Comorbidity and functional status are independent in older cancer patients

PURPOSE: Comorbidity is a frequent and often therapeutically limiting problem in older cancer patients. However, to date, there is no standard measure of the comorbidity burden available for these patients. We tested the performance of two comorbidity scales and their relationship with functional status. PATIENTS AND METHODS: The Cumulative Illness Rating Scale-Geriatric (CIRS-G) was compared with the Charlson scale in 203 patients who received a comprehensive geriatric assessment (CGA) in our Senior Adult Oncology Program (SAOP). Study end points were variability, reliability, correlation with Eastern Cooperative Oncology Group (ECOG) performance status (PS), Activities of Daily Living (ADL), and Instrumental Activities of Daily Living (IADL). The relative weight of comorbidity versus tumor stage in the correlations with functional status was assessed. RESULTS: Median age was 75 years (range, 63 to 91). Sixty-four percent of patients scored 0 on the Charlson scale versus 6% on the CIRS-G. The correlation between the Charlson and CIRS-G was fair (p = 0.25 to 0.39). CIRS-G grade 3/4 had a fair correlation with ADL (p = 0.27). Otherwise, there was low or no correlation between comorbidity and functional status across the measures. Tumor stage was not correlated with functional status either. Correlation of ECOG PS with ADL (p = 0.51)c and IADL (p = 0.61) was moderate. Interrater and test-retest correlations were good or very good for both the Charlson and CIRS-G. CONCLUSION: Comorbidity needs to be assessed independently from functional status. Both the Charlson and CIRS-G scales are reliable tools for use in trials of older cancer patients. Both can be tested in further studies as predictors of outcomes such as toxicity of treatment, changes in functional status, or survival.     

Disulfide bond structure determination and biochemical analysis of glycoprotein C from herpes simplex virus

A biochemical analysis of glycoprotein C (gC of herpes simplex virus was undertaken to further characterize the structure of the glycoprotein and to determine its disulfide bond arrangement. We used three recombinant forms of gC, gC1(457t), gC1(delta33-123t), and gC2(426t), each truncated prior to the transmembrane region. The proteins were expressed and secreted by using a baculovirus expression system and have been shown to bind to monoclonal antibodies which recognize discontinuous epitopes and to complement component C3b in a dose-dependent manner. We confirmed the N-terminal residues of each mature protein by Edman degradation and confirmed the internal deletion in gC1(delta33-123t). The molecular weight and extent of glycosylation of gC1 (457t), gC1(delta33-123t), and gC2(426t) were determined by treating each protein with endoglycosidases and then subjecting it to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometric analysis. The data indicate that eight to nine of the predicted N-linked oligosaccharide sites on gC1(457t) are occupied by glycans of approximately 1,000 Da. In addition, O-linked oligosaccharides are present on gC1(457t), primarily localized to the N-terminal region (amino acids [aa] 33 to 123) of the protein. gC2(426t) contains N-linked oligosaccharides, but no O-linked oligosaccharides were detected. To determine the disulfide bond arrangement of the eight cysteines of gC1(457t),the protein was cleaved with cyanogen bromide. SDS-PAGE analysis followed by Edman degradation identified three cysteine-containing fragments which are not connected by disulfide linkages. Chemical modification of cysteines combined with matrix-assisted laser desorption ionization mass spectrometry identified disulfide bonds between cysteine 1 (aa 127) and cysteine 2 (aa 144) and between cysteine 3 (aa 286) and cysteine 4 (aa 347). Further proteolysis of the cyanogen bromide-generated fragment containing cysteine 5 through cysteine 8, combined with mass spectrometry and Edman degradation, showed that disulfide bonds link cysteine 5 (aa 386) to cysteine 8 (aa 442) and cysteine 6 (aa 390) to cysteine 7 (aa 419). A similar disulfide bond arrangement is postulated to exist in gC homologs from other herpesviruses.     

Urinary proton magnetic resonance studies of early ifosfamide-induced nephrotoxicity and encephalopathy

Ifosfamide is an oxazophosphorine widely used in the treatment of cancer in children and adults. Nephrotoxicity and neurotoxicity are major side effects. The aim of this study was to use high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy of urine to identify novel biochemical markers of ifosfamide-induced toxicity. Urine samples were collected from 10 nonencephalopathic patients (who had not previously received nephrotoxic chemotherapy) immediately prior to the first ifosfamide dose and at timed intervals for up to four treatment cycles. The findings were compared with those for urine samples collected from five patients during acute encephalopathic episodes. 1H NMR urinalysis identified a series of characteristic time-related changes in the excretion profiles of low molecular weight endogenous metabolites during ifosfamide therapy. These changes included a decreased excretion of hippurate and an increased excretion of glycine, histidine, glucose, lactate, and trimethylamine-N-oxide. Two nonencephalopathic patients had marked but transient glutaric or adipic aciduria during the second cycle of ifosfamide treatment. Urinary retinol-binding protein rose acutely after each treatment cycle but usually returned to baseline levels. Maximum renal toxicity was observed by the fourth treatment cycle. The ratio of the urinary excretion of the uroprotectant mesna (active form) to dimesna (inactive form) correlated with the degree of renal toxicity. For the encephalopathic patients, the ifosfamide-induced changes in the urinary low molecular weight metabolite profile were similar to those for the nonencephalopathic group. In contrast to previous reports, none of the encephalopathic group developed glutaric aciduria, and i.v. methylene blue did not reverse neurotoxicity in the two patients who received it. The results suggest that ifosfamide nephrotoxicity involves both cortical and medullary regions of the nephron and that the urinary mesna:dimesna ratio may be important in assessing the degree of cytoprotection. This study demonstrates that 1H NMR can provide novel biochemical information on ifosfamide-induced toxicity and will be of value in the optimization of ifosfamide therapy.     

The thiazide-sensitive Na-Cl cotransporter is an aldosterone-induced protein

Although the collecting duct is regarded as the primary site at which mineralocorticoids regulate renal sodium transport in the kidney, recent evidence points to the distal convoluted tubule as a possible site of mineralocorticoid action. To investigate whether mineralocorticoids regulate the expression of the thiazide-sensitive Na-Cl cotransporter (TSC), the chief apical sodium entry pathway of distal convoluted tubule cells, we prepared an affinity-purified, peptide-directed antibody to TSC. On immunoblots, the antibody recognized a prominent 165-kDa band in membrane fractions from the renal cortex but not from the renal medulla. Immunofluorescence immunocytochemistry showed TSC labeling only in distal convoluted tubule cells. Semiquantitative immunoblotting studies demonstrated a large increase in TSC expression in the renal cortex of rats on a low-NaCl diet (207 +/- 21% of control diet). Immunofluorescence localization in tissue sections confirmed the strong increase in TSC expression. Treatment of rats for 10 days with a continuous subcutaneous infusion of aldosterone also increased TSC expression (380 +/- 58% of controls). Furthermore, 7-day treatment of rats with an orally administered mineralocorticoid, fludrocortisone, increased TSC expression (656 +/- 114% of controls). We conclude that the distal convoluted tubule is an important site of action of the mineralocorticoid aldosterone, which strongly up-regulates the expression of TSC.     

Effects of gallstone solvents on commonly used catheters

PURPOSE: To determine what interaction and effect different cholesterol gallstone solvents have on catheters used for gallstone chemolysis. MATERIALS AND METHODS: Five types of catheters used for biliary procedures were chosen: polyethylene, Percuflex, silicon, Silitek, and polyurethane. The solvents chosen were methyl tert-butyl ether, ethyl propionate, isopropyl acetate, and N-propyl acetate. After incubation of the catheters in the solvents for 72 hours, they were air dried. Weight and area changes were determined for each catheter. Additionally, carbon-13 nuclear magnetic resonance (NMR) spectroscopy was performed for analysis of composition changes. RESULTS: Three catheters--silicone, Silitek, and polyurethane--showed changes in their physical characteristics that would make them less desirable for stone chemolysis. The silicone catheter showed changes in elastic texture as well as marked weight reduction. The Silitek and polyurethane catheters had similar, but less dramatic changes. C-13 NMR analysis of collected solvents showed that commonly used plasticizers were leached out of some catheters. CONCLUSION: These results suggest that all catheters are not suitable for use with all solvents. The choice of catheter should be made based on the solvent in use. The polyethylene catheter performed best under the conditions and endpoints used in this study.     

Outpatient hysterectomy: determinants of discharge and rehospitalization in 133 patients

OBJECTIVE: This study examines our continuing experience in performing vaginal hysterectomies and laparoscopy-assisted vaginal hysterectomies with an outpatient protocol. The purpose was to review factors associated with discharge and hospitalization. STUDY DESIGN: Surgical records from all women entering our previously reported outpatient hysterectomy protocol were reviewed. Demographics, surgical indications, intraoperative data, and postoperative data were studied, and their associations with patient discharge and hospitalization were determined. Specific attention was directed to complications. RESULTS: The study group consisted of 133 women. Twelve women (9.0%) were not discharged from the hospital and 5 (3.8%) required readmission. Surgical indications, the type of hysterectomy, and the requirement for pain medication revealed no association with hospitalization. The occurrence of an intraoperative complication (p < 0.000), the need for transfusion (p = 0.043), and postoperative antiemetics (p = 0.013) were statistically associated with hospitalization. In addition, low hematocrit values and elevated temperatures on the first and second postoperative days were associated with hospitalization. CONCLUSION: Long-term experience with outpatient hysterectomy reveals a hospitalization rate of 12.8%. Complications, blood loss, elevated temperatures, and postoperative nausea are the major determinants of patient discharge and hospitalization. Readmission rates continue to remain low.