Detection of mutated K12-ras in histologically negative lymph nodes as an indicator of poor prognosis in stage II colorectal cancer.

Stage II colorectal carcinoma is characterized by negative lymph node pathology as determined by conventional microscopic examination. These patients generally do not receive adjuvant therapy although 20%-30% will die from metastatic disease. To determine whether K-ras mutations at codon 12 could be used as a sensitive indicator of occult lymph node metastasis in stage II colon carcinoma, a retrospective study was performed using restriction endonuclease-mediated selective polymerase chain reaction (REMS-PCR) amplification. Of 106 colonic tumors analyzed, 46 were identified as positive for a K12-ras mutation in the primary tumor. Multiple lymph node samples from 38 of these 46 patients were examined by a sensitive nested PCR protocol for the presence of a K12-ras mutation. Of these 38 patients, 14 had 1 or more positive lymph nodes by PCR (37%) and 24 were negative for the mutation (63%). Of the 14 patients with a K12-ras mutation detected in lymph nodes, 8 died of the disease within 5 years (57%) compared to only 4 of the 24 patients with ras-negative lymph nodes (17%). The difference in time to death from disease, stratified using K12-ras status of lymph nodes, was statistically significant (P = 0.036; log-rank test). These results suggest K-ras mutation status of lymph nodes in patients with stage II colon cancer might identify a subgroup of patients who are more likely to develop recurrent and/or metastatic disease and benefit from adjuvant therapy. Larger studies are indicated to determine whether detection of K-ras mutation positivity in histologically negative lymph nodes portends a poor prognosis and to determine whether more aggressive use of adjuvant therapy is warranted.

Asymptomatic hemochromatosis subjects: genotypic and phenotypic profiles.

Screening for hereditary hemochromatosis (HHC) by means of transferrin saturation (TS) levels has been advocated and will identify many patients who are asymptomatic. The purposes of this study were (1) to determine HFE genotypes among asymptomatic HHC patients and correlate this profile with the degree of iron overload and (2) to evaluate the relationship between mobilized iron (mob Fe), age, serum ferritin (SF), and quantitative hepatic iron (QHI) in this population. One hundred twenty-three asymptomatic HHC patients were evaluated; all had quantitative phlebotomy to determine mob Fe and genotyping for C282Y and H63D mutations. Liver biopsies with QHI determinations were performed on 72 of the 123 patients. Of the entire group, 60% were homozygous for C282Y, and 13% were compound heterozygotes (C282Y/H63D). Among asymptomatic patients, the prevalence of homozygous C282Y is lower compared with previous studies that include clinically affected patients. Of those patients with more than 4 g mob Fe, 77% were homozygous C282Y. Asymptomatic patients with lower iron burdens frequently had genotypes other than homozygous C282Y. There was no correlation between age and mob Fe in these patients; however, there was a correlation between mob Fe and both SF (r = 0.68) and QHI (r = 0.75). In conclusion, asymptomatic patients with moderate iron overload had a different genotypic profile than was seen in advanced iron overload. The significance of identifying patients with modest degrees of iron loading, who may not be homozygous for C282Y, must be addressed if routine TS screening is to be implemented. (Blood. 2000;96:3707-3711)

The association of basic proline-rich peptides from human parotid gland secretions with caries experience.

To address whether there are associations between the peptide composition of human parotid saliva and dental decay (caries) experience, we have characterized the peptides from parotid ductal saliva collected from nine adults who have remained free from dental caries (mean age = 59.2; Decayed Missing Filled Surfaces index [DMFS] = 0) and nine individuals who have experienced caries (mean age = 51.2; mean DMFS = 38.4). Ethanol-soluble peptides were size-fractionated on columns of Bio-Gel P-2; the salivary peptides derived from caries-susceptible subjects appeared larger than those found in the saliva of caries-free subjects. Peptides were then resolved into 19 species by cation exchange HPLC. Sequence analysis identified 18 peptides that appear to be proteolytic cleavage products of the basic proline-rich proteins IB-4, IB-5, IB-7, IB-8b, and P-B. The peptides that were more abundant in saliva obtained from the caries-free group differed from those isolated from the caries-susceptible group. The median peptide concentration of one possible precursor protein, IB-7, was found to be higher in saliva collected from caries-free individuals than in that from caries-susceptible individuals. Although differences were found in the phenotypes of proline-rich proteins expressed by these groups of caries-free and caries-susceptible subjects, no statistically significant associations were observed among proline-rich phenotypes and the level of any peptide. Collectively, our results indicate that proteolytic processing of parotid salivary proteins differs among individuals who have remained caries-free and those who have experienced dental decay.

Oral clonidine in postmenopausal patients with breast cancer experiencing tamoxifen-induced hot flashes: a University of Rochester Cancer Center Community Clinical Oncology Program study.

BACKGROUND: Hot flashes are the most frequently reported side effect of tamoxifen treatment. Although hormones are an effective treatment, their safety is questionable in women with breast cancer. It is therefore important to evaluate nonhormonal treatments for hot flashes. OBJECTIVE: To evaluate the effectiveness of oral clonidine for control of hot flashes associated with tamoxifen therapy in postmenopausal women with breast cancer. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. SETTING: University of Rochester Cancer Center Community Clinical Oncology Program. PATIENTS: 194 postmenopausal women with breast cancer who were receiving adjuvant tamoxifen therapy. INTERVENTION: Oral clonidine hydrochloride, 0.1 mg/d, or placebo for 8 weeks. MEASUREMENTS: In a daily diary, patients recorded number, duration, and severity of hot flashes and overall quality-of-life score (on a 10-point scale) during a 1-week baseline period and during the 4th, 8th, and 12th weeks of the study. RESULTS: Patients in the placebo and treatment groups were similar in age, duration of tamoxifen use, reported frequency and duration of hot flashes at baseline, and dropout rates. One hundred forty-nine patients completed 12 weeks of follow-up. The mean decrease in hot flash frequency was greater in the clonidine group than in the placebo group after 4 weeks of treatment (37% compared with 20% [95% CI for difference, 7% to 27%]) and 8 weeks of treatment (38% compared with 24% [CI for difference, 3% to 27%]). Patients receiving clonidine were more likely than patients receiving placebo to report difficulty sleeping (41% compared with 21%; P = 0.02). A significant difference was seen in the mean change in quality-of-life scores (0.3 points in the clonidine group compared with -0.2 points in the placebo group; P = 0.02) at 8 weeks, although the median difference was 0 in both groups. CONCLUSION: Oral clonidine, 0.1 mg/d, is effective against tamoxifen-induced hot flashes in postmenopausal women with breast cancer.

Allogeneic bone marrow transplantation for children with acute leukemia: cytoreduction with fractionated total body irradiation, high-dose etoposide and cyclophosphamide.

Marrow-ablative chemo-radiotherapy followed by hematopoietic stem cell rescue from an allogeneic source improves outcomes for children with high-risk acute leukemia. The first effective pre-transplant preparative regimens consisted of high-dose cyclophosphamide (CY) and total body irradiation (TBI). Subsequent attempts have been made to improve leukemia-free survival, by adding other chemotherapy agents to these agents. In previous clinical studies of total body irradiation, etoposide, cyclophosphamide (TBI-VP-16-Cy) in adult allogeneic bone marrow transplantation, there has been a high incidence of severe regimen-related toxicity. In this study, we investigated the safety and efficacy of this combination in 41 children who received TBI (12-14 Gy), VP-16 (30 mg/kg), and CY (60 mg/kg x 2) and then either matched sibling or alternative donor transplants for acute leukemia. There was only one case of fatal regimen-related toxicity. The estimated 3-year event-free survival for patients with early or intermediate stage disease was 68% (53-88%). The estimated event-free survival of patients with advanced disease was 17% (5-59%). TBI-VP16-CY is safe in pediatric transplantation, and it has good efficacy for transplant recipients with less advanced disease. Bone Marrow Transplantation (2000) 25, 489-494.

Analysis of factors that correlate with mucositis in recipients of autologous and allogeneic stem-cell transplants.

PURPOSE: To identify predictors of oral mucositis and gastrointestinal toxicity after high-dose therapy. PATIENTS AND METHODS: Mucositis and gastrointestinal toxicity were prospectively evaluated in 202 recipients of high-dose therapy and autologous or allogeneic stem-cell rescue. Of 10 outcome variables, three were selected as end points: the peak value for the University of Nebraska Oral Assessment Score (MUCPEAK), the duration of parenteral nutritional support, and the peak daily output of diarrhea. Potential covariates included patient age, sex, diagnosis, treatment protocol, transplantation type, stem-cell source, and rate of neutrophil recovery. The three selected end points were also examined for correlation with blood infections and transplant-related mortality. RESULTS: A diagnosis of leukemia, use of total body irradiation, allogeneic transplantation, and delayed neutrophil recovery were associated with increased oral mucositis and longer parenteral nutritional support. No factors were associated with diarrhea. Also, moderate to severe oral mucositis (MUCPEAK > or = 18 on a scale of 8 to 24) was correlated with blood infections and transplant-related mortality: 60% of patients with MUCPEAK > or = 18 had positive blood cultures versus 30% of patients with MUCPEAK less than 18 (P =.001); 24% of patients with MUCPEAK > or = 8 died during the transplantation procedure versus 4% of patients with MUCPEAK less than 18 (P =.001). CONCLUSION: Gastrointestinal toxicity is a major cause of transplant-related morbidity and mortality, emphasizing the need for corrective strategies. The peak oral mucositis score and the duration of parenteral nutritional support are useful indices of gastrointestinal toxicity because these end points are correlated with clinically significant events, including blood infections and treatment-related mortality.

Prevalence of hereditary hemochromatosis in 16031 primary care patients.

BACKGROUND: Despite evidence from screening studies in northern European populations, the prevalence of hemochromatosis in primary care populations in the United States remains speculative. OBJECTIVE: To establish the feasibility of screening for hemochromatosis and to estimate the prevalence of hemochromatosis in a large primary care population. DESIGN: Cross-sectional prevalence study. SETTING: 22 primary care practices in the Rochester, New York, area. PATIENTS: 16031 ambulatory patients without a previous diagnosis of hemochromatosis. INTERVENTION: Serum transferrin saturation screening tests were offered to all adult patients in participating primary care practices. MEASUREMENTS: Patients with a serum transferrin saturation of 45% or more on initial testing had a serum transferrin saturation test done under fasting conditions and had serum ferritin levels measured. Those who had a fasting serum transferrin saturation of 55% or more and a serum ferritin level of 200 microg/L or more with no other apparent cause were presumed to have hemochromatosis and were offered liver biopsy to confirm the diagnosis. RESULTS: 25 patients had biopsy-proven hemochromatosis; 22 patients met the clinical criteria for hemochromatosis but declined liver biopsy and were classified as having clinically proven hemochromatosis; and 23 patients had a serum transferrin saturation of 55% or more with no identifiable cause, indicating probable hemochromatosis. The prevalence of clinically proven and biopsy-proven hemochromatosis combined was 4.5 per 1000 (95% CI, 3.3 to 5.8 per 1000) in the total sample and 5.4 per 1000 (CI, 4.0 to 7.1 per 1000) in white persons. The prevalence was higher in men than in women (ratio, 1.8:1). CONCLUSIONS: Hemochromatosis is relatively common among white persons. Routine screening of white persons for hemochromatosis should be considered by primary care physicians.

Autotransplantation for relapsed or refractory Hodgkin's disease: long-term follow-up and analysis of prognostic factors.

Seventy consecutive patients with refractory or relapsed Hodgkin's disease who received high-dose chemotherapy followed by autologous stem cell rescue were analyzed to identify clinically relevant predictors of long-term event-free survival. High-dose therapy consisted primarily of carmustine (BCNU), etoposide, cytarabine and cyclophosphamide (BEAC). The 5-year Kaplan-Meier event-free survival (EFS) for the entire cohort was 32% (95% confidence interval; 18-45%) with a median follow-up of 3.6 years (range 7 months-7.6 years). The most significant predictor of improved survival was the presence of minimal disease (defined as all areas < or =2 cm) at the time of transplant: the 5 years EFS was 46 vs 10% for patients with bulky disease (P = 0.0002). Other independent predictors identified by step-wise regression analysis included the presence of non-refractory disease and the administration of post-transplant involved-field radiotherapy (XRT). Treatment-related mortality occurred in 13 of 70 patients: nine patients (13%) died within the first 100 days, mainly from cardiopulmonary toxicity. However, only one of 24 patients (4%) transplanted during the last 4.5 years died from early treatment-related complications. While high-dose therapy followed by autotransplantation led to long-term EFS of 50% for patients with favorable prognostic factors, a substantial proportion of patients relapsed, indicating that new therapeutic strategies are needed.

Autotransplantation for relapsed or refractory non-Hodgkin's lymphoma (NHL): long-term follow-up and analysis of prognostic factors.

One hundred and thirty-six patients autografted for relapsed or refractory non-Hodgkin's lymphoma (NHL) were evaluated to assess long-term event-free survival and to identify important prognostic factors. High-dose therapy consisted primarily of carmustine (BCNU), etoposide, cytarabine, and cyclophosphamide (BEAC) followed by unpurged autologous stem cell rescue. The 5-year Kaplan-Meier event-free survival (EFS) for the entire cohort was 34% (95% confidence interval: 24-44%) with a median follow-up of approximately 3 years (range 0-7.5 years). For patients entering with minimal disease (defined as all areas < or = 2 cm), the 5-year EFS was 40 vs 26% for those entering with bulky disease (P = 0.0004). In the multivariate analysis, minimal disease on entry and administration of involved-field XRT post-transplant were significantly associated with improved EFS; the latter association was observed mainly in the cohort of patients with bulky disease. The overall 100-day treatment-related mortality rate was 4.4% (3% for the last 71 patients). New strategies are needed to reduce the high rate of relapse (50-60%) following auto-transplantation for relapsed or refractory NHL.

Effect of emergency department immunizations on immunization rates and subsequent primary care visits.

BACKGROUND: The Standards for Pediatric Immunization Practices recommend the routine use of emergency department (ED) encounters for screening the immunization status of children and, if indicated, immunizing them. OBJECTIVE: To test the hypothesis that ED immunizations will improve immunization rates without decreasing subsequent primary care visits. DESIGN: A randomized controlled trial of 2 interventions. Children (aged 6-36 months) (n = 1835) were enrolled in the study in the ED; informed consent was obtained from their parents. They were randomized into 1 of 3 groups: (1) the control group (n = 614), in which no intervention was undertaken; (2) the letter group (n = 610), in which a letter to the primary care physician was written indicating the child's estimated likelihood of being underimmunized; and (3) the ED vaccination group (n = 611), in which, based on a decision rule, those likely to be underimmunized were offered immunizations in the ED. After randomization, parents were interviewed in the ED using a decision rule to estimate the likelihood of the child being underimmunized. One year after enrollment in the study, the medical records of the children at their primary care sites were reviewed to determine the immunization status of the children and primary care use patterns. SETTING: An urban ED and 54 primary care sites in Monroe County, New York. RESULTS: The mean age of the participants was 17.9 months. Medical record review-verified underimmunization rates at the time of the ED visit were 33%, 31%, and 28% for the control, letter, and ED vaccination groups, respectively. The demographic characteristics and baseline immunization rates were not different among study groups. According to the decision rule, 248 children (41%) in the ED vaccination group were likely to be underimmunized. Parents of these 248 children were offered immunizations for their children; 117 (47%) accepted, and their children were immunized (with 230 separate immunizations). One month after the ED visits, the underimmunization rates of the study groups were 31%, 28% (P = .40 compared with the control group), and 23% (P = .002). One year later, these rates were 28%, 25% (P = .20), and 25% (P = .20). No clinically meaningful differences were present at either of these times. One year after the ED visit, no differences in the rates of primary care use were found among groups. CONCLUSIONS: This study provides evidence that the immunization of children in this ED was ineffective at raising their immunization rates; primary care attendance was also unaltered. Major obstacles were as follows: (1) an inability to ascertain accurately the immunization status in the ED and (2) a high rate of parental refusal to accept immunizations in the ED. The standards should be modified to de-emphasize the ED as a routine immunization site for children with access to primary care. Efforts and resources should be directed toward strengthening the primary care system and tracking immunization status.

Comparison between Japan and North America in the post-hospital course after recovery from an acute coronary event.

We compared the post-hospital prognosis after an acute coronary event (acute myocardial infarction and unstable angina) in 106 patients in Japan vs. 789 patients in North America who were prospectively enrolled in the Multicenter Study of Myocardial Ischemia and were followed-up for an average of 26 months per patients. Risk factors more frequent in Japan were older age, males and smoking at enrollment, but the rest of many risk factors were similar. After adjusting for differences in clinical and medication variables, Cox analyses indicated patients in North America had a significantly greater risk of experiencing a primary end-point (cardiac death, non-fatal myocardial infarction or unstable angina) than patients in Japan (hazard ratio [North America:Japan] = 3.1, P = 0.003). There was a non-significant trend in the restricted end-points (cardiac death or non-fatal myocardial infarction) with North America having more frequent events than Japan (hazard ratio = 2.2, P = 0.12). The long-term outcome after recovery from an acute coronary event is more favorable in Japan than in North America, mostly due to a reduction in subsequent hospitalization for unstable angina. The reason for these findings cannot be explained by differences in the measured risk factors or medications.

An observer study for direct comparison of clinical efficacy of electronic to film portal images.

PURPOSE: To directly compare clinical efficacy of electronic to film portal images. METHODS AND MATERIALS: An observer study was designed to compare clinical efficacy of electronic to film portal images acquired using a liquid matrix ion-chamber electronic portal imaging device and a conventional metal screen/film system. Both images were acquired simultaneously for each treatment port and the electronic portal images were printed on gray-level thermal paper. Four radiation oncologists served as observers and evaluated a total of 44 sets of images for four different treatment sites: lung, pelvis, brain, and head/neck. Each set of images included a simulation image, a double-exposure portal film, and video paper prints of electronic portal images. Eight to nine anatomical landmarks were selected from each treatment site. Each observer was asked to rate each landmark in terms of its clinical visibility and to rate the ease of making the pertinent verification decision in the corresponding electronic and film portal images with the aid of the simulation image. RESULTS: Ratings for the visibility of landmarks and for the verification decision of treatment ports were similar for electronic and film images for most landmarks. However, vertebral bodies and several landmarks in the pelvis such as the acetabulum and public symphysis were more visible in the portal film images than in the electronic portal images. CONCLUSION: The visibility of landmarks in electronic portal images is comparable to that in film portal images. Verification of treatment ports based only on electronic portal images acquired using an electronic portal imaging device is generally achievable.

Response of Photofrin-sensitised mesothelioma xenografts to photodynamic therapy with 514 nm light.

We have studied the response of human mesothelioma xenografts in nude mice to Photofrin-sensitised photodynamic therapy with 514 nm light. Delays in tumour regrowth following four different 514 nm irradiation regimens were compared with results obtained with the more commonly used 630 nm light. One of these 514 nm regimens, which consisted of 1 h of irradiation at an incident fluence rate of 20 mW cm-2 and a second hour at a fluence rate of 28 mW cm-2, produced tumour volume doubling times that were statistically indistinguishable from results that were observed when tumours were irradiated for 2 h with 630 nm light at an incident fluence rate of 50 mW cm-2. The three other 514 nm light protocols tested were found to be less effective than the 630 nm regimen. The 514 nm treatment protocols were devised on the basis of attempts to equate the photodynamic dose and the dose rate at these two wavelengths, with photodynamic dose defined as the number of photons absorbed by the sensitiser. Photosensitiser extinction coefficients, photon energies and tissue optical properties were considered in these attempts. Our results indicate that, under certain conditions, photodynamic therapy performed with 514 nm light can provide tumour control that is similar to that achieved with 630 nm, with potential for diminished normal tissue damage.

Adjuvant chemotherapy does not affect employment in patients with early-stage breast cancer.

OBJECTIVE: To assess the impact of adjuvant chemotherapy for the management of breast cancer on subsequent patient employment. DESIGN: Retrospective cohort study. SETTING: University-affiliated community hospital cancer center. PATIENTS: Patients who were 18 to 65 years old and were diagnosed as having breast cancer stages 0, I, II, and IIIa between January 1986 and January 1991 were contacted and asked whether they had been employed at the time of the diagnosis. The 145 patients who had breast cancer and who had been working at the time of diagnosis completed a questionnaire, which included questions regarding demographic characteristics, employment history, and the reasons for any period of unemployment. The 76 patients who had received adjuvant chemotherapy were compared with the 69 who had not. MEASUREMENTS AND RESULTS: The main endpoint was return to work by one, three, six, and 12 months after surgery. Of the 76 patients who had received chemotherapy, 70 (92%) had resumed work by 12 months after treatment began. Of the 69 who had not been treated with chemotherapy, 65 (94%) had resumed work in 12 months. The proportions of patients who had returned to work by one, three, and six months were similar in the two groups. Regression analyses demonstrated no significant confounding or interaction of adjuvant treatment with age, menopausal status, marital status, years of education, or type of job in regard to return to work. CONCLUSIONS: Adjuvant chemotherapy does not delay or prevent return to work in women treated for early-stage breast cancer.

Quantification of micro-regional heterogeneities in tumor oxygenation using intravascular HbO2 saturations.

Despite promising reports as to the relationship between tumor radiosensitivity and overall tumor oxygenation, little additional information has been forthcoming regarding the importance of localized variations in tumor oxygen distribution. The objectives of the current study were (1) to devise a strategy for sampling tumor HbO2 saturation distributions and (2) to compare intratumor heterogeneities in HbO2 profiles with intertumor variability to determine whether representative tumor oxygen profiles can be obtained from a limited tumor sample. Using murine KHT fibrosarcomas, maps of tumor intravascular HbO2 saturations were obtained using cryospectrophotometric techniques and without the use of anesthetics. Micro-regions composed primarily of either high or low HbO2 vessels were observed in both peripheral and interior regions of the KHT tumors, although HbO2 levels were higher, on average, toward the periphery. To quantify intra- and intertumor heterogeneities in oxygen delivery, alternative HbO2 sampling protocols were evaluated in comparison to all-inclusive HbO2 maps for each tumor cross section. Since intratumor variations in HbO2 distributions were of the same order of magnitude as intertumor variations for tumors of a single tumor line, it is clear that tumor micro-regional physiology cannot be characterized adequately by a single regional sample.

When does palliative care begin? A needs assessment of cancer patients with recurrent disease.

This cross-sectional study compared the prevalence and intensity of needs expressed by cancer patients at the time of first recurrence (n = 75) with those of patients at the time of disease progression (n = 75). On a 72-item Likert-type scale participants rated from "none" to "very much" the severity of physical symptoms; emotional, psychological, and social problems; and difficulties with activities of daily living. The progressive disease group reported more problems than the first recurrence group in 11 of 24 (47%, p < 0.05) symptom-related questions. The progressive disease group also expressed greater needs in 19% of the function-related questions. There were no differences in reported psychological problems, responses to recurrence, or greatest concern between the two groups. These results support the need for palliative care throughout the entire course of illness.

Effects of photodynamic therapy on xenografts of human mesothelioma and rat mammary carcinoma in nude mice.

We have examined the effectiveness of photodynamic therapy against R3230AC rat mammary adenocarcinoma and human mesothelioma as xenografts in the same host. The results demonstrate that the xenografted human tumour is significantly more responsive to photodynamic treatment than the rodent mammary tumour. Studies also showed that the mesothelioma xenograft was fluence rate- and fluence-dependent while the rat tumour exposed to the same conditions demonstrated neither of these dependencies. This disparity in response was not attributable to a difference in either whole-tumour uptake or subcellular distribution of the porphyrin photosensitiser. Analysis of the effects of visible irradiation on cytochrome c oxidase activity, measured in mitochondria prepared from tumours borne on hosts injected with photosensitiser, demonstrated that photoradiation-induced enzyme inhibition was significantly greater in mesothelioma than in R3230AC mammary tumour preparations. However, in parallel studies conducted in vitro, when photosensitiser and light were delivered to previously unperturbed mitochondria, rates of enzyme inhibition were not significantly different. Both tumours were established in long-term cell culture. While the uptake of porphyrin photosensitiser was equivalent in both cell lines, the R3230AC cells displayed a significantly greater photosensitivity than the mesothelioma cells. The data presented here demonstrate that the mechanisms that govern response to photodynamic therapy are complex, but in the case of these two xenografted tumours host response to therapy is not likely to play a significant role.

Observer variation in interpretation of magnetic resonance images of the temporomandibular joint.

The purpose of this study was to measure interobserver and intraobserver variation in reporting magnetic resonance images of the temporomandibular joint. This study was based on magnetic resonance images of 149 joints. The images were interpreted independently by two of us on two occasions, 2 to 4 weeks apart. We were trained together before starting the study. The magnetic resonance images were interpreted for the position and configuration of the disk and osseous changes. The intraobserver agreement for reporting the position of the disk was 95%, configuration of the disk was 90%, and osseous changes was 97% (average of both observers). The agreement between the two observers was 90% on the position of the disk, 89% on the configuration of the disk, and 94% on reporting osseous changes (average of both readings). The results suggest that interobserver and intraobserver variation in reporting magnetic resonance images of the temporomandibular joint can be kept at a low level with high quality images, suitable training of the observers, and well-defined criteria for interpretation. The low observer variation together with the high diagnostic accuracy reported in other studies suggests that magnetic resonance imaging of the temporomandibular joint is a reliable and valid imaging technique for assessment of this joint.

The short-form McGill Pain Questionnaire in chronic cancer pain.

A short form of the McGill Pain Questionnaire (SF-MPQ) was previously developed. It was found to correlate highly with and demonstrate differences due to treatment in a manner similar to the long form of the McGill Pain Questionnaire (LF-MPQ). The LF-MPQ was previously found to be a valid measurement of pain in the cancer population. The present study demonstrated that the sensory, affective, and total scores of the SF-MPQ correlated highly with the LF-MPQ on three administrations, each 3-4 wk apart in 24 patients with chronic pain due to cancer. Both the long and short total scores correlated highly with the visual analogue scale (VAS) and present pain intensity (PPI) scale. The SF-MPQ demonstrated changes over time in a manner similar to the LF-MPQ in this patient group. These observations support the value of the SF-MPQ as a tool for studying interventions in patients with chronic pain due to cancer.

Hypothalamic-pituitary dysfunction after radiation for brain tumors.

BACKGROUND: Patients with brain tumors who are treated with radiation frequently have growth hormone deficiency, but other neuroendocrine abnormalities are presumed to be uncommon. METHODS: We studied endocrine function in 32 patients (age, 6 to 65 years) 2 to 13 years after they had received cranial radiotherapy for brain tumors. The doses of radiation to the hypothalamic-pituitary region ranged from 3960 to 7020 rad (39.6 to 70.2 Gy). Nine patients also received 1800 to 3960 rad (18.0 to 39.6 Gy) to the craniospinal axis. Serum concentrations of thyroid, gonadal, and pituitary hormones were measured at base line and after stimulation. RESULTS: Nine patients (28 percent) had symptoms of thyroid deficiency, and 20 patients (62 percent) had low serum total or free thyroxine or total triiodothyronine concentrations. Of the 23 patients treated only with cranial radiation, 15 (65 percent) had hypothalamic or pituitary hypothyroidism. Of the nine patients who also received spinal (and thus direct thyroid) radiation, three (33 percent) had evidence of primary thyroid injury. Seven of the 10 postpubertal, premenopausal women (70 percent) had oligomenorrhea, and 5 (50 percent) had low serum estradiol concentrations. Three of the 10 men (30 percent) had low serum testosterone concentrations. Overall, 14 of the 23 postpubertal patients (61 percent) had evidence of hypogonadism. Mild hyperprolactinemia was present in 50 percent of the patients. Responses to stimulation with corticotropin-releasing hormone and corticotropin were normal in all patients except one, who had panhypothalamic dysfunction. However, serum 11-deoxycortisol responses to the administration of metyrapone were low in 11 of the 31 patients (35 percent) tested. Three of the 32 patients, (9 percent) had no endocrine abnormalities, 9 (28 percent) had an abnormal result on tests of thyroid, gonadal, prolactin, or adrenal function, 8 (25 percent) had abnormalities in two axes, 8 (25 percent) in three axes, and 4 (12 percent) in all four axes. CONCLUSIONS: Cranial radiotherapy in children and adults with brain tumors frequently causes abnormal hypothalamic-pituitary function. The most frequent changes are hypothyroidism and gonadal dysfunction, although subtle abnormalities in adrenal function may also be present.