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Biomedical subjects

R Sessions

Publications and source records attributed to R Sessions.

12 recordsLinked to original sources
PubMed1995

Computer modelling of the alpha-helical coiled coil: packing of side-chains in the inner core.

In order to predict the structure of alpha-helical coiled-coil proteins from their sequences, it is necessary to know how the side-chains pack in the interface between the alpha-helical strands. Since in alpha-fibrous proteins leucine is the most common residue at both the a and d positions of the heptad repeat, which form the inner core of the interface, we determined the lowest-energy conformation for a two-stranded coiled-coil with the sequence (LAALAAA)5. Coiled-coils were constructed using the Crick equations with a range of pitches, major helical radii and relative rotations of the two strands, and with different starting side-chain conformations. On energy minimisation, convergence occurred to a small number of structures. The lowest-energy coiled-coil had 2-fold rotational symmetry, an average pitch of 131 A and an average radius of 4.52 A; the leucine side-chain conformations were tt and g+t at the a and d positions. This coiled-coil was used as a former to determine the lowest-energy side-chain conformations for the 63 combinations of a and d residues that occur in the repeating heptad sequence of rat skeletal myosin. The leucine residues at the a and d positions of the central heptad were replaced by the a-d pair of interest and molecular dynamics simulations performed to allow the side-chains of these residues to explore conformational space. The lowest-energy side-chain conformation of a residue at an a or d position depends on the nature of the partnering residue, consistent with the fact that these side-chains pack against one another. In most cases the lowest-energy structure was symmetric but in a few cases the side-chains were asymmetrically disposed in the two strands. The local pitch is very sensitive to the nature of the residues in the inner core and varies over a twofold range. In contrast, the radius and relative rotation of the two strands were relatively insensitive to sequence.

Alanine↗
PubMed1991

Larynx preservation with combined chemotherapy and radiation therapy in advanced but resectable head and neck cancer.

Forty patients with advanced, resectable squamous cell carcinoma of the larynx, oropharynx, or hypopharynx whose surgery would have required total laryngectomy (TL), were treated with one to three cycles of cisplatin-based chemotherapy before local therapy with the goal of larynx preservation. Clinical complete responses (CRs) or partial responses (PRs) to chemotherapy were seen in 26 of 40 patients (65%). Three patients with primary-site disease unresponsive to chemotherapy underwent resection of the primary lesion and neck dissection followed by radiation therapy (RT). Thirty-seven patients were referred after chemotherapy for RT +/- neck dissection. Thirty-one of 40 patient (78%) were rendered disease-free (no evidence of disease [NED]). With a median follow-up of 49 months (range, 31 to 76), the overall actuarial survival rate for the group was 58% at 2 years and 33% at 5 years. The failure-free survival rate was 42% and 33% at 2 and 5 years, respectively. Seven patients refused recommended TL throughout their course. This may have adversely affected survival results. A greater proportion of patients who achieved a CR or PR to chemotherapy remained disease-free compared with those who achieved less than a PR (P less than .001). Sixteen patients relapsed, 10 with locoregional disease. Six patients underwent TL, either for initial induction failure or at relapse, for an actual larynx-preservation rate of 34 of 40 patients (85%). If the seven patients who refused TL are included, the anticipated preservation rate is 27 of 40 patients (68%). Larynx preservation with combined chemotherapy and radiation is feasible and effective in patients with advanced, resectable squamous cell carcinoma of the head and neck (SCHN). This treatment approach requires a motivated patient, careful patient monitoring, and close interdisciplinary cooperation among oncologists.

Adult↗
PubMed1990

Impact of the time interval between surgery and postoperative radiation therapy on locoregional control in advanced head and neck cancer.

Between January 1975 and December 1980, 111 patients with AJCC stages III and IV squamous cell carcinoma of the head and neck were treated with surgery followed by planned postoperative radiation therapy. A previous analysis of a subgroup of these patients showed that, when radiation was delayed more than 6 weeks from surgery, a higher incidence of regional failure occurred compared with the incidence observed when therapy began within a 6 week period. We have looked back at this group of patients plus others in an attempt to determine whether other factors played a role in the results obtained. In the current study, 50 patients had a delay of 6 weeks or more and, of these, 11 (22%) suffered a locoregional recurrence. However, 8 of these 11 patients received suboptimal radiation doses (less than 56 Gy) for permanent control of the disease. In fact, of 17 patients who received at least 60 Gy and had more than a 6 week delay, only 2 (12%) had locoregional failure. This was similar to the incidence of failure in the patients who received at least 60 Gy and who started radiation within the first 6 weeks from surgery (3/20 [15%]). The effect of delay was apparent only in those who received less than 60 Gy (27% vs. 7%, P less than 0.05). Therefore, we cannot validate the previous conclusion that a greater than 6 week delay in the delivery of postoperative radiation therapy in advanced head and neck cancers produces poorer results. The current analysis suggests that a prolonged delay in postoperative radiation therapy in itself does not have a negative impact on locoregional control as long as appropriate tumorcidal doses of more than 60 Gy are employed.

Carcinoma, Squamous Cell↗
PubMed1989

The problem of neck relapse in early stage supraglottic larynx cancer.

We reviewed the records of 104 patients with Stage T1NO or Stage T2NO epidermoid carcinoma of the supraglottic larynx treated between 1965 and 1979. In 79 patients, surgery was the only type of initial treatment. These 79 patients are the subjects of this report. Forty-eight (61%) of these patients were treated by total laryngectomy, whereas 31 (39%) had a partial laryngectomy. An elective unilateral radical neck dissection was performed on 31 patients considered at high risk, but metastatic disease was found in the dissected side of the neck histologically in only 32% (ten of 31) of these patients. The minimum follow-up period was 5 years and the maximum was 20 years. Twenty-nine percent of the patients (23 of 79) experienced a neck relapse. The neck relapse rate was the same whether the patients did or did not have an elective radical neck dissection. Among the patients who experienced a neck relapse, 65% (15 of 32) have died of the cancer. Among those who did not experience a neck relapse, none (zero of 56) have died of the cancer (P less than 0.01). These results indicate that in surgically treated patients with early stage supraglottic larynx cancer, neck relapse was the major cause of failure associated with death from cancer. Strategies for decreasing the relapse rate are discussed.

Adult↗
PubMed1989

Percutaneous endoscopic gastrostomy and jejunostomy for long-term feeding in patients with cancer of the head and neck.

Enteral feeding is often required in patients with cancer of the head and neck. Percutaneous endoscopic gastrostomies (PEGs) and jejunostomies (PEJs) can facilitate enteral feeding in patients who require this treatment. The endoscopic technique allows for the placement of feeding gastrostomies and jejunostomies without a surgical procedure and eliminates the need for nasal tubes for long-term enteral feeding. Forty-two patients with head and neck tumors were referred for placement of PEGs because of severe dysphagia induced by tumors, surgery, radiation, or chemotherapy. The procedure was performed in the gastroenterology suite. Patients were sedated with intravenous meperidine and diazepam, and local anesthetic with lidocaine was applied to the area of incision. Average procedure time was approximately 20 minutes. The procedure was successful in 39 patients in whom tubes were placed ranging in diameter from 15F to 22F. PEGs were placed in 36 patients with intact stomachs and PEJs in three patients with previous gastrectomies. The remaining three procedures were unsuccessful because of technical reasons. There were three localized skin infections, and all responded to antibiotic therapy. Neither peritonitis nor any other immediate complication occurred. In 16 nonhospitalized patients, the procedure was performed on an outpatient basis. After a mean followup of 4.5 +/- 6 months of enteral feeding in the home, there was only one case of aspiration and subsequent pneumonia, and this case responded to antibiotics. No other long-term complications were noted. Thus feeding gastrostomies and jejunostomies can be placed safely and easily in patients with cancers of the head and neck by endoscopic methods without abdominal surgery. These tubes can be used for enteral feeding and eliminate the need for nasogastric tubes. They are better tolerated, are of a wider diameter, and have a reduced risk for migration, clogging, and aspiration-related complications.

Combined Modality Therapy↗
PubMed1987

Very-high-dose cisplatin with bleomycin infusion as initial treatment of advanced head and neck cancer.

Fifty-one patients with locally advanced squamous cancer of the head and neck (SCHN) were treated with up to three cycles of very-high-dose cisplatin, 187.5 mg/m2 (administered over five days) in hypertonic saline, and bleomycin infusion, 60 U/m2 (administered over five days), prior to definitive local therapy, in an attempt to improve complete remission (CR) and overall response rates. After chemotherapy, patients underwent surgery if the tumor was resectable for cure, (unless the operation involved total laryngectomy), and/or locoregional radiation therapy. Twelve patients (24%) achieved CR and 23 (45%) partial remission (PR) for an overall response rate of 69%. Thirty-nine of the 51 patients are evaluable following chemotherapy and locoregional treatment, and 28 (72%) have achieved disease-free status. Seven of these 28 (25%) have subsequently relapsed. Eleven of the 51 patients (22%) have died at median follow-up of 10+ months (3+ to 24+). Nausea and vomiting (94%) was the most severe acute toxicity. Myelosuppression was mild and nephrotoxicity was effectively prevented by the 3% saline diuresis. Bleomycin was withheld in 12 of 49 (24%) because of deterioration in pulmonary function tests. Ototoxicity in 12 of 49 (25%) and neurotoxicity in 19 of 49 (39%) were the most significant long-term toxicities. Very-high-dose cisplatin and bleomycin in this study was an effective chemotherapy regimen, but not more so than more conventional doses of cisplatin. Toxicity from both drugs was significant.

Adult↗
PubMed1985

A non-looping afterloading technique for base of tongue implants: results in the first 20 patients.

The results of treatment in the first 20 patients treated by a non-looping afterloading technique for base of tongue implant are described. Ten patients had carcinoma recurrent in the base of tongue after previous treatment and they were treated by implant alone. The other 10 patients had previously untreated carcinoma of the base of tongue and they were treated with a combination of interstitial implant, external radiation therapy and surgery. The minimum follow-up is 1 year and maximum 5 years. No local or regional failures have occurred in the previously untreated patients. No local failures have occurred in the previously treated patients who had lesions up to 4 cm in diameter, but three out of four patients with recurrent lesions larger than 4 cm have failed locally. Two patients developed necrosis related to the implant; the factors responsible for this are discussed.

Adenocarcinoma↗
PubMed1984

An on-line interactive interviewing program for epidemiological studies.

An on-line interactive verification and entry system (OLIVES) has been developed for conducting telephone interviews in large-scale epidemiological studies. Responses are automatically coded into a computer legible form suitable for analysis. Use of a question stack to control question flow allows on-line response modification, restart from any termination point, and minimal reprogramming in order to change question order. Numerical, coded, and text string data types are permitted. A multilevel hierarchical data structure reflects interview content. The advantages and disadvantages of the on-line approach are discussed. OLIVES is generalizable and is applicable to other on-line or off-line interview situations.

Child↗
PubMed1975

Therapeutic balloon occlusion of the inferior vena cava.

Thirty-five patients with venous thromboembolism and indication for inferior vena cava (IVC) interruption were treated by experimental balloon occlusion. Experience with this group resulted in the development of a method and equipment to allow transjugular obstruction of the IVC in the awake patient receiving anticoagulants. The study showed that the new method is atraumatic even when applied to sick patients, that it permits simultaneous treatment with anticoagulants and venous occlusion, and that long-term results (to more than four years) are excellent.

Adult↗