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Biomedical subjects

L J Peters

Publications and source records attributed to L J Peters.

At least 37 records · Page 2Linked to original sources

Positron emission tomography (PET): experience with a large-field-of-view three-dimensional PET scanner.

Positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (FDG) is an accurate technique for staging and therapeutic monitoring in oncology. We evaluated our use of FDG PET in an oncology centre after our first 2500 studies, and summarise our experience of PET for the major referral indications. Optimised for clinical service, PET offers lower scanning costs and therefore improved cost-effectiveness.

Cost-Benefit Analysis↗

Apoptosis and the Bcl-2 gene family -- patterns of expression and prognostic value in stage I and II follicular center lymphoma.

PURPOSE: The prognostic significance of spontaneous levels of apoptosis and Bcl-2, Bax, and Bcl-x protein expression in follicular center lymphoma (FCL) is unknown. The objectives of this retrospective study were (1) to investigate the relationship between pretreatment apoptosis levels and long-term treatment outcome in patients with Stage I and II FCL; (2) to define the incidence and patterns of Bax and Bcl-x protein expression in human FC; and (3) to determine the relationship of Bcl-2, Bax, and Bcl-x expression with spontaneous apoptosis levels and clinical outcome in localized FCL. METHODS AND MATERIALS: Between 1974 and 1988, 144 patients with Stage I or II FCL were treated. Hematoxylin and eosin (H & E) stained tissue sections of pretreatment specimens were retrieved for 96 patients. Treatment consisted of regional radiation therapy (XRT) for 25 patients, combined modality therapy (CMT) consisting of combination chemotherapy and XRT for 57 patients, and other treatments for 14 patients. Median follow-up for living patients was nearly 12 years. The apoptotic index (AI) was calculated by dividing the number of apoptotic cells by the total number of cells counted and multiplying by 100. Expression of Bcl-2, Bax, and Bcl-x proteins was assessed using immunohistochemistry. RESULTS: The mean and median AI values for the entire group were 0.53 and 0.4, respectively (range: 0-5.2). The AI strongly correlated with cytologic grade, with mean AI values of 0.25 for grade 1, 0.56 for grade 2, and 0.84 for grade 3 (p < 0.0005; Kendall correlation). A positive correlation was present between grouped AI and grouped mitotic index (MI) (p = 0.014). For patients treated with CMT, an AI < 0.4 correlated with improved freedom from relapse (FFR) p = 0.0145) and overall survival (OS) (p = 0.0081). An AI < 0.4 did not correlate with clinical outcome for the entire cohort or for patients receiving XRT only. Staining of tumor follicles for the Bcl-2 protein was positive, variable, and negative in 73%, 15%, and 12% of cases, respectively. Positive staining of tumor follicles was observed in 96% of cases for both the Bax and Bcl-x proteins. Expression of Bcl-2, Bax, or Bcl-x did not correlate with AI or clinical outcome. CONCLUSION: The level of spontaneous apoptosis in pretreatment specimens correlates with cytologic grade of FCL and is a significant predictor of FFR and OS for patients with localized FCL receiving CMT.

Analysis of Variance↗

Planned neck dissection as an adjunct to the management of patients with advanced neck disease treated with definitive radiotherapy: for some or for all?

BACKGROUND: Management of patients with head and neck carcinoma and advanced nodal disease is controversial. The purpose of this analysis was to evaluate the efficacy and toxicity of definitive radiotherapy followed by planned neck dissection in patients with bulky neck disease. MATERIALS AND METHODS: The records of 52 patients who were treated between 1989 and 1995 at the Peter MacCallum Cancer Institute with a planned neck dissection after radical radiotherapy were reviewed. All had advanced neck disease with one or more nodes >/=3 cm in maximum diameter, 94% being staged N2-3. The most common primary site was the oropharynx (56%). Sixty percent of patients had either T2 or T3 primaries and all were AJCC stage IV. Treatment consisted of high-dose radiotherapy to the primary and involved neck sites using various fractionation protocols followed by radical or modified radical neck dissection after confirmation of a complete response at the primary site. The median follow-up for living patients was 58 months (range 32-97). RESULTS: There were nine regional failures, of which three were outside the dissected neck, yielding a 5-year actuarial overall neck control rate of 83% and an in-field control rate of 88%. In-field control rates by neck stage were N1 3/3; N2 31/35; N3 11/13 and NX 1/1. There was only one in-field failure among 28 patients who had pathologically negative neck specimens compared with five in 24 patients with morphologic evidence of residual disease. Of the 24 patients with pathologically positive necks, 5 were long-term survivors and were probably cured by their surgery. Another 4 died of intercurrent disease without documented recurrence of their head and neck cancer. Ten patients recurred at their primary sites (5-year actuarial control 79%) and 8 developed distant metastases (5-year actuarial rate 20%). A total of 21 patients failed at one or more sites and none was salvaged. Five-year actuarial disease-free survival was 57% and overall survival 38%. Nine patients (17%) sustained significant complications following neck dissection. CONCLUSIONS: In patients with advanced neck disease who are treated primarily with radical radiotherapy, planned neck dissection provides excellent regional control and appears to cure a subset of patients. However, routine neck dissection adds significant morbidity to treatment and should ideally be avoided in those patients in whom surgery is either unnecessary (no residual tumor) or futile (unsalvageable disease recurrence outside the dissected neck). Based on our analysis and other recently reported series, we now recommend observing patients who have a complete response to high-dose radiotherapy (+/- chemotherapy). The ability of PET imaging to detect residual viable tumor in the head and neck or at distant sites is under investigation.

Adult↗

Do acute mucosal reactions lead to consequential late reactions in patients with head and neck cancer?

BACKGROUND AND PURPOSE: The relationship between acute and late mucosal reactions remains ill defined but is of considerable relevance to efforts to produce therapeutic gains through the use of altered fractionation schemes and concurrent chemotherapy. We therefore investigated whether acute mucosal reactions in patients treated with an accelerated and a conventionally fractionated radiotherapy regime predicted the severity of late mucosal reactions. PATIENTS AND METHODS: The study population consisted of 191 patients randomised on a prospective trial comparing conventional fractionation at 2 Gy/fraction per day, 70 Gy over 47 days with an accelerated regimen of 59.4 Gy, 1.8 Gy b.i.d over 24 days for Stage III-IV carcinoma of the head and neck. Acute and late mucosal reactions were scored according to RTOG/EORTC criteria and analyzed using multiple regression techniques. RESULTS: The duration of time spent by patients at the acute confluent mucositis grade 3 level was inversely related to the time to onset of the reaction for both fractionation schedules. Time to onset was more rapid for patients treated on the accelerated schedule but time spent at the reaction grade did not differ significantly between the schedules. After correction for treatment and patient related factors, anatomical site (oral cavity/oropharynx versus hypopharynx/larynx) and increasing duration of confluent mucositis emerged as independent predictors of the hazard of late mucosal reactions with the latter effect being more pronounced in the accelerated treatment arm. The expected reduction in late mucosal effects in the accelerated fractionation arm, predicted by the LQ model for late effects was identified only in patients whose acute confluent mucosal reactions lasted less than 20 days. CONCLUSIONS: The presence of individual patient susceptibility factors that determine the severity of acute mucosal reactions is suggested. A link between severe and prolonged acute reactions and the risk of developing late mucosal reactions that is independent of biological dose, has also been found. Purpose designed prospective studies of these issues are necessary.

Acute Disease↗

Postprandial response of jejunal slow waves and mediation via cholinergic mechanism.

The postprandial characteristics of jejunal myoelectrical activity and its mediation via cholinergic nerves were investigated in this study. Four pairs of bipolar electrodes were implanted on the serosa of the proximal jejunum of nine female hound dogs (14-22 kg). In the control session, the recording of jejunal myoelectrical activity was made for 30 min in the fasting state and for 90 min after a solid meal (0.45 kg, 838 kcal). The study session followed the same protocol except that a bolus of 0.25 mg/kg atropine was injected intravenously 30 min after the meal. Computerized spectral analysis was performed to calculate the frequency, power, and percentage of 17-22 cycles/min (cpm) slow waves. A special artificial neural network program was applied to compute the spike bursts superimposed on slow waves. All data were expressed as mean +/- SE. The postprandial frequency of the jejunal slow waves was significantly increased from 18.42 +/- 0.28 cpm in the fasting state to 18.95 +/- 0.22, 19.28 +/-0.23, and 19.28 +/- 0.22 cpm during the first, second, and third 30-min periods after the meal (all P < 0.03 in comparison with the fasting state). The percentage of the slow waves superimposed with spike bursts was increased from 19.33 +/- 3.90% at fasting state to 35.16 +/-2.76%, 32.87 +/- 4.06%, and 34.88 +/- 3.51% during the first, second, and third 30-min periods after the meal (all P < 0.03 in comparison with fasting state). Atropine abolished the postprandial increases in the frequency of slow waves and the number of spike bursts. No significant postprandial changes in the power and the percentage of 17-22 cpm slow waves were observed. In conclusion, the postprandial response of the jejunal slow waves after a solid meal presents as an increase of the frequency of slow waves and the number of the spike bursts which can be abolished by atropine, and the postprandial response of the jejunal slow waves is a neural reflex dominantly mediated via vagal cholinergic nerves.

Animals↗

Effects of electroacupuncture on gastric migrating myoelectrical complex in dogs.

The aim-of this study was to investigate the characteristics of the gastric slow wave during different phases of the migrating myoelectrical complex (MMC) and the effect of electroacupuncture on the MMC. The experiment was performed in eight hound dogs implanted with one pair of bipolar serosal electrodes 2 cm proximal to the pylorus. Gastric myoelectrical activity was recorded for three complete cycles of the MMC in two sessions, one with electroacupuncture at points ST36 and PC6 and the other at sham points. The acupuncture was performed for 30 min in phase I of the second cycle of the MMC. Spectral analysis was performed to compute the frequency and power (amplitude) of the gastric slow wave, whereas blind visual analysis was applied to compute the appearance of spike potentials and the length of each phase of the MMC. It was found that there was a significant difference in the frequency and power of the gastric slow wave during different phases of the MMC (P < 0.05). Phase I was characterized with the highest frequency and lowest power of the gastric slow wave, whereas phase III exhibited the highest power in the slow wave. It was also found that in comparison with the sham points, electroacupuncture at the acupoints increased the number of spike bursts. This increase was not significant during the MMC cycle with electroacupuncture (34.4+/-4.1 vs 27.5+/-2.5%, P > 0.05) but became significant during the cycle after electroacupuncture (39.8+/-3.3% vs 27.5+/-2.5%, P < 0.0005). Similarly, during the MMC cycle after electroacupuncture at the acupoints, there was a significant decrease in the length of phase I (14.8+/-2.2 vs 46.9+/-6.1 min, P < 0.003) and a significant increase in the length of phase II (75.6+/-9.9 vs 30.6+/-4.1 min, P < 0.003) and phase III (25.8+/-0.6 vs 22.1+/-0.7 min, P < 0.003). A similar increase was observed during the MMC cycle with electroacupuncture but was not statistically significant. In conclusion, the gastric slow wave has the highest power during phase III of the MMC, indicating that the antral contraction is characterized not only by the appearance of spikes, but also by the increased power of the slow wave. Electroacupuncture at acupoints of ST36 and PC6 enhances the gastric MMC by reducing the length of phase I and increasing the length of phases II and III.

Acupuncture Points↗

Comparison of effects on colonic motility and stool characteristics associated with feeding olestra and wheat bran to ambulatory mini-pigs.

The goal of this study was to compare the stool-softening effects of olestra and wheat bran and to determine if changes in patterns of propagating colonic motility were associated with the observed stool softening. Mini-pigs were fed chow (control) or chow supplemented with olestra (80 g/day) or wheat bran (80 g/day) for four days. Proximal colonic motility was monitored continuously, stool viscosity and fecal output measured daily, and cecal-to-anal transit time determined. Compared to controls, olestra and wheat bran significantly softened stool but had no effect on fecal wet weight or colonic transit time. Neither olestra nor wheat bran changed the number of propagating contractions per day, amplitude, motility index, propagation velocity, or the relative distribution of fast and slow propagating contractions. Our data suggest that the stool-softening effects of olestra and wheat bran are not due to direct stimulation of propagating contractions in the colon of the mini-pig.

Animals↗

A usability evaluation for telemedicine medical equipment.

This paper describes a conceptual framework and human factors evaluation for usability assessment of commercially available telemedicine technology. Four criteria of human factors evaluation are utilized: (1) technical acceptability; (2) operational effectiveness; (3) clinical appropriateness; and (4) equipment selection. These criteria were applied to commercially available video-otoscope systems for otological evaluations.

Equipment Design↗

Overview of telemedicine applications for otolaryngology.

OBJECTIVE/HYPOTHESIS: As we evolve into the managed care era, telemedicine technologies can help to provide efficiencies for the entire health care system. Our practice is centered around a residency training program in a federal facility. Our goal was to lay the groundwork for an entire service being on-line. STUDY DESIGN: Prospective. METHODS: The stepwise process is as follows: needs assessment to examine what part of the practice would lend itself to telemedicine deployment; usability studies to select the best equipment; study in-house to normalize the technology to the current standard of care comparing control subjects with experimental subjects; and deploying remote units to study remote referral. RESULTS: Video-otoscopy captures the image of an eardrum that can be sent from a remote site in a store-forward mode. After normalizing the standard of care, the potential for diagnosing and treating certain ear conditions such as hearing loss is readily apparent. An audiogram, pertinent laboratory data, and history and physical performed by the referring primary care provider would allow the patient to be seen and triaged virtually. Time savings for the patient and the otolaryngologist would be gained. Initial data indicate a greater than 90% correlation with handheld otoscopy and binocular microscopy. In speech sciences, a need existed to evaluate and treat patients from remote sites where speech therapists are unavailable. The use of live video teleconferencing to evaluate and treat patients in-house has preliminary results that show no difference in outcomes. Studying the proctoring of remote surgeons is also a need, as one of our military missions. Initial data show no difference in outcomes when residents are proctored by attending physicians from a physically separated control room in the hospital. We also participate with the Internet Tumor Board, which links four remote sites with our medical center. Different sites scroll through the slides that are listed on a Web site while linking each site with audio teleconferencing. We are initiating Internet Grand Rounds using the same technology. CONCLUSION: These efforts performed in a stepwise approach will lead to an otolaryngology--head and neck surgery service that is on-line for the next millennium, with telemedicine advances normalized to the standard of care.

Hawaii↗

Phase I/II trial of radiation with chemotherapy "boost" for advanced squamous cell carcinomas of the head and neck: toxicities and responses.

PURPOSE: Extrapolating from our experience delivering a "boost" field of radiation concurrently with fields treating both gross and subclinical disease at the end of a course of radiation therapy, we developed a regimen to deliver concurrent chemotherapy during the last 2 weeks of a conventionally fractionated course of radiation. PATIENTS AND METHODS: Patients had stage III or IV biopsy-proven squamous cell carcinoma originating from a head and neck mucosal site. The regimen was 70 Gy delivered over 7 weeks with concurrent fluorouracil (5-FU) and cisplatin given daily with each radiation dose during the last 2 weeks. A phase I study was performed to determine the maximum-tolerated dose (MTD) before a phase II study was conducted. RESULTS: The MTD was 400 mg/m(2) per day for 5-FU and 10 mg/m(2) per day for cisplatin. Mucositis persisting more than 6 weeks after therapy was the dose-limiting toxicity. A total of 60 patients were treated on the two phases of the study. Eighteen patients (35%) treated at the MTD developed prolonged mucositis. There were two cases of neutropenic sepsis, including one fatality. The actuarial 2-year rates for overall survival, freedom from relapse, and local control were 62%, 59%, and 80%, respectively. CONCLUSION: Preliminary locoregional control rates seem to be higher than those reported for treatment with radiation alone. Toxicity was also greater than that seen with radiation alone, but the regimen was designed to deliver an intense treatment schedule, which could be completed without significant interruptions, and to obtain high control rates above the clavicles. These end points were achieved.

Actuarial Analysis↗

Non-metastatic Ewing's sarcoma: twenty years of experience suggests that surgery is a prime factor for successful multimodality therapy.

Eighty-five patients (37 female, 48 male; median age 14 years) with non-metastatic Ewing's sarcoma received definitive treatment at the University of Texas M.D. Anderson Cancer Center between 1969 and 1988. Multidisciplinary therapy was administered as follows: combination chemotherapy (CC) and local radiotherapy (XRT): 65 patients; CC, XRT and surgery, 19 patients; and XRT and surgery, 1 patient. This permitted a 10-20 year follow-up for 75% of our patients. The overall survival at 5 and 10-20 years was 46.1%, and 37.2%, respectively. At 5 years, 80.5% of live patients had control of local disease. The influence of sex, age, ethnicity, primary site, size, lactic dehydrogenase (LDH) level, presence or absence of systemic symptoms, and XRT dose (<60 Gy and </=60 Gy) was analyzed and was not found to be of prognostic significance in survival. The presence of a soft tissue mass at diagnosis was found to be a significant unfavorable prognostic variable. Nine of 11 patient who underwent resection after CC and/or XRT had residual tumor in the surgical specimen. Patients who received surgery as part of the planned treatment of their primary tumor had significantly better local control and disease-free survival than those who did not undergo resection. Complications in long-term survivors are described.

Adolescent↗

A morphometric analysis of glomerular and tubular alterations following fast-neutron irradiation of the pig and monkey kidney.

PURPOSE: The morphologic responses of the pig and monkey kidney to fractionated fast-neutron irradiation were assessed. METHODS AND MATERIALS: The right kidney of approximately 14-week-old female Large White pigs was irradiated with 6.6-12.2 Gy of fast neutrons (42 MeVd-->Be) given as 12 fractions over 18 days; the left kidney served as the contralateral unirradiated kidney. Both kidneys were removed at necropsy 2 years postirradiation. In addition, the remaining hypertrophied kidney of four unilaterally nephrectomized adult rhesus monkeys was irradiated with a total dose of 11.0 Gy fast neutrons (45 MeVp-->Be) given in an identical fractionation regimen to that used in the pig studies. These kidneys were removed when the animals exhibited renal failure, between 32-94 weeks postirradiation. Glomeruli were assessed for the presence of pathologic features, including intercapillary eosinophilic material (ICE), ectatic capillaries, thrombi, hemorrhage, and sclerosis. The relative proportion of renal cortex occupied by glomeruli, interstitium, normal, or abnormal tubules was determined using a Chalkley point grid. RESULTS: The incidence of normal glomeruli, ectatic capillaries, thrombosis, and periglomerular fibrosis were significantly different in the irradiated pig kidneys compared with the unirradiated contralateral kidneys (p < or = 0.02). Linear regression analysis demonstrated a significant dose relationship in terms of normal glomeruli, ectatic capillaries, and ICE (r > or = 0.64; p < or = 0.04). Irradiation was also associated with a significant (p < 0.0001) decrease and increase in the volume of renal cortex occupied by normal and abnormal tubules, respectively. Similar morphometric changes were noted in the irradiated monkey kidneys. CONCLUSIONS: The morphologic changes seen in the pig and monkey kidney after fractionated irradiation with fast neutrons are similar to those previously noted after single-dose or fractionated-photon irradiation. These findings support the hypothesis that the development of radiation nephropathy in these various models involves common pathophysiological mechanisms.

Animals↗

Telehealth. Part II. A total system approach.

Digitization and telecommunications technology makes possible greater access to health care for remote and underserved populations. But although many telehealth programs were implemented over the last 25 years, few have survived withdrawal of external funding. This, in spite of data indicating few hardware problems and that in general patients are satisfied with their experiences of telehealth. What's the problem? Why are telehealth programs marginally successful at best?

Health Services↗

Applying radiobiological principles to combined modality treatment of head and neck cancer--the time factor.

PURPOSE: Combined modality treatment is indicated for most advanced stage head and neck cancers. It is postulated that the efficacy of combined modality regimens could be enhanced by applying principles derived from radiotherapy fractionation studies to optimize the time factor in treatment scheduling. METHODS AND MATERIALS: The premise that tumor clonogens surviving a therapeutic intervention undergo accelerated repopulation in a time-dependent fashion as their numbers are depleted is used as a model to interpret the results of various chemoradiotherapy and postsurgical radiotherapy protocols and to suggest ways in which future combined modality regimens can be more rationally designed. RESULTS: Meta-analyses of chemoradiotherapy trials show the general superiority of concomitant vs. neoadjuvant sequential protocols. There is also emerging evidence that both the duration of postoperative radiotherapy and the delay in its instigation affect treatment outcome. These results are compatible with the hypothesis that the overall duration of the "package deal" of combined modality treatment is an important determinant of outcome. However, a large decrease in duration of the "package deal" does not necessarily translate into a therapeutic gain because the total dose has to be lowered to prevent intolerable acute reactions. In these circumstances tumor control will improve only if the reduced treatment time circumvents more tumor cell regeneration than the cytoreduction that could be achieved by the extra dose tolerable in a longer time period. More modest reductions in treatment time can be accomplished without dose reduction and so avoid this risk. The design of new protocols should take account of the fact that regeneration of tumor clonogens can be predicted to be nonuniform with time. Thus, the greatest therapeutic gain should be achieved by targeting periods of maximal regenerative capacity for shortening or, alternatively, for intensification of treatment. These periods are the latter part of a course of radiotherapy or chemotherapy and the early postoperative phase after surgery. CONCLUSIONS: The rational design of combined modality protocols should include principles concerning the time factor derived from radiotherapy fractionation studies. Periods of maximal tumor cell regeneration should be targeted for shortening or for treatment intensification. Any dose sacrifice necessitated by reducing treatment duration must be less than the dose equivalent of regeneration during the same time period.

Cell Division↗

Concomitant boost radiotherapy for squamous carcinoma of the tonsillar fossa.

PURPOSE: To assess the efficacy of a concomitant boost fractionation schedule of radiotherapy for treating patients with squamous carcinoma of the tonsillar fossa. PATIENTS AND METHODS: Between December 1983 and November 1992, 83 patients with squamous carcinoma of the tonsil were treated with concomitant boost fractionation. The distribution of American Joint Committee on Cancer T stages was TX-4, T1-5, T2-29, T3-41, T4-4; N stages were NX-1, N0-26, N1-13, N2-31, N3-12. Patients were treated with standard large fields to 54 Gy in 6 weeks. The boost treatment consisted of a second daily 1.5 Gy fraction for 10-12 fractions, usually delivered during the final phase of treatment. The tumor dose was 69-72 Gy, given over 6 weeks. Twenty-one patients, who all had N2 or N3 regional disease, underwent neck dissections, either before (13 patients) or 6 weeks after radiotherapy (8 patients); the other patients were treated with radiotherapy alone. RESULTS: The 5-year actuarial disease-specific survival and overall survival rates were 71 and 60%, respectively. Patients with T2 and T3 primary tumors had 5-year actuarial local control rates of 96 and 78%, respectively. Patients with T3 disease who received the final-phase boost had a 5-year actuarial local control rate of 82%. Actuarial 5-year regional disease control rates were N0, 92%; N1, 76%; N2, 89%; and N3, 89%. The 21 patients who had neck dissections all had their disease regionally controlled. Patients presenting with nodal disease or after a node excision who were treated with radiation alone had a 5-year actuarial regional disease control rate of 79%. All but five patients had confluent Grade 4 mucositis during treatment. Severe late complications attributable to radiation included mandibular necrosis [1], in-field osteosarcoma [1], and chronic dysphagia for solid foods [5]. CONCLUSIONS: High rates of local and regional disease control were achieved with the concomitant boost fractionation schedule, with few cases of severe late morbidity. Patients with N2 and N3 neck disease were effectively treated with radiation and the selective use of neck dissections. The concomitant boost schedule is our preferred fractionation approach for treating patients with intermediate stage tonsil cancer who are not participating in our current research protocols.

Adult↗