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Biomedical subjects

G H Fletcher

Publications and source records attributed to G H Fletcher.

At least 37 records · Page 2Linked to original sources
PubMed1988

T1-T2 squamous cell carcinoma of the glottic larynx treated with radiation therapy: relationship of dose-fractionation factors to local control and complications.

This is an analysis of 304 patients with invasive, previously untreated T1-T2 squamous cell carcinoma of the glottic larynx treated with radiation therapy at the University of Florida between October 1964 and December 1984. All patients had a minimum 2-year follow-up and 82% had at least 5 years of follow-up. Patients were excluded from the analysis of local control if they died within 2 years of treatment with the primary site continuously disease-free; all patients were included in the analysis of treatment complications. Patients were staged according to the 1983 AJCC system. Stage T2 was subdivided into 2 groups as follows: T2a (normal mobility) and T2b (decreased mobility). The rates of local control with radiation therapy were as follows: T1, 159/171 (93%); T2a, 50/65 (77%); and T2b, 31/43 (72%). Patients were further divided into subsets based on T stage and the surgical procedure that would have been required to resect the lesion. Local control was noted to improve with higher doses and dose per fraction in 4 of 7 subsets. In 2 of 3 subsets where a dose-fractionation relationship was not observed, there were no local recurrences in 1 subset and only 2 local recurrences in the other. The overall incidence of serious complications was 5/304 (1.6%) and was associated with T stage and with increasing total dose and dose per fraction.

Carcinoma, Squamous Cell↗
PubMed1988

Radiation therapy for carcinoma of the nasal vestibule.

From 1963 to 1984, 32 patients with squamous cell carcinoma of the nasal vestibule received definitive radiation therapy. Of these, 11 patients whose superficial lesions were suitably located received radium implants, and the other 21 patients were treated with a combination of electron beam and 60Co. The implant doses ranged from 60 to 75 Gy and the external beam doses ranged from 55 to 70 Gy. In 12 patients, the submandibular and subdigastric nodes were electively treated with 60Co with doses of 45 to 50 Gy, and in 12 patients the strip of skin between the nose and the free border of the mandible was also electively irradiated. None of the 11 patients treated by interstitial implant experienced treatment failure. In the 21 patients treated by external beam, one patient had primary tumor recurrence and four patients failed in the unirradiated neck. A metastasis developed in the unrradiated tissues between the nose and the neck on the only patient who died of the disease. Necrosis of the anterior art of the upper jaw of one patient developed as a result of a hot spot. Today, when treatment is calculated with the help of a computer program and special techniques to optimize tumor dose, hot spots can be prevented.

Adult↗
PubMed1987

Behavioural evidence for the functionality of D-2 but not D-1 dopamine receptors at multiple brain sites in the 6-hydroxydopamine-lesioned rat.

Lisuride (D-2 agonist) and SKF 38393 (D-1 agonist) evoked characteristic circling and stereotyped orofacial movements when administered systemically or stereotaxically into the supersensitive caudate nucleus of unilaterally 6-hydroxydopamine-lesioned rats, which were respectively blocked by D-2 and D-1 antagonists. Lisuride induced similar behaviours from the accumbens, frontal cortex, pallidum, ventromedial thalamus, substantia nigra and periaqueductal grey, while SKF 38393 did not. Multiple brain sites may mediate D-2-induced (not D-1) behaviours following treatment with 6-hydroxydopamine.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1987

In morphinised rats SKF 38393 converts dopamine D2 receptor-mediated forward locomotion into backward walking.

The behavioural responses to RU 24213 (D2 agonist) and SKF 38393 (D1 agonist) were studied in the morphine cataleptic rat. D2 stimulation evoked slow forward walking coupled with head-down sniffing that was blocked both by SCH 23390 (D1 antagonist) and metoclopramide (D2 antagonist). D1 stimulation was without effect by itself, but when administered together with RU 24213 it reversed the direction of walking and initiated licking and chewing. Backward walking was attenuated by metoclopramide and restored to forward locomotion by SCH 23390. These data further show that D1 receptors exert an important modulatory influence on motor behaviours mediated by the D2 site.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1987

Topography of dopamine behaviours mediated by D1 and D2 receptors revealed by intrastriatal injection of SKF 38393, lisuride and apomorphine in rats with a unilateral 6-hydroxydopamine-induced lesion.

Stereotaxic injections of a dopamine D1 receptor agonist (SKF 38393) into different regions of the supersensitive striatum of rats with a unilateral 6-hydroxydopamine-induced lesion duplicated the systemic effects of the drug in a topographical manner. Although there was considerable overlap, it was possible to recognize discrete active zones or "hot-spots" giving rise to prominent sniffing, head movements and contralaterally directed circling, posture and grooming, both in the coronal plane and along the rostro-caudal axis. Two behaviours peculiar to D1 stimulation included contralateral forepaw myoclonus and forepaw nibbling, which paradoxically was directed mainly ipsilaterally. Each of the behavioural elements occurred independently of the others and after an inexplicably long latency. They were inhibited by the D1 antagonist SCH 23390, but not by the D2 blocking drug metoclopramide. Comparable circling responses were evoked by a D2 agonist (lisuride) injected into the neostriatum after a short delay, and instantaneously by apomorphine (D1/D2 agonist). Both drug behaviours originated diffusely from all parts of the denervated striatum with no obvious "hot-spots", except for circling which exhibited a bimodal distribution rostro-caudally. The actions of lisuride were blocked by systemic metoclopramide, but not by SCH 23390, while the actions of apomorphine were inhibited by both antagonists. Topographies of D2 receptor-mediated events were quite different from those encountered for D1 receptor stimulation by SKF 38393, though neither corresponded to the autoradiographic distribution of D1 and D2 binding sites in the intact striatum. These results reiterate the importance of D1 receptors in motor control and provide a basis for future investigations of the output pathways subserving D1-mediated behaviours.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1987

Role of the substantia nigra in the expression of dopamine D1 receptor-mediated and D2 receptor-mediated behaviours.

This study examines the proposal that striatonigral pathways support circling mediated by dopamine D1 receptors, but not D2 receptors, in unilaterally 6-hydroxydopamine-treated rats. In this model the D1/D2 agonist apomorphine, the D1 agonist 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine hydrochloride and the D2 agonists N-n-propyl-N-phenylethyl-P-(3-hydroxyphenyl) ethylamine hydrochloride, trans-(-)-4aR,4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo-(3, 4-g) quinolino monohydrochloride and lisuride evoked a characteristic spectrum of motor responses when administered systemically. In addition apomorphine, 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine hydrochloride and lisuride replicated their systemic effects following stereotaxic injection into the supersensitive caudate nucleus. Three months after injecting the pars reticulata of the dopamine-denervated nigra with kainic acid (1 microgram in 1 microliter), all motor responses to intracaudate dopamine agonists were reduced or abolished. Systemic responses were modified differentially, often as early as one day post-kainate. Contraversive circling and posturing were reduced, or even reversed (apomorphine only), grooming was attenuated (all drugs) and 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine hydrochloride-induced forepaw nibbling and dyskinesia were abolished. By contrast, sniffing, movements of the head and locomotion were either unaffected, or significantly potentiated, suggesting these components of behaviour arose from dopamine receptors outside the denervated striatum. These behavioural changes showed no signs of recovery three months after kainate, and were not produced by partial lesions of the reticulata (1 microgram kainate in 0.2 microliter). Contrary to earlier opinion our results indicate that the structural integrity of the substantia nigra pars reticulata is essential for the development of all forms of dopamine behaviour mediated by striatal D1 and D2 receptors, though not necessarily by dopamine receptors present at other locations.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1987

Results of irradiation in the squamous cell carcinomas of the anterior faucial pillar-retromolar trigone.

Between January 1966 and August 1981, 159 patients with previously untreated squamous cell carcinomas of the anterior faucial pillar or retromolar trigone received definitive radiation therapy at The University of Texas M. D. Anderson Hospital and Tumor Institute. All except 11 patients were treated by external radiation including combination of electron beams with high-energy photons or 60Co to doses ranging from 60 Gy to 75 Gy. In the N0 patients, as a rule, only the ipsilateral subdigastric nodes were treated electively to a dose of 50 Gy. The 5-year determinate survival rate for the overall group was 83%. The cumulative recurrence rate showed that 92% of the patients had recurrence by 2 years. Therefore, all patients except those who died with no evidence of local disease less than 2 years after treatment were evaluated for local control. The failure rate for the evaluable patients was 29% for T1 lesions, 30% for T2 lesions, 24% for T3 lesions, and 40% for T4 lesions. After salvage surgery, which consisted of intraoral resection in one-third of the patients and of a composite operation in the other two-thirds, the ultimate failure rate was 0% for T1 lesions, 6% for T2 lesions, 8% for T3 lesions, and 20% for T4 lesions. Whereas stage was a poor indicator for treatment outcome, there was a significantly higher failure rate for infiltrative and/or ulcerated lesions (35%) than for exophytic or superficial lesions (15%). Histologic grade was of no prognostic significance, nor was there any significant difference in the failure rate for lesions originating on the anterior faucial pillar versus that for lesions on the retromolar trigone. Following radiotherapy, 30% of the patients developed some degree of bone exposure but only 5.6% (9 patients) required a segmental mandibular resection. The probability of bone exposure was not dose related and more likely reflected tumor location on the mucoperiosteum. Of the whole group, 16 patients (10%) experienced a neck failure with 8 ultimate failures after salvage surgery. Among the 16 patients who had neck failures, 13 were originally staged N0; 6 of these patients had failures that occurred in the electively treated ipsilateral subdigastric area, but the field was too small to cover the nodes adequately. Aspects of the radiotherapy techniques with combined electron and photon beams that may influence the treatment outcome are discussed.

Carcinoma, Squamous Cell↗
PubMed1986

Guidelines for radiotherapeutic techniques for cervical metastases from an unknown primary.

Between 1968 and 1980, radiotherapy was part of the treatment of 120 patients with cervical nodes from an unknown primary tumor. Thirteen patients presented with supraclavicular nodes only and 14 presented with massive adenopathy; they are analyzed separately. The remaining 93 patients are analyzed in this report with emphasis on the applied radiotherapeutic techniques. Twenty of the 93 patients received radiation treatment to the neck only, 26 to the naso- and oropharynx and neck, and 47 to the naso-, oro-, and hypopharynx and neck. Fourteen patients subsequently developed a tumor at a primary site or a recurrence of metastases in the neck; in nine patients the disease recurrence was in areas that had not been irradiated. There was an increase in failures above the clavicles in patients who received irradiation to the neck alone. No correlation was found between initial tumor staging and subsequent failure, nor between types of surgical procedures and failure. In 86 of 93 (92.5%) patients there was eventual control of disease above the clavicles; 22 of the 93 patients died of disease, whereas 36 died of other causes. The determinate survival rate for the 93 patients treated with curative intent is 70% at 10 years. Guidelines for selection of techniques based on tumor and patient factors are discussed.

Adult↗
PubMed1986

Implications of the density of clonogenic infestation in radiotherapy.

Treatment schemes must be evaluated in a clinical context. It was observed by Coutard in the 1920s that exophytic tumors disappear by the third to fourth week of treatment and are more often controlled, stage for stage, than ulcerative and/or infiltrative tumors. It has also been demonstrated that the control rate is higher in patients whose tumor has clinically disappeared at the end of treatment than in those with clinically residual tumor. A possible explanation is that, after the clinical disappearance tumor cells that remain are euoxic during the latter part of treatment. Since some parameters, such as reoxygenation and proliferation, may work in opposite directions, a balance has to be found for each tumor mass. Furthermore, there are clinical facts that, although without explanation, must be considered.

Humans↗
PubMed1985

SKF 38393 and apomorphine modify locomotion and exploration in rats placed on a holeboard by separate actions at dopamine D-1 and D-2 receptors.

Horizontal motor activity, rearing and head dipping were recorded automatically in rats placed on a holeboard and taken as indices of locomotion and exploration. Other behaviours were assessed visually using a video camera. SKF 38393, 15-30 mg/kg (D-1 agonist), suppressed all three behavioural measures more effectively in habituated than in naive rats. These actions were blocked by SCH 23390 (0.05 mg/kg, D-1 antagonist) but not by haloperidol (0.05 mg/kg, D-2 antagonist). Apomorphine modified behaviour biphasically, causing haloperidol-resistant sedation at a low, presynaptic dose (0.05 mg/kg) and haloperidol-sensitive hyperactivity and stereotyped sniffing at a larger, postsynaptic dose (0.5 mg/kg, especially after habituation). Neither action was antagonised by SCH 23390. The results support the conclusion that D-1 and D-2 dopamine recognition sites can separately influence the processes controlling locomotion and exploratory activity in normal rats.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1985

Local regional effectiveness of surgery and radiation therapy in the treatment of breast cancer.

Although gross tumor can be controlled with high doses of radiation therapy, control is achieved at the expense of severe radiation sequelae. In order to improve tumor control with minimum complications, the field of treatment should contain only subclinical disease. This article reviews the successful combination of surgery for the removal of gross cancer and radiation of moderate dose for the treatment of subclinical disease in patients with breast cancer. In patients with clinically favorable and operable disease, the combination of a radical or modified radical mastectomy and postoperative radiation therapy of 5000 rad to the peripheral lymphatics and chest wall can secure 90% of the treated areas. For patients with locally and regionally advanced breast cancer, the combination of a simple mastectomy and dissection of the lateral axilla followed by postoperative irradiation of 5000 rad in 5 weeks to the chest wall, axilla, and peripheral lymphatic areas will control more than 85% of the patients treated as compared with approximately 70% control when surgery or radiotherapy alone is used, even with chemotherapy. Yet another clinical application of the subclinical disease concept is the successful combination of conservation surgery (whether segmental mastectomy, quadrantectomy, or wide excision) for gross tumor in the breast and axilla and irradiation for residual microscopic and multiple foci of tumor, yielding more than 90% control of locoregional disease with survival rates equal to those patients treated with radical or modified radical mastectomy. Results of multiple clinical trials and reported series are reviewed.

Antineoplastic Combined Chemotherapy Protocols↗