Functional outcomes and quality of life in patients with brain tumors: a preliminary report.

OBJECTIVES: To determine the relationship between functional outcome and quality of life (QOL) in patients with brain tumors receiving inpatient rehabilitation, and to assess the sensitivity of 4 assessment tools in measuring changes in that population. DESIGN: Prospective study using longitudinal data collected from consecutively admitted patients. SETTING: Acute inpatient rehabilitation unit. PARTICIPANTS: Ten patients with primary brain tumors admitted to an acute inpatient rehabilitation unit. INTERVENTIONS: Patients participated in an inpatient interdisciplinary rehabilitation program that used the following disciplines: occupational therapy, rehabilitation therapy, recreational therapy, speech therapy, physical therapy, rehabilitation nursing and case management. MAIN OUTCOME MEASURES: The FIM instrument, Disability Rating Scale (DRS), Karnofsky Performance Status Scale (KPS), Functional Assessment of Cancer Therapy-Brain (FACT-BR). RESULTS: Improvement in total functional outcome was indicated by all 3 functional measures (FIM: F = 46.84, p < .05; DRS: F = 19.25, p < .05; KPS: F = 10.11, p < .05). Significant improvements were found between admission and discharge scores for the FIM and DRS. The KPS revealed significant improvement between admission and 3-month follow-up scores. All admission and discharge functional scales (FIM, DRS, KPS) correlated significantly with each other. No significant change was noted in the FACT-BR between admission and discharge scores, but FACT-BR scores did improve at 1- and 3-months postdischarge relative to admission. The FIM, KPS, and DRS did not show significant correlation with the FACT-BR. Ninety percent of patients were initially discharged to a home environment. CONCLUSION: Although patients make functional gains during and after inpatient rehabilitation, gains in QOL are not significant until 1 month postdischarge. QOL does not appear to correlate well with functional outcomes. Further, the KPS is less sensitive than the FIM and DRS in detecting change in functional status.

Functional outcomes and quality of life in patients with brain tumours: a review of the literature.

OBJECTIVE: To review the literature with respect to functional outcomes and quality of life as it pertains to individuals with brain tumours. MAIN OUTCOMES: Most functional outcome papers have focused on acute inpatient rehabilitation. In general, patients with brain tumours have comparable rates of functional gains as other models of neurologic disability. Tumour type and concomitant treatment do not impact functional outcome. Functional independence may predict survivability in certain populations. Numerous instruments are used to measure the multiple facets of quality of life. Depression, anger and fatigue can impact both physical and psychological aspects of quality of life. The physical and functional aspects can vary depending on the tumour type. Treatment regimens can negatively impact quality of life. CONCLUSION: Brain tumour patients experience changes in function and quality of life during their disease course. Rehabilitation services may offer a unique opportunity to influence both functional outcome and more closely assess quality of life in these individuals.

Acquired limb deficiencies. 2. Perioperative management.

UNLABELLED: This self-directed learning module highlights recent advances in the evaluation and management of complications arising from diabetes and peripheral vascular disease leading to amputation. It is part of the chapter on acquired limb deficiencies in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This article includes discussion of comorbid conditions that may have an impact on the prosthetic rehabilitation of a transtibial amputee. It also offers essential information regarding perioperative management of an upper extremity amputee. OVERALL ARTICLE OBJECTIVE: To review recent advances in the evaluation and management of complications arising from diabetes and peripheral vascular disease leading to amputation.

Acquired limb deficiencies. 3. Prosthetic components, prescriptions, and indications.

UNLABELLED: This self-directed learning module highlights indications for prosthetic components and prescription formulation for adults with acquired limb deficiency. It is part of the chapter on acquired limb deficiencies in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. Advantages and disadvantages of specific components of upper and lower limb prostheses are discussed, and a sample prescription sheet for upper limb devices is included. Recent innovations in terminal devices for upper limb prostheses are reviewed. Special considerations for the adult with acquired multilimb deficiency are also examined. OVERALL ARTICLE OBJECTIVE: To describe indications for prosthetic components and prescription formulation for adults with acquired limb deficiency.

Age-related differences in length of stays, hospitalization costs, and outcomes for an injury-matched sample of adults with paraplegia.

OBJECTIVE: To investigate the effects of age at injury on neurological and functional outcomes and hospitalization length of stays and charges following spinal cord injuries resulting in paraplegia. METHODS: Subjects were 180 adults with paraplegia who were assessed in acute care and inpatient rehabilitation as part of the National Institute on Disability and Rehabilitation Research Model Spinal Cord Injury Systems. Age differences were examined by separating the sample into 3 age groups (18-39, 40-59, and 60+ years). A matched block design was used to control for injury characteristics. Cramer's statistic was used to identify age-related differences in qualitative variables; 3 x 5 one-way analysis of variance identified the main effects of age on quantitative variables. Tukey post hoc tests were performed to identify differences between age and age x injury characteristic variable levels. OUTCOME AND TREATMENT MEASURES: American Spinal Injury Association motor index scores, Functional Independence Measure (FIM) motor scores, discharge to private residence ratios, and hospitalization length of stays and charges were outcome and treatment measures. RESULTS: Age-related differences were found for etiology and health care plan, as well as for preinjury marital status, education level, and employment status. The main effects of age at injury were found for the following treatment and outcome measures: rehabilitation length of stays, FIM motor scores at rehabilitation discharge, FIM motor improvement (change), and FIM motor daily improvement (efficiency). Tukey post hoc tests revealed that older patients had longer rehabilitation stays, lower rehabilitation discharge FIM motor scores, and showed less improvement compared with younger and middle-aged injury-matched patients. No age-related differences were found in rates of discharge disposition. CONCLUSIONS: Using a matched block design procedure, older patients are discharged with lower levels of functional independence and show lower levels of improvement despite longer rehabilitation stays when compared with younger patients. Older patients' neurological recovery appears equivocal to younger patients' recovery. In contrast to findings with a matched tetraplegia sample, older and younger patients with paraplegia are discharged to private residences at similar rates.

POL32, a subunit of the Saccharomyces cerevisiae DNA polymerase delta, defines a link between DNA replication and the mutagenic bypass repair pathway.

Pol32 is a subunit of Saccharomyces cerevisiae DNA polymerase delta required in DNA replication and repair. To gain insight into the function of Pol32 and to determine in which repair pathway POL32 may be involved, we extended the analysis of the pol32delta mutant with respect to UV and methylation sensitivity, UV-induced mutagenesis; and we performed an epistasis analysis of UV sensitivity by combining the pol32delta with mutations in several genes for postreplication repair (RA D6 group), nucleotide excision repair (RAD3 group) and recombinational repair (RAD52 group). These studies showed that pol32delta is deficient in UV-induced mutagenesis and place POL32 in the error-prone RAD6/ REV3 pathway. We also found that the increase in the CAN1 spontaneous forward mutation of different rad mutators relies entirely or partially on a functional POL32 gene. Moreover, in a two-hybrid screen, we observed that Pol32 interacts with Srs2, a DNA helicase required for DNA replication and mutagenesis. Simultaneous deletion of POL32 and SRS2 dramatically decreases cellular viability at 15 degrees C and greatly increases cellular sensitivity to hydroxyurea at the permissive temperature. Based on these findings, we propose that POL32 defines a link between the DNA polymerase and helicase activities, and plays a role in the mutagenic bypass repair pathway.

Functional outcomes in patients with brain tumor after inpatient rehabilitation: comparison with traumatic brain injury.

OBJECTIVE: To compare the functional outcome, length of stay, and discharge disposition of individuals with brain tumor versus those with acute traumatic brain injury. DESIGN: In this study, 78 brain tumor patients were one-to-one matched by location of lesion and age with 78 acute traumatic brain injury patients. Outcome was measured by using the Functional Independence Measure (FIM 228) on admission and discharge. The FIM change and FIM efficiency were also calculated. FIM data were analyzed in three subsets, i.e., activities of daily living, mobility, and cognition. Discharge disposition and rehabilitation length of stay were also compared. RESULTS: Demographic variables of race, marital status, and payer source were comparable for the two groups. No significant difference was found between the brain tumor and the traumatic brain injury populations with respect to total admission FIM, total discharge FIM, and FIM efficiency. The brain injury population had a significantly greater change in FIM. The tumor group had a significantly shorter rehabilitation length of stay and a greater discharge to community rate. CONCLUSIONS: Thus, individuals with brain tumor can achieve comparable functional outcome and have a shorter rehabilitation length of stay and greater discharge to community rate than individuals with brain injury.

Neoplastic vs. traumatic spinal cord injury: an inpatient rehabilitation comparison.

OBJECTIVE: To compare demographics, injury characteristics, and functional outcomes of patients with neoplastic spinal cord compression with those with traumatic spinal cord injuries. DESIGN: A prospective 5-yr comparison was undertaken comparing 34 patients with neoplastic spinal cord compression with 159 patients with traumatic spinal cord injury. RESULTS: Patients with neoplastic spinal cord compression were significantly older, more often female, and unemployed than patients with traumatic spinal cord injury. Neoplastic spinal cord compression presented more often with paraplegia involving the thoracic spine, and injuries were more often incomplete compared with traumatic spinal cord injury. Patients with neoplastic spinal cord compression had a significantly shorter rehabilitation length of stay compared with those with traumatic spinal cord injury. The neoplastic group had significantly lower FIM change scores. Both groups had similar FIM efficiencies and discharge to home rates. CONCLUSIONS: Patients with neoplastic spinal cord compression have different demographic and injury characteristics but can achieve comparable rates of functional gains as their traumatic spinal cord injury counterparts. Although patients with traumatic injuries achieve greater functional improvement, patients with neoplasms have a shorter rehabilitation length of stay and comparable FIM efficiencies and home discharge rates.

A comparative study of outcomes and expenses following tetraplegia and paraplegia.

OBJECTIVE: A study was designed to directly compare individuals with tetraplegia and paraplegia to further explore neurological and functional outcomes and their impact on the expense of rehabilitation when controlling for level of completeness, age at the time of injury, and length of stay. METHODS: A sample was drawn from the National Spinal Cord Injury Database consisting of 2069 individuals, 1005 with paraplegia and 1064 with tetraplegia. RESULTS: Significant demographic differences were found between the 2 groups with regard to age, ethnicity, marital status, and employment status. Significant differences were found between the groups with regard to all individual outcome variables (p < .001) and expenses (p < .05). On average, patients with paraplegic injuries evidenced greater change and efficiency on a functional independence measure than patients with tetraplegia. In contrast, patients with tetraplegia showed greater changes and efficiency with regard to ASIA Motor Index scores. Higher rehabilitation expenses were found for patients with tetraplegia.

Neoplastic versus traumatic spinal cord injury: an outcome comparison after inpatient rehabilitation.

OBJECTIVE: To compare outcomes of patients with neoplastic spinal cord compression (SCC) to outcomes of patients with traumatic spinal cord injury (SCI) after inpatient rehabilitation. DESIGN: A comparison between patients with a diagnosis of neoplastic SCC admitted to an SCI rehabilitation unit and patients with a diagnosis of traumatic SCI admitted to the regional Model Spinal Cord Injury Centers over a 5-year period, controlling for age, neurologic level of injury, and American Spinal Injury Association impairment classification. SETTING: Tertiary university medical centers. PATIENTS: Twenty-nine patients with neoplastic SCC and 29 patients with SCI of traumatic etiology who met standard rehabilitation admission criteria. MAIN OUTCOME MEASURES: Acute and rehabilitation hospital length of stay (LOS), Functional Independence Measure (FIM) scores, FIM change, FIM efficiency, and discharge rates to home. RESULTS: Patients with neoplastic SCC had a significantly (p < .01) shorter rehabilitation LOS than those with traumatic SCI (25.17 vs 57.46 days). No statistical significance was found in acute care LOS. Motor FIM scores on admission were higher in the neoplastic group, but discharge FIM scores and FIM change were significantly lower. Both groups had similar FIM efficiencies and community discharges. CONCLUSIONS: Patients with neoplastic SCC can achieve rates of functional gain comparable to those of their counterparts with traumatic SCI. While patients with traumatic SCI achieve greater functional improvement, patients with neoplastic SCC have a shorter rehabilitation LOS and can achieve comparable success with discharge to the community.

Age, outcome, and rehabilitation costs after paraplegia caused by traumatic injury of the thoracic spinal cord, conus medullaris, and cauda equina.

The object of this study was to investigate the relationships of age on neurologic and functional outcome, hospitalization length of stay (LOS), and hospital charges after spinal cord injury (SCI). At 20 medical centers, 2,169 consecutive adult patients with paraplegia SCI were assessed in acute care and inpatient rehabilitation. Outcome and treatment measures included the ASIA motor index score, functional independence measure, discharge to community ratio, LOS, and hospital charges. Age differences were examined by separating the sample into 11 age categories and conducting one-way analyses of variance on treatment, medical expense, and outcome measures that included the Functional Independence Measure (FIM) and ASIA motor index scores. Cramer's statistic was used to derive a chi-square value that indicated whether variables differed significantly in terms of age. Post-hoc Tukey tests were also performed. Age-related differences were found with multiple demographic variables. Significant differences between age categories were found with regard to the following treatment measures: ASIA motor index scores at acute-care admission and at discharge, rehabilitation LOS, inpatient rehabilitation hospitalization charges, total LOS, total hospitalization charges, FIM scores at inpatient rehabilitation admission and discharge, FIM change, and FIM efficiency. In conclusion, in patients with paraplegia, age appears to adversely affect functional outcome, rehabilitation LOS, and hospital costs. However, neurologic recovery as defined by the ASIA motor scores does not appear to be related to age.

The Saccharomyces cerevisiae protein YJR043C (Pol32) interacts with the catalytic subunit of DNA polymerase alpha and is required for cell cycle progression in G2/M.

We have analysed the YJR043c gene of Saccharomyces cerevisiae, previously identified by systematic sequencing. The deletion mutant (yjr043cdelta) shows slow growth at low temperature (15 degrees C), while at 30 degrees C and 37 degrees C the growth rate of mutant cells is only moderately affected. At permissive and nonpermissive temperatures, mutant cells were larger and showed a high proportion of large-budded cells with a single duplicated nucleus at or beyond the bud neck and a short spindle. This phenotype was even more striking at low temperature, the mutant cells becoming dumbbell shaped. All these phenotypes suggest a role for YJR043C in cell cycle progression in G2/M phase. In two-hybrid assays, the YJR043c gene product specifically interacted with Pol1, the catalytic subunit of DNA polymerase alpha. The pol1-1 /yjr043cdelta double mutant showed a more severe growth defect than the pol1-1 single mutant at permissive temperature. Centromeric plasmid loss rate elevated in yjr043cdelta. Analysis of the sequence upstream of the YJR043c ORF revealed the presence of an MluI motif (ACGCGT), a sequence associated with many genes involved in DNA replication in budding yeast. The cell cycle phenotype of the yjr043cdelta mutant, the evidence for genetic interaction with Pol1, the presence of an MluI motif upstream and the elevated rate of CEN plasmid loss in mutants all support a function for YJR043C in DNA replication.

Functional outcome after brain tumor and acute stroke: a comparative analysis.

OBJECTIVE: To compare the functional outcome, length of stay, and discharge disposition of patients with brain tumors and those with acute stroke. DESIGN: Case-controlled, retrospective study at a tertiary care medical center inpatient rehabilitation unit. SUBJECTS: Sixty-three brain tumor patients matched with 63 acute stroke patients according to age, sex, and location of lesion. MAIN OUTCOME MEASURES: The functional independence measure (FIM) was measured on admission and discharge. The FIM change and FIM efficiency were also calculated. The FIM was analyzed in three subsets: activities of daily living (ADL), mobility (MOB), and cognition (COG). Discharge disposition and rehabilitation length of stay were compared. RESULTS: Demographic variables of race, marital status, and payer source were comparable for the two groups. No significant difference was found between the brain tumor and stroke populations with respect to total admission FIM, total discharge FIM, change in total FIM, or FIM efficiency. The admission MOB-FIM was found to be higher in the brain tumor group (13.6 vs 11.1, p = .04), whereas the stroke group had a greater change in ADL-FIM score (10.8 vs 8.3, p = .03). The two groups had similar rates of discharge to community at greater than 85%. The tumor group had a significantly shorter rehabilitation length of stay than the stroke group (25 vs 34 days, p < .01). CONCLUSION: Brain tumor patients can achieve comparable functional outcome and rates of discharge to community and have a shorter rehabilitation length of stay than stroke patients.

Disruption of six novel yeast genes reveals three genes essential for vegetative growth and one required for growth at low temperature.

We describe here the construction of six deletion mutants and their basic phenotypic analysis. Six open reading frames (ORFs) from chromosome X, YJR039w, YJR041c, YJR043c, YJR046w, YJR053w and YJR065c, were disrupted by deletion cassettes with long (LFH) or short (SFH) flanking regions homologous to the target locus. The LFH deletion cassette was made by introducing into the kanMX4 marker module two polymerase chain reaction (PCR) fragments several hundred base pairs (bp) in size homologous to the promoter and terminator regions of a given ORF. The SFH gene disruption construct was obtained by PCR amplification of the kanMX4 marker with primers providing homology to the target gene. The region of homology to mediate homologous recombination was about 70 bp. Sporulation and tetrad analysis revealed that ORFs YJR041c, YJR046w and YJR065c are essential genes. Complementation tests by corresponding cognate gene clones confirmed this observation. The non-growing haploid segregants were observed under the microscope. The yjr041c delta haploid cells gave rise to microcolonies comprising about 20 to 50 cells. Most yjr046w delta cells were blocked after one or two cell cycles with heterogeneous bud sizes. The yjr065c delta cells displayed an unbudded spore or were arrested before completion of the first cell division cycle with a bud of variable size. The deduced protein of ORF YJR065c, that we named Act4, belongs to the Arp3 family of actin-related proteins. Three other ORFs, YJR039w, YJR043c and YJR053w are non-essential genes. The yjr043c delta cells hardly grew at 15 degrees C, indicating that this gene is required for growth at low temperature. Complementation tests confirmed that the disruption of YJR043c is responsible for this growth defect. In addition, the mating efficiency of yjr043c delta and yjr053w delta cells appear to be moderately affected.

Identification of ACT4, a novel essential actin-related gene in the yeast Saccharomyces cerevisiae.

Actin molecules are major cytoskeleton components of all eukaryotic cells. All conventional actins that have been identified so far are 374-376 amino acids in size and exhibit at least 70% amino acid sequence identity when compared with one another. In the yeast Saccharomyces cerevisiae, one conventional actin gene ACT1 and three so-called actin-related genes, ACT2, ACT3 and ACT5, have been identified. We report here the discovery of a new actin-related gene in this organism, which we have named ACT4. The deduced protein, Act4, of 449 amino acids, exhibits only 33.4%, 26.7%, 23.4% and 29.2% identity to Act1, Act2, Act3 and Act5, respectively. In contrast, it is 68.4% identical to the product of the Schizosaccharomyces pombe Act2 gene and has a similar level of identity to other Sch. pombe Act2 homologues. This places Act4 in the Arp3 family of actin-related proteins. ACT4 gene disruption and tetrad analysis demonstrate that this gene is essential for the vegetative growth of yeast cells. The act4 mutants exhibit heterogenous morphological phenotypes. We hypothesize that Act4 may have multiple roles in the cell cycle.

Analysis of a 62 kb DNA sequence of chromosome X reveals 36 open reading frames and a gene cluster with a counterpart on chromosome XI.

We have sequenced a 61.989 bp stretch located between genes RAD7 and FIP1 of Saccharomyces cerevisiae chromosome X. This stretch contains 36 open reading frames (ORFs) of at least 100 codons. Fourteen of these correspond to sequences previously published as HIT1, CDC8, YAP17, CBF1, NAT1, RPA12, CCT5, TOR1, RFC2, PEM2, CDC11, MIR1, STE18 and GRR1. The proteins deduced from four ORFs (YJR059w, YJR065c, YJR075w, YJR078w) have significant similarity to proteins of known function from yeast or other organisms, including S. cerevisiae serine/threonine-specific protein kinase. Schizosaccharomyces pombe Act2 protein, S. cerevisiae mannosyltransferase OCH1 protein and mouse indoleamine 2,3-dioxygenase, respectively. Four of the remaining 18 ORFs have similarity to proteins with unknown function, six are weakly similar to other known sequences, while another eight exhibit no similarity to any known sequence. In addition, three tRNA genes have been recognized. Three genes clustered within 22 kb (YJR059w, YJR061w and TOR1) have counterparts arranged within 15 kb on the left arm of chromosome XI.

Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X.

The complete nucleotide sequence of Saccharomyces cerevisiae chromosome X (745 442 bp) reveals a total of 379 open reading frames (ORFs), the coding region covering approximately 75% of the entire sequence. One hundred and eighteen ORFs (31%) correspond to genes previously identified in S. cerevisiae. All other ORFs represent novel putative yeast genes, whose function will have to be determined experimentally. However, 57 of the latter subset (another 15% of the total) encode proteins that show significant analogy to proteins of known function from yeast or other organisms. The remaining ORFs, exhibiting no significant similarity to any known sequence, amount to 54% of the total. General features of chromosome X are also reported, with emphasis on the nucleotide frequency distribution in the environment of the ATG and stop codons, the possible coding capacity of at least some of the small ORFs (<100 codons) and the significance of 46 non-canonical or unpaired nucleotides in the stems of some of the 24 tRNA genes recognized on this chromosome.

Analysis of a 42.5 kb DNA sequence of chromosome X reveals three tRNA genes and 14 new open reading frames including a gene most probably belonging to the family of ubiquitin-protein ligases.

We have sequenced a 42,500 bp stretch located on chromosome X of Saccharomyces cerevisiae between the genes MET3 and CDC8. This stretch contains 24 open reading frames (ORFs) of at least 100 amino acids. Ten of these correspond to previously published sequences, whereas of the 14 remaining ORFs, only one, GTD892, has significant similarity to proteins from yeast or other organisms. It may belong to the family of ubiquitin-protein ligases and be involved in the ubiquitin-dependent proteolytic pathway. In addition, three tRNA genes were recognized, two of which had not been hitherto localized.

A voltage-gated chloride channel in the yeast Saccharomyces cerevisiae.

We report the sequencing and identification on chromosome X of Saccharomyces cerevisiae of an open reading frame whose product, designated yClC-1, displays significant structural similarity to a voltage-gated Cl- channel family. This putative protein contains 13 hydrophobic domains very similar to transmembrane domains exhibited by known members of this family. Some amino acids in the domains and at the loops between them are well conserved among all members. This is the first voltage-gated Cl- channel described in the yeast S. cerevisiae. The identification of yClC-1 will facilitate the functional analysis of Cl- channels in general, and should also assist in the identification of other ClC genes in higher eukaryotes.

Revised nucleotide sequence of the COR region of yeast Saccharomyces cerevisiae chromosome X.

The COR region, a gene cluster located on chromosome X of Saccharomyces cerevisiae and including genes CYC1, UTR1, UTR3, OSM1, tRNA(Gly) and RAD7, was sequenced within the framework of the European Union genome systematic sequencing project. It was compared with previously published sequences to be found in GenBank under the acronym YSCCORA. While some of the discrepancies observed can be readily ascribed to polymorphism, others most probably result from sequencing errors. A revised version of the sequence of the COR cluster is given.