Simple kcal/kg formula is comparable to prediction equations for estimating resting energy expenditure in older cognitively impaired long term care residents.

OBJECTIVE: Assessment of energy needs is a critical step in developing the nutrition care plan, especially for individuals unable to modulate their own energy intakes. The purpose of this study was to assess precision and accuracy of commonly used prediction equations in comparison to measured resting energy expenditure in a sample of "oldest old" adults residing in long term care (LTC). SUBJECTS AND DESIGN: Resting energy expenditure (mREE) was measured by indirect calorimetry in 45 residents aged 86.1 ± 7.3 years, and compared to frequently used prediction equations (pREE): Mifflin St.Jeor, Harris Benedict, World Health Organization and Owen. Precision and accuracy were determined by concordance correlation coefficients and number of individuals within ± 10% of mREE. Bland Altman plots with linear dependence trends were constructed to visualize agreement. To complete analyses, the common 25 kcal/kg formula was assessed and alternative formulas were determined for best fit by regressing adjusted mREE on body weight. RESULTS: mREE averaged 976.2 ± 190.3 kcal/day for females and 1260.0 ± 275.9 kcal/d for males. The strength of the relationships between pREE and mREE were only moderate (r = 0.41 - 0.72). In examining linear trends in the Bland Altman plots, significant systematic deviation from mREE was detected for all pREE. Two kcal/kg formulas were generated: 20.6 kcal/kg for females and 22.7 kcal/kg for males, which were not significantly different. CONCLUSION: None of the prediction equations adequately estimated energy needs in this sample of the "oldest old." A simple formula using 21-23 kcal/kg may be a more practical and reliable method to determine energy needs in the LTC setting.

Autologous peripheral blood hematopoietic cell transplantation in dogs with B-cell lymphoma.

BACKGROUND: Peripheral blood CD34+ hematopoietic cell transplantation (PBHCT) is commonly used to treat human patients with relapsed non-Hodgkin diffuse, large B-cell lymphoma with cure rates approaching 50%. OBJECTIVE: To determine the safety and feasibility of performing PBHCT to treat canine B-cell lymphoma (LSA) patients in a clinical academic setting. ANIMALS: Twenty-four client-owned dogs diagnosed with B-cell LSA. METHODS: After high-dose cyclophosphamide and rhG-colony-stimulating factor treatment, peripheral blood mononuclear cells were collected using cell separator machines. The harvested cells then were infused after a 10 Gy dose of total body irradiation (TBI). Post-irradiation adverse effects were managed symptomatically and dogs were discharged upon evidence of engraftment. RESULTS: More than 2 × 10(6) CD34+ cells/kg were harvested in 23/24 dogs. Preapheresis peripheral blood monocyte count was correlated with the number of CD34+ cells/kg harvested. Twenty-one of 24 (87.5%) dogs engrafted appropriately, whereas 2 dogs (8.3%) died in the hospital. One (5%) dog exhibited delayed engraftment and died 45 days after PBHCT. One dog developed presumed TBI-induced pulmonary fibrosis approximately 8 months after PBHCT. The median disease-free interval and overall survival (OS) of all dogs from the time of PBHCT was 271 and 463 days, respectively. Five of 15 (33%) dogs transplanted before they relapsed remain in clinical remission for their disease at a median OS of 524 days (range, 361-665 days). CONCLUSIONS AND CLINICAL IMPORTANCE: In most cases, PBHCT led to complete hematologic reconstitution. Therefore, PBHCT may be considered as a treatment option for dogs with B-cell lymphoma.

Continuous long-term immunomodulatory therapy in relapsing multiple sclerosis: results from the 15-year analysis of the US prospective open-label study of glatiramer acetate.

The ongoing US Glatiramer Acetate (GA) Trial is the longest evaluation of continuous immunomodulatory therapy in relapsing-remitting multiple sclerosis (RRMS). The objective of this study was to evaluate up to 15 years of GA as a sole disease-modifying therapy. Two hundred and thirty-two patients received at least one GA dose since study initiation in 1991 (mITT cohort), and 100 (43%, Ongoing cohort) continued as of February 2008. Patients were evaluated every 6 months using the Expanded Disability Status Scale (EDSS). Mean GA exposures were 8.6 +/- 5.2, 4.81 +/- 3.69, and 13.6 +/- 1.3 years and mean disease durations were 17, 13, and 22 years for mITT, Withdrawn and Ongoing cohorts, respectively. For Ongoing patients, annual relapse rates (ARRs) maintained a decline from 1.12 +/- 0.82 at baseline to 0.25 +/- 0.34 per year; 57% had stable/improved EDSS scores (change < or = 0.5 points); 65% had not transitioned to secondary progressive multiple sclerosis (SPMS); 38%, 18%, and 3% reached EDSS 4, 6, and 8. For all patients on GA therapy (the mITT cohort), ARRs declined from 1.18 +/- 0.82 to 0.43 +/- 0.58 per year; 54% had stable/improved EDSS scores; 75% had not transitioned to SPMS; 39%, 23%, and 5% reached EDSS 4, 6, and 8. In conclusion, multiple sclerosis patients with mean disease duration of 22 years administering GA for up to 15 years had reduced relapse rates, and decreased disability progression and transition to SPMS. There were no long-term safety issues.

Expression of epidermal growth factor receptor and vascular endothelial growth factor in malignant canine epithelial nasal tumours.

Epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) signalling pathways play a role in carcinogenesis. Inhibition of EGF receptor (EGFR) and of VEGF is effective in increasing the radiation responsiveness of neoplastic cells both in vitro and in human trials. In this study, immunohistochemical evaluation was employed to determine and characterize the potential protein expression levels and patterns of EGFR and VEGF in a variety of canine malignant epithelial nasal tumours. Of 24 malignant canine nasal tumours, 13 (54.2%) were positive for EGFR staining and 22 (91.7%) were positive for VEGF staining. The intensity and percentage of immunohistochemically positive neoplastic cells for EGFR varied. These findings indicate that EGFR and VEGF proteins were present in some malignant epithelial nasal tumours in the dogs, and therefore, it may be beneficial to treat canine patients with tumours that overexpress EGFR and VEGF with specific inhibitors in conjunction with radiation.

Complicaciones neurológicas de los trasplantes / Neurological complications of transplantation

El trasplante de células hematopoyéticas (TCH) y lostrasplantes de órganos han pasado a ser el tratamiento deelección de diversos procesos neoplásicos y no neoplásicos.Las complicaciones neurológicas asociadas a estos tratamientossiguen siendo frecuentes y suelen ser el resultadode la enfermedad de base, los tratamientos inmunosupresoresy la toxicidad de la radioterapia o quimioterapia. En elcaso del TCH la frecuencia y tipo de complicaciones varíancon el tipo de trasplante, autólogo o alogénico. En generallos problemas más frecuentes del TCH y los trasplantes deórganos son las encefalopatías tóxico-metabólicas y las alteracionesneurológicas centrales o periféricas debido a coagulopatías,infecciones y reactivación de procesos autoinmunes.El trastorno linfoproliferativo postrasplante (TLPT)agrupa un espectro de procesos que van desde la hiperplasialinfoide policlonal benigna a los linfomas monoclonales malignos,y suele asociarse al virus de Epstein-Barr. Algunossíndromes que eran poco conocidos o infrecuentes antes dela era de los trasplantes deben tenerse en cuenta en la evaluaciónde las complicaciones neurológicas, incluyendo elsíndrome inflamatorio de reconstitución inmunológica y algunasneuropatías paraneoplásicas relacionadas con el TLPT (AU)

Hematopoietic stem-cell transplantation (HCT) andorgan transplantation have become the standard of care for a number of malignant and non-malignant disorders.Neurological complications associated with these proceduresremain frequent. These complications result from avariety of causes including the underlying disorder, therapiesused for immunosuppression, and toxicities fromradiation or chemotherapy. For HCT the frequency of somecomplications is dependent on whether the transplantis allogenic or autologous. In general, the mainneurological problems of HCT and organ transplantationinclude metabolic and toxic encephalopathies, and centraland peripheral neurological disorders caused by coagulopathy,infections, and autoimmune mechanisms. Theterm post-transplant lymphoproliferative disorder (PTLD)includes a spectrum of disorders ranging from benignpolyclonal lymphoid hyperplasia to malignant monoclonallymphoma, usually related to the Epstein-Barr virus.Some lesser known syndromes such as the immune reconstitutioninflammatory syndrome and paraneoplasticneuropathies related with PTLD are increasingly beingdescribed and need to be considered in the evaluation ofa transplant patient with neurological problems (AU)

[Neurological complications of transplantation]. / Complicaciones neurológicas de los trasplantes.

Hematopoietic stem-cell transplantation (HCT) and organ transplantation have become the standard of care for a number of malignant and non-malignant disorders. Neurological complications associated with these procedures remain frequent. These complications result from a variety of causes including the underlying disorder, therapies used for immunosuppression, and toxicities from radiation or chemotherapy. For HCT the frequency of some complications is dependent on whether the transplant is allogenic or autologous. In general, the main neurological problems of HCT and organ transplantation include metabolic and toxic encephalopathies, and central and peripheral neurological disorders caused by coagulopathy, infections, and autoimmune mechanisms. The term post-transplant lymphoproliferative disorder (PTLD) includes a spectrum of disorders ranging from benign polyclonal lymphoid hyperplasia to malignant monoclonal lymphoma, usually related to the Epstein-Barr virus. Some lesser known syndromes such as the immune reconstitution inflammatory syndrome and paraneoplastic neuropathies related with PTLD are increasingly being described and need to be considered in the evaluation of a transplant patient with neurological problems.

Comparison of isodose distributions in canine brain in heterogeneity-corrected versus uncorrected treatment plans using 6 MV photons.

Magnetic resonance (MR) images may be useful for radiation planning due to greater contrast resolution. One disadvantage of MR images for radiation planning is the inability to incorporate electron density information into the dose calculation algorithm. To assess the magnitude of this problem, we evaluated radiation dose distribution in canine brain by comparing computed tomography (CT)-based radiotherapy plans with and without electron density correction. Computerized radiotherapy plans were generated for 13 dogs with brain tumors using 6 MV photons. A tissue-contouring program was used to outline the gross tumor volume (GTV) and the planning target volume (PTV) for each patient. Two treatment plans were generated for each dog. First, the plan was optimized without heterogeneity correction. Then the heterogeneity correction was implemented without changing any other plan parameters. Isodose distributions and dose volume histograms (DVHs) were used to compare the two plans. The D95 (dose delivered to 95% of the volume) within the PTV was calculated for each treatment plan and differences in the D95s were compared. The mean D95s without and with heterogeneity correction were 49.1 +/- 0.7 and 48.9 +/- 1.0Gy, respectively. The absolute mean percent dose difference without and with heterogeneity correction was 1.0 - 0.9% (-1.3-3.2%) and was not considered to be clinically significant. We found no clinically significant difference between CT-based radiotherapy plans without and with heterogeneity correction for brain tumors in small animals, which supports the use of MR-based treatment planning for radiotherapy of small animal brain tumors.

Changes in tumour oxygenation during fractionated hyperthermia and radiation therapy in spontaneous canine sarcomas.

Tumour oxygenation was measured in seven canine soft tissue sarcomas being treated with a fractionated course of radiation and hyperthermia. Measurements obtained during treatment were compared to pre-treatment measurements. The most important finding was an increase in oxygenation in tumours with low pre-treatment oxygenation that persisted throughout treatment. This is an advantageous hyperthermia effect as it may lead to increased radiation cell killing at each fraction. In other tumours, potentially less advantageous changes in oxygenation may be hyperthermia fractionation related and this deserves further investigation.

Episodic neurologic dysfunction with migraine and reversible imaging findings after radiation.

Reported are three adults who developed frequent episodes of a complex neurologic syndrome years after radiation therapy for a brain tumor. MRI and [(18)F]fluorodeoxyglucose PET performed during the episodes demonstrated dramatic gyral thickening with enhancement and intense hypermetabolism in symptomatic regions that resolved on follow-up studies. EEG during episodes showed only slowing. The differential diagnosis and imaging findings are reviewed.

Repair of tetralogy of Fallot with anomalous coronary arteries coursing across the obstructed right ventricular outflow tract.

Anomalous coronary artery (ACA) anatomy occurs in 2-9% of patients with tetralogy of Fallot (TOF), in which the left anterior descending coronary artery (LAD) originates from the right coronary artery (RCA) crossing the right ventricular outflow tract. The purpose of this study was to review our results of repair for TOF with ACA. Between 1978 and 2001, 43 ACA patients (mean age, 4.8 years; range, 5 months-41 years) underwent repair for TC. The ACA anatomy was classified as the single LAD from the RCA (n = 20), a significant conal branch (dual LAD) from the RCA (n = 13), paired anterior descending arteries originating from the left and right coronary arteries (n = 7), and single RCA from the LAD (n = 3). In cases in which the anomalous LAD crossed the obstructed infundibulum, thinning or coring of the endocardium was done. Patch infundibuloplasty was performed in 39 patients, with 10 needing separate RV and pulmonary artery patches, and the pulmonary valve was preserved. Nine patients had the addition of a monocusp to a transannular incision. Two patients had a main pulmonary arterioplasty alone. There was one early (2.3%) and no late deaths. Mean early and late postoperative gradients were 21.5 +/- 10.5 mmHg (4 patients had > or =30 mmHg) and 27.1 +/- 13.7 mmHg (5 patients had >30 mmHg; p = 0.12), respectively. There were four reoperations during a mean follow-up of 4.8 years (range, 6 months to 18 years). Actuarial freedom from reoperation was 90% at 5, 10, and 15 years. At the latest follow-up, all patients were in NYHA functional class I. TOF repair for an ACA can be performed without disturbing the native coronary anatomy and without the use of conduits in most cases. Outcomes are similar to those of other patients with TOF. The presence of ACA does not impose increased risk after this surgical strategy.

Glatiramer acetate (Copaxone): comparison of continuous versus delayed therapy in a six-year organized multiple sclerosis trial.

The aim of this study was to assess the long-term safety and efficacy of glatiramer acetate (GA) for patients with multiple sclerosis (MS) who received active treatment versus those on placebo for approximately 30 months (24-35 months) before receiving GA during a six-year organized, prospective open label study. Entry required two relapses in the previous two years and an Expanded Disability Status Scale (EDSS) score of 0-5. Patients (251) were equally randomized to daily subcutaneous GA, 20 mg, or to placebo. After approximately 30 months, 208 patients continued in an open label study: 101 continued on GA and 107 switched from placebo to active drug. Groups were well matched at randomization and entry to the open label study. Patients always on GA showed a steady decline in relapses: a mean of 1.5 per year at entry, a mean of 0.42 over the entire six years (95% CI = 0.34-0.51), a 72% reduction (P = 0.0001). They averaged a relapse every four + years (yearly rate 0.23 in year six) and 26/101 remain relapse free. Patients did less well if on placebo for 30 months, but relapses then declined, and by year six the rates were similar. Of patients always on GA, 69% showed neurological improvement of > or = 1 EDSS steps or remained stable compared with 57% if GA treatment was delayed. Of relapse-free patients always on GA over six years, only three of 26 (11%) were worse by > or = 1 EDSS steps, whereas nine of 21 (43%) in the placebo/active group were worse (P < 0.03). Disability, measured every six months, showed that the group of patients always on GA was relatively stable over the six years, while the group who received placebo for the first two-and-a-half years did significantly less well. Daily injections of GA were well tolerated. This longest ever organized MS treatment trial shows that delaying therapy with GA increases the risk of neurologic disability, reinforcing the rationale for using GA as a first-line treatment early in the course of relapsing-remitting MS.

Nonmyeloablative allogeneic stem cell transplantation for refractory Hodgkin's lymphoma complicated by interleukin-2 responsive progressive multifocal leukoencephalopathy.

Nonmyeloablative allogeneic stem cell transplantation (NMASCT) can be used to exploit the graft-versus-tumor (GVT) potential of allogeneic donor cells in the setting of reduced conditioning regimen toxicity. This approach is particularly attractive for patients who have received extensive prior therapy and are poor candidates for traditional allogeneic stem cell transplantation. However, toxicity in heavily pretreated patients remains uncertain. Additional immunosuppression in already immunocompromised patients may result in unexpected toxicity. We report a case of probable progressive multifocal leukoencephalopathy (PML) responsive to interleukin-2 (IL-2) following a NMASCT in a 29-year-old woman with relapsed Hodgkin's lymphoma. The patient developed severe neurological symptoms approximately 6 weeks following NMASCT associated with low CD4+ cell counts and magnetic resonance imaging (MRI) was consistent with PML. IL-2 therapy resulted in increasing CD4+ counts and progressive resolution of neurological symptoms. Disruption of IL-2 therapy led to neurological deterioration, which responded to reinstitution of IL-2 therapy. The patient's lymphoma initially progressed following NMASCT, but has responded to donor leukocyte infusions (DLI). This case reiterates the potent GVT potential of NMASCT in patients with Hodgkin's disease. However, it demonstrates the potential for severe complications related to immunosuppression, especially in heavily pretreated patients. The toxicity after NMASCT should not be understated and will need to be explored further.

Late cognitive and radiographic changes related to radiotherapy: initial prospective findings.

BACKGROUND: Assumptions about the damaging effects of radiotherapy (XRT) are based on studies in which total dose, dose fraction, treatment volume, degree of malignancy, chemotherapy, tumor recurrence, and neurologic comorbidity interact with XRT effects. This is a prospective, long-term study of XRT effects in adults, in which total dose and dose fraction were constrained and data related to tumor recurrence and neurologic comorbidity (e.g., hypertension) were excluded. METHODS: The effects of XRT on the cognitive and radiographic outcomes of 26 patients with low-grade, supratentorial, brain tumors yearly from baseline (6 weeks after surgery and immediately before XRT) and yearly to 6 years were examined. Radiographic findings were examined regionally. RESULTS: Selective cognitive declines (in visual memory) emerged only at 5 years, whereas ratings of clinical MRI (T2 images) showed mild accumulation of hyperintensities with post-treatment onset from 6 months to 3 years, with no further progression. White matter atrophy and total hyperintensities demonstrated this effect, with subcortical and deep white matter, corpus callosum, cerebellar structures, and pons accounting for these changes over time. About half of the patients demonstrated cognitive decline and treatment-related hyperintensities. CONCLUSIONS: There was no evidence of a general cognitive decline or progression of white matter changes after 3 years. Results argue for limited damage from XRT at this frequently used dose and volume in the absence of other clinical risk factors.

Sustained clinical benefits of glatiramer acetate in relapsing multiple sclerosis patients observed for 6 years. Copolymer 1 Multiple Sclerosis Study Group.

In a randomized, placebo-controlled, double-blind study, glatiramer acetate (Copaxone) reduced the relapse rate and slowed accumulation of disability for patients with relapsing - remitting multiple sclerosis. Of the original 251 patients randomized to receive glatiramer acetate or placebo, 208 chose to continue in an open-label study with all patients receiving active drug. The majority of the original double-blind cohort continues to receive glatiramer acetate by daily subcutaneous injection and are evaluated at 6-month intervals and during suspected relapse. The data reported here are from approximately 6 years of organized evaluation, including the double-blind phase of up to 35 months and the open-label phase of over 36 months. Daily subcutaneous injections of 20 mg glatiramer acetate were well tolerated. The mean annual relapse rate of the patients who received glatiramer acetate since randomization and continued into the open-label study was 0.42 (95% confidence interval (CI), CI=0.34 - 0.51). The rate per year has continued to drop and for the sixth year is 0.23. Of the group who have received glatiramer acetate without interruption for 5 or more years, 69.3% were neurologically unchanged or have improved from baseline by at least one step on the Expanded Disability Status Scale (EDSS). Patients who left the open-label phase were surveyed by questionnaire. The majority responded, providing information about their current status and reasons for dropping out. This study demonstrates the sustained efficacy of glatiramer acetate in reducing the relapse rate and in slowing the accumulation of disability in patients with relapsing forms of multiple sclerosis. Multiple Sclerosis (2000) 6 255 - 266

Radiotherapeutic effects on brain function: double dissociation of memory systems.

OBJECTIVE: The neurocognitive sequelae of therapeutic cranial irradiation are not well characterized in adults with primary brain tumors. To address this problem, we prospectively examined neuropsychological findings during two phases of radiation effects. BACKGROUND: Investigations of radiation effects have revealed variable outcomes that range from no radiation-associated morbidity to severe cognitive impairment, but have relied on case reports or retrospective studies of late-delayed changes in white matter or in cognition. No reliable radiographic or neurocognitive tools exist to describe the multiple phases of radiation effects. METHOD: Twenty adult patients (median age, 39 years) from a university hospital were treated with radiotherapy (RT) for low-grade primary brain tumors. Prospective longitudinal neuropsychological studies were compared at baseline (after surgery and before irradiation) and at 3, 6, and 12 months after RT to examine early-delayed effects, including verbal memory changes in 20 patients and visual memory changes in 11 patients. We also examined cognitive changes during the late-delayed phase for up to 3 years after RT and determined whether early-delayed memory deficit predicted late-delayed memory deficit in a small subset of patients. A comprehensive neuropsychological battery was used, including verbal and visual memory tests designed to compare learning, storage, and retrieval. RESULTS: Patients demonstrated normal verbal memory at baseline, decrement, and then rebound in verbal retrieval. Deficit at baseline and recovery up to 1 year after RT defined visual memory. Together, these observations constitute a double dissociation of memory functions. No changes over time were observed in other neurocognitive tests or in fatigue or mood measures. Time-dependent patterns of each long-term memory test were examined in relation to lesion site in individual patients. CONCLUSIONS: The double dissociation of memory functions after RT may provide markers for the damaging and facilitative early-delayed effects of RT. Late-delayed effects were not predicted based on early-delayed changes in a small sample.

The Marion Downs National Center for Infant Hearing: developing comprehensive state systems.

The Marion Downs National Center for Infant Hearing was established in 1996 through a Maternal and Child Health Grant awarded to the University of Colorado. The goals of the grant are to implement statewide systems of newborn hearing screening, audiologic assessment, and early intervention in 19 states. Newborn hearing screening alone will not assure early identification or positive outcomes for the development of communication and language. Therefore, the staff at the Marion Downs National Center developed comprehensive goals for all participating states. These goals are described in this article.

Transient MRI enhancement in a patient with seizures and previously resected glioma: use of MRS.

A 35-year-old man presented with partial seizures 10 years after resection of a left-sided glioblastoma multiforme. At the old operative site MRI demonstrated extensive cortical and white matter gadolinium enhancement, and PET showed hypermetabolism. Biopsy of the area was postponed when MRS showed a normal biochemical spectrum. MRI and PET abnormalities resolved after control of the seizures. MRS is noninvasive and can provide essential information in the management of patients with seizures and previously treated cerebral neoplasms.

Complete hepatic resection of metastases from leiomyosarcoma prolongs survival.

Although liver resection has been shown to prolong survival in selected patients with metastases from colorectal cancer, the benefit for other metastatic tumors is unproved. To determine whether hepatic resection has a role in the management of metastatic leiomyosarcoma, medical records from 11 consecutive patients who underwent resection of isolated metastases from leiomyosarcoma between 1984 and 1995 were reviewed. All liver resections were for leiomyosarcomas originating in the viscera (n = 6) or retroperitoneum (n = 5). The average disease-free interval was 16 months. Five of 11 primary tumors were classified as low grade, whereas six were high grade. Hepatic resections included lobectomy or extended lobectomy (n = 4), segmentectomy and/or wedge resection (n = 5), and complex resection (n = 2). There were no operative deaths. Median survival of all patients after liver resection was 39 months. Patients who underwent complete resection of hepatic metastases (n = 6) had a significantly longer survival than those who had incomplete resections (n = 5) (P = 0.03, log-rank test). Furthermore, five of six patients who underwent complete resection are alive after hepatectomy with a median follow-up of 53 months. Therefore, in selected patients with isolated liver metastases from visceral and retroperitoneal leiomyosarcomas, complete resection of hepatic metastases results in prolonged survival.