Hyponatraemia in cancer patients on an inpatient rehabilitation unit.

This study identifies the incidence of hyponatraemia in cancer patients on an inpatient rehabilitation unit and examines the association between admission hyponatraemia and rehabilitation length of stay (LOS), functional outcome, and survival. After institutional review committee's approval, we retrospectively reviewed medical records of 295 consecutive patients who were admitted to this inpatient cancer rehabilitation unit between 27 January 2009 through 31 July 2010 in a tertiary cancer centre. The incidence of hyponatraemia in cancer patients admitted to our inpatient rehabilitation unit was 41.4%. Median rehabilitation LOS for patients with mild (Na 130-134 mEq/L) and moderate-severe (Na < 130 mEq/L) hyponatraemia was 11 and 15 days, respectively, which was significantly longer than patients with eunatraemia (10 days; P = 0.03). Functional Independence Measure gain for ambulation and transfers during inpatient rehabilitation stay was not significantly different between three different patient groups. We concluded that large portion of patients who require acute inpatient rehabilitation presented with hyponatraemia, which is associated with prolonged rehabilitation LOS. Whether aggressive management of hyponatraemia will shorten rehabilitation stay needs further study.

Tibetan sound meditation for cognitive dysfunction: results of a randomized controlled pilot trial.

OBJECTIVE: Although chemotherapy-induced cognitive impairment is common among breast cancer patients, evidence for effective interventions addressing cognitive deficits is limited. This randomized controlled trial examined the feasibility and preliminary efficacy of a Tibetan Sound Meditation (TSM) program to improve cognitive function and quality of life in breast cancer patients. METHODS: Forty-seven breast cancer patients (mean age 56.3 years), who were staged I-III at diagnosis, 6-60 months post-chemotherapy, and reported cognitive impairment at study entry were recruited. Participants were randomized to either two weekly TSM sessions for 6 weeks or a wait list control group. Neuropsychological assessments were completed at baseline and 1 month post-treatment. Self-report measures of cognitive function (Functional Assessment of Cancer Therapy (FACT)-Cog), quality of life (SF-36), depressive symptoms (Center for Epidemiologic Studies Depression Scale), sleep disturbance (Pittsburgh Sleep Quality Index), fatigue (Brief Fatigue Inventory), and spirituality (FACT-Sp) were completed at baseline, the end of treatment, and 1 month later. RESULTS: Relative to the control group, women in the TSM group performed better on the verbal memory test (Rey Auditory Verbal Learning Test trial 1) (p = 0.06) and the short-term memory and processing speed task (Digit Symbol) (p = 0.09) and reported improved cognitive function (p = 0.06), cognitive abilities (p = 0.08), mental health (p = 0.04), and spirituality (p = 0.05) at the end of treatment but not 1 month later. CONCLUSIONS: This randomized controlled trial revealed that TSM program appears to be a feasible and acceptable intervention and may be associated with short-term improvements in objective and subjective cognitive function as well as mental health and spirituality in breast cancer patients.

Testosterone replacement for fatigue in hypogonadal ambulatory males with advanced cancer: a preliminary double-blind placebo-controlled trial.

BACKGROUND: Uncontrolled studies show fatigue, anorexia, depression, and mortality are associated with low testosterone in men with cancer. Testosterone replacement improves quality of life and diminishes fatigue in patients with non-cancer conditions. The primary objective was to evaluate the effect of testosterone replacement on fatigue in hypogonadal males with advanced cancer, by the Functional Assessment of Chronic Illness Therapy-Fatigue subscale (FACIT-Fatigue) at day 29. METHODS: This is a randomized, double-blinded placebo-controlled trial. Outpatients with advanced cancer, bioavailable testosterone (BT) <70 ng/dL and fatigue score >3/10 on the Edmonton Symptom Assessment Scale were eligible. Intra-muscular testosterone or sesame seed oil placebo was administered every 14 days to achieve BT levels 70-270 ng/dL. RESULTS: Sixteen placebo and 13 testosterone-treated subjects were evaluable. No statistically significant difference was found for FACIT-fatigue scores between arms (-2 ± 12 for placebo, 4 ± 8 for testosterone, p = 0.11). Sexual Desire Inventory score (p = 0.054) and performance status (p = 0.02) improved in the testosterone group. Fatigue subscale scores were significantly better (p = 0.03) in those treated with testosterone by day 72. CONCLUSIONS: Four weeks of intramuscular testosterone replacement in hypogonadal male patients with advanced cancer did not significantly improve quality of life. Larger studies of longer duration are warranted.

Heart rate variability as a measure of autonomic dysfunction in men with advanced cancer.

Autonomic dysfunction is common in patients with cancer and may have considerable negative effects on quality of life and mortality. This study retrospectively compared heart rate variability measured by the standard deviation of normal-to-normal intervals (SDNN) to Ewing test score, a composite score from a battery of five defined autonomic tests, in detection of autonomic dysfunction in 47 men with advanced cancer. The Ewing test score has been validated for diagnosis of autonomic dysfunction but is time-consuming and requires considerable patient co-operation; we hypothesised that SDNN, a much simpler test, is a useful alternative. The patients were categorised into three groups according to Ewing score: ≤ 2 (mild or no autonomic dysfunction), 2.5-3 (moderate) and ≥ 3.5 (severe). The SDNN (mean ± SD) for the three groups were 57.1 ± 26.9 ms 62.3 ± 22.4 ms and 37.7 ± 20.3 ms respectively. A significant negative correlation was found between Ewing score and SDNN (r = -0.40, P = 0.005). A SDNN of ≤ 40 ms had 63% sensitivity and 75% specificity in the diagnosis of severe autonomic dysfunction (i.e. Ewing score ≥ 3.5). The positive predictive value of SDNN ≤ 40 ms in predicting moderate/severe autonomic dysfunction was 89%.

Implementation of podiatry telephone appointments for people with rheumatic and musculoskeletal diseases.

BACKGROUND: Foot health problems are common in the general population, and particularly so in people with rheumatic and musculoskeletal disorders (RMD). Several clinical guidelines state that people with RMDs should have access to foot health services, although service capacity is often limited. The current COVID-19 pandemic has increased the need for alternative ways to provide patient care. The aim of this clinical audit was to review a newly implemented telephone follow-up appointment service conducted within the Rheumatology Podiatry Department in Leeds, UK. METHODS: Fifty-eight patients attending the Rheumatology Podiatry Department at Leeds Teaching Hospitals NHS Trust were contacted by telephone approximately 6-8 weeks following initial intervention. During the telephone consultation, all patients were asked pre-defined questions relating to their symptoms, intervention efficacy, the need for further appointments and their preference for the type of consultation. To assess the cost of the telephone consultation the number of attempts needed in order to make successful contact, the duration of the call and the number of telephone follow-up appointments completed in a working day were also recorded. RESULTS: Twenty-five patients (43%) were successfully contacted within the 6-8 weeks stipulated time frame and were included in the analysis. Of the 25 contacted, twelve (48%) patients were successfully contacted on the first attempt. Ten (40%) were successfully contacted on the second attempt. The remaining three patients (12%) required 3 or more attempts to make successful contact. Telephone consultations were estimated not to last longer than 10 min, including notes screening and documentation. Eleven patients (44%) reported an improvement in their symptoms, thirteen (52%) reported no change and one patient (4%) reported their symptoms to be worse. CONCLUSION: Telephone follow-up consultations may be a potentially cost-effective alternative to face-to-face appointments when implemented in a Rheumatology Podiatry Department, and provide an alternative way of providing care, especially when capacity for face-to-face contact is limited. The potential cost saving and efficiency benefits of this service are likely to be enhanced when telephone consultations are pre-arranged with patients.

Clinical findings and recommendations made during home visits by a palliative care specialist physician.

Little has been reported regarding the nature of home visits by palliative care specialist physicians to assist in the management of complex cases. We determined the characteristics, actionable clinical findings and recommendations made during consecutive home visits conducted by a specialist physician for patients registered with a community palliative care service. Patient demographic information and clinical records were reviewed. Ninety-one patients received a total of 104 home and residential facility visits. Median patient age was 59 (Q1-Q3, 43-72). Ten children (under the age of 14) received a total of 15 visits. Seventy-three patients (80%) had a cancer diagnosis. Median visit duration was 60 min (Q1-Q3, 45-60). The major actionable clinical findings were pain (120), gastrointestinal (115), neuropsychiatric (58), mouth and skin (33) and respiratory (29). One-third of recommendations involved changes in analgesia regimen (opioids 67, adjuvants 44). The specialist physician home visit resulted in multiple patient care recommendations. This information may help palliative care programmes improve their care for patients and families in the community.

p53 protein accumulation and gene mutation in the progression of human prostate carcinoma.

BACKGROUND: Nuclear accumulation of p53 protein has been shown to be strongly associated with missense p53 mutations. Studies of nuclear accumulation of p53 protein in prostate carcinoma cells have to date been confined to material from primary tumors. PURPOSE: We studied the accumulation of p53 protein in specimens obtained from primary and metastatic sites of prostate carcinoma. By examining the accumulation of this protein as a function of stage, histologic grade, and androgen responsiveness of the tumor, we hoped to determine the role of p53 mutation in the progression of prostate carcinoma. METHODS: The accumulation of the p53 protein in the cell nuclei was determined by immunohistochemical methods using polyclonal antibody to human p53 CM-1. The material studied consisted of formalin-fixed, paraffin-embedded tissue obtained from primary tumors and metastases of 92 patients with prostate carcinoma. Twelve samples from 11 patients were analyzed for the presence of mutations within exons 5-8 of the p53 gene (also known as TP53) by polymerase chain reaction-single-stranded conformation polymorphism (PCR-SSCP) analysis. Sequence analysis was subsequently performed on DNA obtained by polymerase chain reaction amplification of PCR-SSCP reactions produced from six different specimens. The chi-square test, Fisher's exact test, and the Freeman Halton test were used for statistical analyses of the results. RESULTS: All tumors with p53 accumulation were metastatic (stage D), poorly differentiated, and androgen independent. Nuclear accumulation of p53 protein was strongly associated with stage (D2 versus D1 versus A-C, P < .0001), grade (Gleason score 8-10 versus 5-7, P < .003), and androgen sensitivity (androgen independent versus dependent, P < .0001). Logistic regression analysis demonstrated that androgen sensitivity predicted p53 outcome better than did stage (P < .0001) or grade alone (P < .006). There was a perfect concordance between the results obtained by PCR-SSCP analysis and the p53 protein accumulation determined by immunohistochemistry in the 12 samples studied. Mutation of the p53 gene was confirmed by sequencing DNA obtained from six specimens positive in the PCR-SSCP assay. CONCLUSIONS: p53 gene mutation is a late event in the progression of prostate cancer and is associated with advanced (metastatic) stage, loss of differentiation, and the transition from androgen-dependent to androgen-independent growth. IMPLICATION: Testing of prostate cancer biopsy specimens from metastatic sites for p53 protein accumulation and gene mutation may provide useful prognostic information and could influence the recommended course of treatment.

The role of the cyclic AMP-dependent protein kinase in the glucagon-stimulated phosphorylation of ATP-citrate lyase.

We have examined the mechanism whereby glucagon stimulates the phosphorylation of ATP-citrate lyase in intact rat hepatocytes. Purified ATP-citrate lyase is phosphorylated in vitro by the catalytic subunit of the cyclic AMP-dependent protein kinase, in a reaction wherein 2-3 mol phosphate/mol lyase are incorporated, at an initial rate that approaches that observed for mixed histone. This reaction is completely abolished by the protein kinase inhibitor protein. Limited tryptic digestion of ATP-citrate lyase phosphorylated in vitro by the cyclic AMP-dependent protein kinase yields a pattern of 32P-labeled peptides, indistinguishable from those observed in parallel digests of lyase isolated from 32P-labeled, glucagon-stimulated hepatocytes. Phosphorylase b kinase catalyzes the incorporation of 1 mol phosphate/mol lyase, albeit at less than 1/160 the rate observed for phosphorylase b. The phosphorylation of purified ATP-citrate lyase is also catalyzed by homogenates of hepatocytes. This reaction is stimulated by cyclic AMP. At 30 degrees C, in the presence of maximally stimulating concentrations of cyclic AMP, the addition of excess protein kinase inhibitor protein inhibits the phosphorylation of ATP-citrate lyase by 67%. Thus, hepatocytes contain both cyclic AMP-dependent and cyclic AMP-independent ATP-citrate lyase kinase activities. Pretreatment of hepatocytes with glucagon (10(-8) M for 2 min) prior to homogenization results in activation of an endogenous hepatocyte ATP-citrate lyase kinase, as well as histone kinase and phosphorylase b kinase; the glucagon-stimulated increment in lyase kinase (and histone kinase) is observed only when homogenates are assayed in the absence of added cyclic AMP, and is completely abolished by an excess of the protein kinase inhibitor protein. We conclude that the glucagon-stimulated phosphorylation of ATP-citrate lyase in intact hepatocytes is catalyzed directly by the cyclic AMP-dependent protein kinase.

Complementary/alternative medicine use in a comprehensive cancer center and the implications for oncology.

PURPOSE: Oncologists are aware that their patients use complementary/alternative medicine (CAM). As cancer incidence rates and survival time increase, use of CAM will likely increase. This study assessed the prevalence and predictors of CAM use in a comprehensive cancer center. SUBJECTS AND METHODS: Subjects were English-speaking cancer patients at least 18 years of age, attending one of eight outpatient clinics at The University of Texas M.D. Anderson Cancer Center, Houston, TX, between December 1997 and June 1998. After giving written informed consent, participants completed a self-administered questionnaire. Differences between CAM users and nonusers were assessed by chi(2) and univariate logistic regression analysis. A multivariate logistic regression model identified the simultaneous impact of demographic, clinical, and treatment variables on CAM use; P values were two-sided. RESULTS: Of the 453 participants (response rate, 51.4%), 99.3% had heard of CAM. Of those, 83.3% had used at least one CAM approach. Use was greatest for spiritual practices (80.5%), vitamins and herbs (62.6%), and movement and physical therapies (59.2%) and predicted (P <.001) by sex (female), younger age, indigent pay status, and surgery. After excluding spiritual practices and psychotherapy, 95.8% of participants were aware of CAM and 68.7% of those had used CAM. Use was predicted (P <.0001) by sex (female), education, and chemotherapy. CONCLUSION: In most categories, CAM use was common among outpatients. Given the number of patients combining vitamins and herbs with conventional treatments, the oncology community must improve patient-provider communication, offer reliable information to patients, and initiate research to determine possible drug-herb-vitamin interactions.

CD30 ligand in lymphoma patients with CD30+ tumors.

PURPOSE: CD30 ligand (CD30L), which is expressed on resting B and activated T lymphocytes, can induce cell death in several CD30+ cell lines. Patients with CD30+ tumors (Hodgkin's disease and Ki-1+ non-Hodgkin's lymphoma) frequently have elevated soluble CD30 (sCD30) levels in their serum, which correlates with a poor prognosis. The role of sCD30 in protecting tumor cells from CD30L-mediated cell death and the pattern of CD30L expression on human peripheral-blood lymphocytes (PBLs) of normal donors and patients with CD30+ tumors are investigated. MATERIALS AND METHODS: CD30L surface protein expression was determined by two-color flow cytometry on PBLs of patients with CD30+ tumors and normal individuals. CD30L levels were determined on subsets of PBLs before and after stimulation with phytohemagglutinin (PHA), anti-CD3 antibody, or CD40L. sCD30 was measured by enzyme-linked immunosorbent assay (ELISA). The apoptotic activity of membrane-bound CD30L was tested in a CD30+ cell line by the annexin V-binding method. RESULTS: Unstimulated T lymphocytes of normal donors and patients with lymphoma rarely expressed CD30L surface protein, but were able to express it after stimulation with PHA or anti-CD3 antibody. Resting B cells of patients with CD30+ tumors had lower levels of detectable surface CD30L compared with normal donors (mean, 55% and 80.6%, respectively; P = .0008). Patients with high levels of serum sCD30 had lower detectable levels of CD30L on their PBLs (R2 = .72, P = .0008) and exogenous sCD30 blocked membrane-bound CD30L-mediated apoptosis in a CD30+ cell line. CONCLUSION: In patients with CD30+ tumors, sCD30 can decrease the availability of CD30L on PBLs. Blocking the apoptosis-inducing activity of CD30L by its soluble receptor may explain how CD30+ tumors escape immunosurveillance and may be related to the reported poor prognosis of patients who have elevated sCD30 levels.

Hyper-CVAD and high-dose methotrexate/cytarabine followed by stem-cell transplantation: an active regimen for aggressive mantle-cell lymphoma.

PURPOSE: Diffuse and nodular forms of mantle-cell lymphoma (MCL) are consistently associated with poor prognosis. In an effort to improve the outcome, we adopted a treatment plan that consisted of four courses of fractionated cyclophosphamide (CY) 1,800 mg/m2 administered with doxorubicin (DOX), vincristine (VCR), and dexamethasone (Hyper-CVAD) that alternated with high-dose methotrexate (MTX) and cytarabine (Ara-C). After four courses, patients were consolidated with high-dose CY, total-body irradiation, and autologous or allogeneic blood or marrow stem-cell transplantation. PATIENTS AND METHODS: Forty-five patients were enrolled; 25 patients were previously untreated, 43 patients had Ann Arbor stage IV disease, and 42 patients had marrow involvement. Forty-one patients had diffuse histology, two patients had nodular, and two patients had blastic variants. RESULTS: Hyper-CVAD/MTX-Ara-C induced a response rate of 93.5% (complete response [CR], 38%; partial response [PR], 55.5%) after four cycles of pretransplantation induction chemotherapy. All patients who went on to undergo transplantation achieved CRs. For the 25 previously untreated patients, the overall survival (OS) and event-free survival (EFS) rates at 3 years were 92% (95% confidence interval [CI], 80 to 100) and 72% (95% CI, 45 to 98) compared with 25% (95% CI, 12 to 62; P = .005) and 17% (95% CI, 10 to 43; P = .007), respectively, for the previously treated patients. When compared with a historic control group who received a CY, DOX, VCR, and prednisone (CHOP)-like regimen, untreated patients in the study had a 3-year EFS rate of 72% versus 28% (P = .0001) and a better OS rate (92% v 56%; P = .05). Treatment-related death occurred in five patients: all were previously treated and two received allogeneic transplants. CONCLUSION: The Hyper-CVAD/MTX-Ara-C program followed by stem-cell transplantation is a promising new therapy for previously untreated patients with MCL.

A rapid chemical means for removing labile glycohemoglobin.

We have devised a rapid and convenient method of eliminating the contribution of labile glycosylated hemoglobin in the hemoglobin A1 assay. The procedure requires a 30-min incubation of erythrocytes in 30 mM semicarbazide and 12 mM aniline (pH 5, 38 degrees C). This chemical means of eliminating the labile fraction is as effective as a 14-h incubation in isotonic saline as measured with high-pressure liquid chromatography or electrophoresis methods. The removal of the labile glycosylated hemoglobin fraction preserves the assay as a reliable index of chronic metabolic control.

Trisomy 7 by dual-color fluorescence in situ hybridization: a potential biological marker for prostate cancer progression.

Smear preparations from fine-needle aspirates of 30 prostatic carcinomas obtained from radical prostatectomy specimens were examined by a dual-color fluorescence in situ hybridization (FISH) method for the presence of chromosome 7 trisomy (chromosome 9 was used as a control). The frequency of cells with trisomy 7 was determined in tumor cells and normal prostatic epithelial cells in each specimen. Comparison between the tumor and normal cells from the same patients showed that within all stages, the frequency of trisomy 7/disomy 9 cells in the tumor cells was significantly higher than that observed in the normal cells (P < 0.0001). Furthermore, the mean frequency of cells with trisomy 7/disomy 9 in advanced stages was significantly elevated over the mean frequency observed in organ-confined tumors (P = 0.02). These results are consistent with our previous data on paraffin-embedded prostate tissue sections using single-color FISH procedures. However, the method used in the present study enhances the accuracy of distinguishing trisomic 7 cells from potentially triploid (trisomy 7/trisomy 9) cells. Furthermore, the use of fine-needle aspirates rather than paraffin sections provides an easy method to examine whole nuclei. Our study also suggests that FISH provides a better measure of genetic instability (e.g., aneuploidy) in prostate tumors than flow cytometry.

p53 and RB expression predict progression in T1 bladder cancer.

The optimal clinical management of minimally invasive (stage T1) bladder cancer is controversial. T1 bladder cancers share characteristics of both noninvasive (Ta) papillary cancer and high stage, muscle-invasive bladder cancers. Patients with T1 bladder cancer have a higher risk of cancer progression and death than do patients with Ta bladder cancer. However, this risk is much lower than that of patients with high-stage bladder cancers. Methods of identifying T1 bladder cancer patients at greatest risk for progression may significantly improve clinical management. We retrospectively evaluated two tumor suppressor genes, p53 and RB, as potential prognostic markers for progression in a cohort of 45 patients with pT1 bladder cancer. Median follow-up for these individuals was greater than 3.5 years. Of this group, 58% had altered p53 expression based on positive p53 immunostaining. Three patterns for RB nuclear protein staining were observed: absent, heterogeneous (normal), and strongly homogeneous. Progression-free survival was similar for patients with loss of RB protein expression and those with apparent overexpression of RB protein. Therefore, both staining patterns were considered abnormal. Patients with normal expression of both proteins (i.e., p53 negative and RB heterogeneously positive) had an excellent outcome, with no patient showing disease progression, whereas patients with abnormal expression of either or both proteins had a significant increase in progression (P = 0.04 and P = 0.005, respectively). These data support the stratification of T1 bladder cancer patients based on p53 and RB nuclear protein status and suggest that patients with normal protein expression for both genes can be managed conservatively, whereas patients with alterations in one and particularly both genes require more aggressive treatment.

Glycerol prevents insulin precipitation and interruption of flow in an implantable insulin infusion pump.

Insulin precipitation is a major obstacle to the use of implantable insulin infusion pumps. In one such pump (Infusaid, Infusaid Corporation, Norwood, Massachusetts), unprotected insulin precipitated and occluded nine pumps implanted in normal dogs within 43 days. In contrast, two similar pumps containing insulin mixed with 80% glycerol functioned normally for more than 250 days. In human studies, a similar mixture allowed insulin to be delivered to nine diabetic subjects for more than 6 mo in each case; total fluid flow rates from the pump were essentially unchanged after 460 patients-weeks of insulin infusion. A possible drawback of the mixture is a time- and temperature-dependent propensity to cause the formation of soluble, higher-molecular-weight insulin polymers, which apparently have lower biologic activity. Formation of such polymers and maintenance of biologic activity were largely prevented by the addition of phosphate buffer at neutral pH.

Spinal bone mineral density in 335 normal and obese children and adolescents: evidence for ethnic and sex differences.

Spinal bone mineral density (BMD) and anthropometric measures were studied in 312 nonobese and 23 obese black, white and Hispanic children and adolescents age 5.00-18.99 years. In adolescents BMD correlated with age, weight, height, fat-free density, body mass index, and midarm circumference. Utilizing the entire group of 312 nonobese subjects, mean Z scores were calculated for comparison versus reference subgroups for bone mineral density index (BMDI, BMD/weight). BMDI was greater for black than for white and Hispanic children and adolescents across all ages studied. Female adolescents accumulated spinal mineral more rapidly than male adolescents. Black males had greater mineral than white and Hispanic males. Differences in BMDI between subgroups could not be explained by differences in body weight or spinal vertebral size. BMDI proved a more sensitive measure for comparing subgroups than did BMD. The study provides normative data and a quantitative methodology for analyzing differences in spinal mineral between groups of children and adolescents.

Significance of tumor size and radiation dose to local control in stage I-III diffuse large cell lymphoma treated with CHOP-Bleo and radiation.

PURPOSE: The purpose of this study was to evaluate the possible effect of adjunctive involved field (IF) radiotherapy on long-term local control for patients with Ann Arbor Stage I-III diffuse large cell lymphoma (DLCL) who achieved a complete remission on a combined modality program which included cyclophosphamide, doxorubicin, vincristine, prednisone, and Bleomycin (CHOP-Bleo). METHODS AND MATERIALS: One hundred and ninety patients with Ann Arbor Stage I-III DLCL were treated with CHOP-Bleo and radiotherapy. Analyses were undertaken to determine (a) response to treatment according to stage, extent of maximum local disease, and irradiation dose either < 40 Gy or > or = 40 Gy and (b) relapse patterns. RESULTS: A complete remission (CR) was achieved in 162 patients. Among patients who achieved a CR, local control was better for those who received tumor doses of > or = 40 Gy (97%) than for those who received < 40 Gy (83%) (p = 0.002.) Among those with extensive local disease, the corresponding control rates were 88% and 71%, respectively. A study of distant relapse patterns following a CR showed that the first relapse usually involved an extranodal site. CONCLUSION: Radiotherapy was an effective adjunctive treatment to CHOP-Bleo for patients with stage I-III DLCL who achieved a CR. Patterns of relapse suggested that total nodal irradiation (TNI) possibly could have benefited a small subset of patients.

Hodgkin's disease: correlation of clinical characteristics with probabilities for negative lymphangiogram vs. negative laparotomy findings in patients with Stage I supradiaphragmatic presentations vs. those in patients with Stage II.

PURPOSE: At a time both when late complications and second malignancies have become a growing concern and when staging laparotomy has been largely abandoned and comparative studies for staging Hodgkin's disease by state of the art computed tomography (CT) vs. lymphangiography have revealed minimal differences in results for these procedures, our purpose for undertaking this study was twofold. Our initial reason was to determine and compare probabilities for negative abdominal findings for patients with Stage I presentations with those for patients with Stage II as determined by lymphangiography and subsequently by laparotomy for those patients who had negative lymphangiograms. Our second reason, being an extension of the first, was to create a resource that can be used in conjunction with other information for arriving at appropriate treatment decisions including giving either more or particularly less than standard institutional therapy and especially with respect to the abdomen. METHODS AND MATERIALS: Data on 714 patients with prelymphangiogram Stage I-II upper torso presentations of Hodgkin's disease were entered prospectively in our database between 1968 and 1987. Twenty-eight with lymphocyte predominant disease, who had both negative lymphangiogram and negative laparotomy findings and 17 with questionable diagnoses of lymphocyte-depleted or unclassified disease were excluded from subsequent analyses of 669 patients with nodular sclerosis (NS) and mixed cellularity (MC) diagnoses. RESULTS: Stage I: in final logistic models, negative lymphangiogram findings were associated strongly with a combination of no constitutional symptoms and nodular sclerosis histology, whereas negative laparotomy findings correlated strongly with a combination of no constitutional symptoms and female sex. Predicted probabilities depended on the ratios of favorable to unfavorable characteristics. Stage II: in final logistic models, negative lymphangiogram findings were associated strongly with a combination of no constitutional symptoms, nodular sclerosis histology, age <40 years, and <4 involved sites, whereas negative laparotomy findings correlated strongly with a combination of <4 involved sites and mediastinal disease. Predicted probabilities again depended on the ratios of favorable to unfavorable characteristics. CONCLUSION: This study demonstrated that probabilities for negative abdominal findings for patients with supradiaphragmatic presentations of NS and MC Hodgkin's disease depended on: 1) whether the disease presented as Stage I or as Stage II; 2) whether staging was limited to a lymphangiogram or whether it included a laparotomy; and 3) or whether the clinical features associated with the presenting stage and methods of staging were favorable or unfavorable.

Physiology of chemotherapy-induced emesis and antiemetic therapy. Predictive models for evaluation of new compounds.

The physiology of emesis has been studied for several hundred years, focusing on the different centres involved and the mechanics of expulsion. The vomiting centre receives inputs from various emetic detectors such as the gut, the vestibular labyrinths and the chemoreceptor trigger zone. Emesis is a common disabling effect in motion sickness, postoperative conditions and in radio- and chemotherapy. Our current understanding of the mechanisms has been provided mainly by the recent introduction of serotonin 5-HT3 receptor antagonists into therapeutic use. Nevertheless, despite the considerable advances made in the understanding of the different pathways involved in emesis, there are number of areas that still require experimental investigation. Different animal and human models are available to study the physiology of emesis and to evaluate the antiemetic activity of new compounds, but they need to be predictors of clinical situations.

Cytogenetic and molecular genetic analysis of a pediatric pleomorphic sarcoma reveals similarities to adult malignant fibrous histiocytoma.

Cytogenetic and molecular genetic studies were performed on a pleomorphic sarcoma removed from the left atrium of a 15-year-old girl. Histologic analysis was consistent with a storiform-pleomorphic malignant fibrous histiocytoma (MFH). Although MFH is the most common soft-tissue sarcoma of late adulthood. It is extremely rare in childhood and its existence in the pediatric population remains controversial. Cytogenetic analysis revealed several alterations previously associated with adult MFH, including abnormalities of chromosomal bands 11p11 and 19p13. Moreover, the tumor demonstrated homogeneously staining regions (HSR) and double minute chromosomes (dmin) suggestive of gene amplification. We therefore screened the case for amplification of genes localized to chromosomal bands 12q13-14, including the putative protooncogenes MDM2, CDK4, SAS, CHOP, and CLI, which are frequently amplified and overexpressed in adult MFH. Southern and Northern blot analysis confirmed the coamplification of MDM2, CDK4, SAS, and CHOP. To our knowledge, such coamplification studies of the 12q13-14 amplicon have not been previously detected in pediatric MFH. Our results provide cytogenetic and molecular genetic evidence that pediatric and adult MFH are histogenetically related entities.