who had osteoradionecrosis (ORN). All soft tissue ulceration patients have been successfully managed conservatively. The patient with osteoradionecrosis is currently being managed. In 4 of these 6 cases, the implant was the initial therapeutic intervention and the entire tumor bed was implanted. On the other hand, when external beam was the initial treatment, the boost was administered to the smaller volume of residual disease. Overall, 4 of 7 patients who had implant first developed either soft tissue ulceration or osteoradionecrosis, as opposed to 2 of 10 patients who had implant after external beam and/or chemotherapy. The numbers are too small to be statistically significant, but our current policy is to perform brachytherapy after the external beam. In addition, all those with either soft tissue ulceration or osteoradionecrosis were implanted with a non-looping technique. Overall, 6 of 12 patients treated with a non-looping technique developed an injury, whereas none of the five treated with a looping technique has developed one.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
Critical assessment of supraomohyoid neck dissection.
During a recent 5-year period, 115 patients had 131 supraomohyoid neck dissections. Eighty-one percent of these procedures were performed for squamous carcinoma. Seventy-nine percent of the primary tumors were located in the oral cavity and 16 percent arose in the oropharynx. Almost 80 percent of the necks dissected for primary squamous carcinoma were clinically N0, and occult nodal disease was discovered in 31 percent of these neck specimens. When the supraomohyoid neck dissection specimen showed no involvement, the overall incidence of treatment failure in the neck at 2-year follow-up was 5 percent. Almost all patients with occult squamous carcinoma in the supraomohyoid neck dissection specimen received postoperative radiotherapy, and the failure rate in the neck was 15 percent. When neck nodes were both clinically and pathologically involved, neck recurrence developed in 29 percent of the patients despite the addition of adequate postoperative radiotherapy. Among those patients with nonsquamous primary tumors and a pathologically negative supraomohyoid neck dissection specimen, there was only one subsequent treatment failure in the neck. Supraomohyoid neck dissection appears to be a valid staging procedure for clinically N0 patients with primary squamous carcinomas located in the oral cavity or oropharynx, with an appropriate yield of occult nodal disease, and infrequent treatment failure in the dissected neck when the supraomohyoid neck dissection specimen is pathologically uninvolved. When nodal disease is clinically obvious, treatment failure is more frequent, even with the addition of postoperative radiotherapy. The role of supraomohyoid neck dissection in this setting deserves further study.
Carcinoma, Squamous Cell↗
Ototoxicity of high-dose cisplatin by bolus administration in patients with advanced cancers and normal hearing.
Our institution undertook a phase I trial to define the toxicity of high-dose (150 to 225 mg) bolus administration (every 3 to 4 weeks) of cisplatin in patients with advanced cancers. All patients reported had baseline normal hearing. Hearing levels were measured prior to each course of chemotherapy. Audiological monitoring included conventional assessment of pure tone sensitivity at 500 to 8,000 Hz and assessment of ultra high frequencies (9,000 to 20,000 Hz). After one to two doses, 100% of patients failed to respond at 9,000 Hz and above. In the 2,000 to 8,000 Hz range, repeated administration of the drug effected successively lower frequencies with progressive loss, until a maximum threshold shift or plateau was reached at each frequency between 3,000 and 8,000 Hz. The plateau for cisplatin ototoxicity appears to fall within the moderate hearing loss range (40 to 60 dB HL) in the high frequencies. All patients complained of tinnitus and difficulty understanding speech in the presence of background noise. The pattern of pure tone audiometric alteration is consistent in all patients, all dosages, and each method of administration. The ultra high frequency alteration is prompt and dramatic.
Adult↗
New strategies for avoiding total laryngectomy in patients with head and neck cancer.
Cisplatin-based chemotherapy has yielded high response rates in patients with head and neck cancer but has failed to improve the survival rates in randomized studies. Thus, its place in the management of head and neck cancer remains unclear. We have been investigating whether the combination of chemotherapy and radical irradiation as an alternative to morbid surgery in selected patients might yield an improved quality of life without compromising survival. Between January 1983 and December 1985, we treated 32 patients with epidermoid carcinoma arising from the larynx, base of the tongue, or hypopharynx, using an interdisciplinary regimen, with the objective of avoiding total laryngectomy. All of these patients had large primary tumors that could not have been removed without total laryngectomy. Patients who could be treated by conservation laryngeal surgery were excluded, as were patients who presented with clearly unresectable disease. The regimen employed cisplatin-based chemotherapy together with brachytherapy and external radiation therapy, with highly individualized treatment planning. Seven patients had T2 lesions, 19 had T3, and 6 had T4. The follow-up periods ranged from 8 to 38 months (median, 18). The actuarial survival rate at 2 years is 85%, and the laryngectomy-free rate at 2 years is also 85%. None of the 11 patients with laryngeal cancer has relapsed, and none has required laryngectomy. None of the 12 patients with base of the tongue cancer treated by brachytherapy has relapsed above the clavicles and none has required laryngectomy, but 1 patient has died of complications of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗