Radiation therapy for squamous cell carcinomas of the oral cavity and oropharynx: a review of recent techniques.
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Biomedical subjects
Publications and source records attributed to J F Wilson.
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Radiobiological evidence suggests that an improved therapeutic ratio might be achieved through the use of smaller than conventional dose fractions. The ultimate in small dose fractions for external beam radiotherapy would be fractionated low-dose-rate (LDR) irradiation, and clinical trials of fractionated external beam LDR therapy are already in progress. Using the BA1112 rat sarcoma, we have determined the 50% tumor control dose for LDR and for conventional-dose-rate (CDR) fractionated radiotherapy. These tumor control doses were compared to normal tissue tolerance doses for hemi-body irradiation in similar CDR and LDR schedules. Animals were treated 3 times per week without anesthesia using 10-19 fractions. LDR radiotherapy was done with 60Co at dose rates of 0.028-0.033 Gy/min; CDR radiotherapy was done with 250 kVp X rays at dose rates of 0.54-2.1 Gy/min. The tumor control dose modification factor (DMF) for LDR compared to CDR irradiation was 1.3 (1.0-1.5). For LDR and CDR hemi-body irradiation, the dose modification factor for 7 day lethality (gastrointestinal damage) was 1.7 (1.5-1.9), for 100 day morbidity was 1.8 (1.6-2.2), and for radiation nephritis at 90 days was 1.9 (1.7-2.3). The therapeutic gain factor for fractionated low-dose-rate irradiation compared to conventional-dose-rate fractionated radiotherapy was therefore 1.8/1.3 = 1.4 (1.2-1.8). The study shows that there is an experimental as well as a theoretical basis for anticipating a therapeutic benefit from the use of external beam fractionated LDR radiotherapy, and implies that the recognized therapeutic efficacy of brachytherapy is not due solely to the high localized dose.
Eating Attitudes Test (EAT) scores of forty female college students were compared to their electrodermal activity (EDA) responses when offered a plate of chocolate chip cookies. A significant positive correlation was detected between the EAT scores and the skin conductivity measures associated with the presentation of food. Women with the highest EAT scores also exhibited the greatest sympathetic nervous system responses to a plate of cookies. This finding supports the conclusion that the EAT is capable of identifying individuals who are preoccupied with food or anxious about eating.
This paper reports the results of a 10-year field trial designed to reduce the risk of infection by Echinococcus multilocularis to residents of a village in a hyperendemic area (Savoonga, St. Lawrence Island). The objective was to prevent dispersal of infective eggs of the cestode within the village by means of monthly treatments of dogs with praziquantel. Northern voles, Microtus oeconomus, present in the village as commensals, served as an index of risk, as the incidence of infection in the voles provides information about the availability of eggs within the confines of the inhabited area. Voles were examined annually during early June before the population of overwintering voles was diluted by the first annual litters. The pretreatment infection-rate within the village was 29% (range 22-35%), and in control areas at some distance from the village for the entire study period it averaged 53% (284 infected voles from a sample of 533). Some fluctuation in incidence of infection in village voles occurred, apparently depending on the extent to which the residents kept their dogs chained and thus available for treatment. The success of the programme was demonstrated by the reduction in prevalence of infection to about 1% of voles in 1985, and an average infection rate during the last five years of the study of 5% (29 infected voles in a sample of 582). This 83% average reduction in the prevalence of the larval cestode within the village reflects a corresponding reduction in the risk of acquiring by the residents of the village. The method would be applicable for the control of E. multilocularis in most hyperendemic regions. Success depends, however, on elimination of unrestrained dogs and a precise schedule of treatment.
The accuracy and precision of drug measurements made by different analytical techniques of a range of eight antiepileptic drugs, four tricyclic antidepressants, theophylline, and digoxin in three different matrices, human, bovine, and newborn calf serum, were compared using data reported to the Heathcontrol External Quality Assurance Scheme over 18 months. Neither of the animal serum samples was universally satisfactory compared with human serum. The newborn calf serum sample produced results that were closer to the spiked drug concentrations than those in bovine serum for most of the analytes covered by the survey. Both animal samples were unsuitable for digoxin, for which the use of scarce human material is recommended.
An external quality assessment survey of testing facilities in UK clinical laboratories for the detection of drugs of abuse was made with nine freeze-dried samples of urine containing representative drugs with their metabolites from the following seven classes; amphetamines and stimulants, barbiturates, cannabinoids, cocaine, minor tranquillisers, opiates and non-opiate narcotics. Reports were received from 120 laboratories. Thirty six per cent of laboratories reported on all seven drug classes and 71% on the five classes excluding cannabinoids and cocaine. A single drug screening technique was used by 32% of laboratories whilst 46% were able to perform tests by both immunological and chromatographic techniques. There was a mean level of false positive reporting of 4.3% and an observed level of false negative reports of 8.4%, the latter underestimating the true frequency. The minor tranquillisers, cocaine and benzoyl ecgonine were the most frequently missed analytes. Several false reports had important potential implications for patient care.
The understanding of psychiatric morbidity in the infertile population relies to a great extent upon the instruments used to measure psychopathology. The present study investigated the distinction between psychiatric morbidity and infertility strain reactions in a sample of 104 infertile couples using the SCL-90-R. Some symptoms ordinarily indicative of psychopathology can represent normal side effects or reactions to infertility treatment, thus causing spurious estimates of pathology. Alternately, item analyses revealed a profile of infertility strain reflecting tension, depressive symptoms, worry, and interpersonal alienation frequently occurring among both male and female infertility patients. The concept of infertility strain is suggested as a vehicle for understanding the functioning of infertile patients and to circumvent the stigmatizing effects of psychiatric labels while providing appropriate intervention.
Release of alpha-melanocyte-stimulating hormone (alpha-MSH) from frontal slices of rat hypothalamus superfused with oxygenated artificial cerebrospinal fluid (ACSF) was quantified by radioimmunoassay. Control depolarisations with 50 mM KCl-containing ACSF produced significant increases in alpha-MSH release which were partially blocked by 10(-6) M cinanserin, a serotonin (5-HT) receptor antagonist. Superfusion of the tissues with varying concentrations of 5-HT (10(-7) M to 10(-4) M) resulted in an inverted U-shaped dose-response curve, maximum alpha-MSH release being obtained with 10(-6) M 5-HT. Addition of 10(-6) M cinanserin shifted the 5-HT dose-response curve to the right whilst the presence of 10(-8) M flupenthixol, a dopamine receptor antagonist, resulted in a sigmoidal 5-HT dose-response curve. Superfusion with ACSF containing either 10(-7) M fluoxetine, a 5-HT re-uptake inhibitor, or 10(-7) M p-chloroamphetamine, an agent releasing 5-HT, induced significant increases in alpha-MSH release which were abolished in the presence of 10(-6) M cinanserin. These data demonstrate the presence of an endogenous 5-HT system that exerts a biphasic effect on alpha-MSH release. A stimulatory effect caused by lower 5-HT concentrations appears to be a direct action whilst an inhibitory effect at higher concentrations is mediated through an inhibitory endogenous dopaminergic system. A significant proportion of K+-stimulated peptide release is 5-HT-mediated.
Forty-one patients with epithelial malignancies of the ovary treated at the Medical College of Wisconsin Affiliated Hospitals from 1976 to 1984 had paraffin embedded tissue available for review. Of the 41 patients, 40 had adequate material to provide 50 micron sections that were evaluated with flow cytometry to determine DNA content. Tumor- and patient-related parameters were then correlated with the results of flow cytometry. Overall survival at 5 years in these patients was 43%, and relapse-free survival was 50%. Forty percent of the tumors were diploid, and 60% were aneuploid. Five-year survival for diploid patients was 74% with a relapse-free survival of 71%. Corresponding overall and relapse-free survivals for aneuploid patients were 22% and 35%, respectively. Distribution of the patients by histology, stage, and grade was equal between the diploid and aneuploid groups. All patients were treated with whole abdominal plus concomitant pelvic boost irradiation; total doses to the whole abdomen ranged from 10 Gy to 46 Gy (1000 to 4600 cGy) with the median dose being 37.5 Gy. Approximately 40% of the patients received chemotherapy, which usually consisted of a single agent (Alkeran, Burroughs Welcome, Research Triangle Park, NC). This retrospective study of patients with ovarian cancer treated with radiation therapy suggests the possibility that determinations of DNA ploidy may be useful in selecting patients whose poor prognosis dictates that a more aggressive therapy be used.
Release of alpha-melanocyte-stimulating hormone (alpha-MSH) from slices of rat hypothalamus superfused with artificial cerebro-spinal fluid (ACSF) was quantified by radioimmunoassay. Addition of 10(-6) M quinpirole, a D2-dopamine receptor agonist, to the superfusion medium caused a significant (P less than 0.001) reduction in the amount of alpha-MSH released upon depolarisation with 50 mM potassium from 319 +/- 37% to 110 +/- 16% of basal release in normal ACSF (mean +/- S.E.M.). Basal peptide release in the presence of quinpirole was unaffected. Sulpiride, a D2-dopamine receptor antagonist, at a concentration of 10(-6) M, induced a significant (P less than 0.05) increase of both basal and potassium-stimulated alpha-MSH release to 203 +/- 21% and 447 +/- 88% of basal release in normal ACSF respectively. The latter increases were abolished when sulpiride and quinpirole were added in combination. SK&F 38393-A and SCH 23390, a D1-dopamine agonist and antagonist respectively, had no significant effect on either basal or potassium-stimulated alpha-MSH release. It is proposed that endogenous dopamine exerts an inhibitory control on alpha-MSH release from the rat hypothalamus via D2-dopamine receptors and that in isolated hypothalamic slices there is a tonic inhibition of peptide release due to the activity of this system.
The Medical College of Wisconsin implemented a major bone marrow transplant (BMT) program in July 1985. The type of transplants to be focused on were allogeneic T-lymphocyte deplete. Total body irradiation (TBI) was initially patterned after the Memorial method. Patients received total body irradiation in a sitting position at a dose rate of 20-25 cGy/minute with 50% attenuation lung blocks used both anterior/posterior and posterior/anterior. Electron boosting was utilized for the ribs beneath the lung blocks. Occasionally, lower extremity boosting was required because of the sitting position. A dose of 14 Gy was chosen since T-lymphocyte deplete bone marrow transplant data suggest the need for higher total doses to consistently obtain engraftment. This dose was given in 3 equal daily fractions over 3 days following conditioning chemotherapy. Six of 11 patients treated in this manner developed lethal pulmonary events. In response to the pulmonary toxicity, partial lung shielding was increased to 60% attenuation. In the next 107 patients receiving this program of total body irradiation there was a reduced incidence of fatal pulmonary events (10 cases of fatal idiopathic interstitial pneumonitis and 12 cases of fatal pulmonary infections) after a median follow-up of 9 months. This was an obvious improvement over the initial group. A significant level of hepato-renal toxicity was also observed with 14 Gy total body irradiation when no liver or kidney blocking was used. Of the first 20 patients treated, three cases of fatal veno-occlusive disease resulted. Subsequently, a 10% attenuation right sided liver block was added. Five of 98 patients treated with this block have developed fatal hepatic dysfunction, (median follow-up of 7.2 months). This incidence is not statistically different from the initial group but favors the use of the liver block. Some renal toxicity was also detected with the earlier regimen, especially in pediatric patients. Partial kidney blocking has been implemented to minimize this toxicity. Our current dose rate has been reduced to 8 cGy/minute in a further attempt to reduce organ toxicity. To date, this selective blocking has not adversely affected the excellent rate (96%) of first time engraftments.
Treatment principles for extrapulmonary small cell undifferentiated carcinoma follow those established for primary lung presentations including systemic chemotherapy and prophylactic cranial irradiation. Radiation of carcinoma involving the maxillary sinus includes lateral and anterior portals which exit through the brain. Presented is a treatment strategy used for postoperative radiation of small cell undifferentiated carcinoma of the maxillary sinus in conjunction with prophylactic cranial irradiation. Specifics of dosimetry include achievement of 55 to 60 Gy within the tumor volume of the maxillary sinus, while achieving homogeneity of dose (30 Gy) within the cranial contents. Application of the described technique to analogous clinical presentations is also discussed.
Using computerized tomography (CT) in which cardiac anatomy was defined, doses delivered to the cardiac compartments, vascular and conduction systems were assessed for various standard techniques of primary breast irradiation. Included in the analysis were 6 MV photon tangents (T) alone, or in conjunction with a separate internal mammary field (IMF). Beams evaluated in the IMF were 6 MV photons, 12 MeV electron beam, and mixed photon/electron beam; Cobalt 60 was also analyzed as an alternate photon beam. Treatment of the IMF with photons, either alone or in combination with electron beam, delivered doses ranging between 30 Gy to 50 Gy to all chambers of the heart, coronary arteries and branches of the conduction system. Complete sparing of the posterior cardiac structures and volume is accomplished with treatment plans using tangents alone or in combination with 12 MeV electron beam irradiation to the IMF. Sparing of the anterior wall of the left ventricle, Bundle of His and left anterior descending coronary artery is also achieved in treatment with tangents and 12 MeV electron beam IMF. Doses to this region with tangents alone ranged from 20 Gy to 45 Gy compared to 0 to 30 Gy with tangents and 12 MeV electron beam IMF. Clinical significance of these findings will be discussed.
Sinusitis is a common problem that is routinely diagnosed and treated by most primary care physicians. Although most cases usually respond to appropriate therapy, some occasionally progress to the development of intracranial complications, including meningitis, osteomyelitis, epidural and subdural empyema, intracranial mucocele or polyps, and frank brain abscess. It is important to develop a rational approach to the diagnosis and treatment of these conditions. A high clinical index of suspicion must always be maintained, since symptoms are often masked by previous antibiotic therapy. Radiologic evaluation must always include computerized tomography (CT) for accurate diagnosis and surgical planning. Therapy includes surgical drainage and high doses of appropriate intravenous antibiotics. Cefuroxime and metronidazole provide excellent broad spectrum antibacterial coverage. Only early recognition and appropriate therapy can reduce the potential morbidity and mortality associated with these life-threatening complications.
The accuracy and precision of eight techniques used to measure a range of eight antiepileptic drugs in human serum were compared using data from 80 samples from the Heathcontrol External Quality Assurance scheme. The fluorescence polarization immunoassay was significantly more precise than other techniques for several analytes, producing the lowest number of measurements rejected as outliers and measurements with the lowest coefficient of variation. Other techniques had a significantly lower precision. Nephelometry (Neph) produced most outliers for phenytoin and carbamazepine and had the highest variability for phenytoin. Gas-liquid chromatography (GLC) with derivatization was most variable for phenobarbitone and primidone. Measurements by GLC with or without derivatization contained greater than 10% of outliers and were least precise for carbamazepine. Differences between the majority of techniques were in many cases, however, not significant. The accuracy of techniques was assessed from differences between sample means and spiked drug concentrations. Neph was notable in producing overestimates at lower concentrations. Immunoassay methods had a 16-21% cross-reactivity with carbamazepine 10,11-epoxide when measuring carbamazepine. All techniques reported underestimates for valproic acid that were thought to result from the hygroscopic nature of the salt used for spiking.
Comparison of the precision and accuracy of measurements made between December 1979 and January 1988 of tricyclic antidepressant drug concentrations in freeze-dried external quality-assurance samples of human serum showed only occasional significant differences between the different chromatographic techniques used for drug assay. Larger differences between data collected in different years correlated with changes in the source of the sample matrix and the personnel responsible for sample preparation. Measurements of amitriptyline and imipramine were more precise than those of nortriptyline and desipramine; the mean coefficients of variation of measurements were 20.2, 19.6, 26.6 and 25.3%, respectively. The data indicate the need for further interlaboratory studies directed at reducing the high level of variability in tricyclic measurements.
Acute epiglottitis is a life-threatening infection of the supraglottic airway that can occur at any age. Although it is traditionally described as a childhood infection, recent reports describe an increased recognition of this problem in adults. When appropriate and timely therapy is instituted, this condition is generally self-limited. Recurrent acute epiglottitis is exceedingly uncommon, and its treatment rarely is addressed. We encountered and treated a case of recurrent acute epiglottitis in an adult. After the third recurrence, careful consideration was given to possible pathophysiologic mechanisms and potential therapeutic options. Further recurrence was prevented effectively by performing a lingual tonsillectomy. Although this is an unusual condition, the cause of recurrent acute epiglottitis may be related to chronic lingual tonsillitis. Lingual tonsillectomy in these cases may help prevent further recurrent episodes.