Detection of adenocarcinoma by urinary microsatellite analysis after augmentation cystoplasty

Augmentation cystoplasty is associated with an increased risk of bladder cancer development between 10 and 20 years after augmentation. Using microsatellite analysis, we analyzed urine obtained before surgical resection of the malignant lesion from a patient who developed invasive adenocarcinoma after augmentation cystoplasty. Loss of heterozygosity was identified in both urine and tumor samples from this patient. This observation suggests that microsatellite urine analysis may be useful as a monitoring tool for patients after augmentation cystoplasty.     

Antioxidant supplementation effects on low-density lipoprotein oxidation for individuals with type 2 diabetes mellitus.

OBJECTIVE: This study compared susceptibility to oxidation of low-density lipoproteins (LDL) of non-diabetic and diabetic (Type 2) men and examined the response of diabetic men to antioxidant supplementation (alpha-tocopherol, beta-carotene and ascorbate). RESEARCH DESIGN AND METHODS: Twenty adult non-diabetic and 20 diabetic men were recruited. Oxidation of LDL was assessed by four different assay systems, and the extent of oxidation was assessed by four different measurements. Diabetic men received eight weeks of placebo ("baseline"), twelve weeks of antioxidant supplements ("treated") and eight weeks of placebo ("post-treatment"). Supplements provided 24 mg of beta-carotene, 1000 mg of ascorbate and 800 IU of alpha-tocopherol daily. RESULTS: With Cu oxidation at 37 degrees C, thiobarbituric reactive substances (TBARS) formation was significantly higher (p=0.032) and loss of free amine groups was significantly greater (p=0.013) in the LDL from diabetic subjects than controls. Antioxidant supplementation of diabetic subjects significantly decreased all parameters of LDL oxidation with Cu at 30 degrees C and 37 degrees C. At 30 degrees C the lag phase increased from 55 to 129 minutes (p<0.0001); conjugated diene formation decreased from 1.23 to 0.62 OD units (p<0.0001); TBARS formation decreased from 78 to 33 nmoles MDA/mg LDL protein (p<0.0001); and free amine loss decreased from 41 to 12% (p<0.0001). With Cu oxidation at 37 degrees C, similar changes occurred. CONCLUSIONS: These studies indicate that the LDL from diabetic subjects are more susceptible to oxidation than LDL from non-diabetic subjects. Supplementation of diabetic subjects with antioxidant vitamins significantly decreases susceptibility of LDL to oxidation by Cu. These studies are consistent with epidemiological and intervention studies suggesting that antioxidant vitamin use significantly decreases risk for coronary heart disease.     

Successful closure of traumatic macular holes.

PURPOSE: To establish the efficacy of vitreoretinal surgery without the use of transforming growth factor-beta or autologous platelet concentrate in the repair of traumatic macular holes. METHODS: This retrospective review consisted of 16 eyes from 16 consecutive patients treated by five vitreoretinal surgeons at a single institution between 1993 and 1997. Intervention included pars plana vitrectomy with creation of posterior vitreous detachment, placement of 14% to 16% C3F8 gas, and postoperative face-down positioning. Ten eyes received intraoperative autologous plasmin to facilitate formation of posterior vitreous detachment. Main outcome measures were anatomic closure rate and visual outcome. RESULTS: Anatomic closure of the macular holes was achieved in 15 (94%) of 16 eyes, with an average follow-up of 7 months. Six (38%) eyes achieved visual acuity of 20/40 or better. Visual acuity improved by 2 or more lines in 11 (69%) of 16 eyes. The average preoperative logMAR-converted visual acuity of 20/175 improved to 20/60 postoperatively. CONCLUSION: Traumatic macular holes can be closed successfully with substantial visual recovery without the use of transforming growth factor-beta or platelet concentrate.     

Lorazepam for chronic catatonia: a randomized, double-blind, placebo-controlled cross-over study

Acute catatonic syndromes occurring in the context of various medical and neuropsychiatric conditions, including schizophrenia, have been shown to respond well to benzodiazepines (BZD). However, there have been no studies specifically designed to address the BZD treatment response of persistent catatonic states. Eighteen patients with clinically stable chronic schizophrenia, who also displayed enduring catatonic features, underwent a 12-week long, random assignment, double-blind, placebo-controlled cross-over trial with lorazepam (6 mg/day). A comprehensive assessment, including the subjects’ clinical and motor (catatonic as well as drug-induced movement disorders) condition, was performed at baseline and four weekly intervals thereafter. Pre-existing medication was kept constant throughout the study. Lorazepam had no effect on the subjects’catatonic signs and symptoms, suggesting that acute and chronic catatonic syndromes associated with schizophrenic illness might have a different neurobiological basis. Received: 25 May 1998/Final version: 22 September 1998     

Targeting Medicare in the Federal budget: an annual event?

When it came time to reduce the 1991 federal budget, it was not surprising that the budget cutters set their sights on Medicare to reduce the deficit. But why does Medicare appear to be such a major target at budget time, and when are "cuts" really cuts?     

Effects of a high-selenium yeast supplement on celecoxib plasma levels: a randomized phase II trial.

A combination of celecoxib and selenium was used in a randomized double-blind Phase II trial as a preliminary study to a multicenter Phase III colorectal cancer chemoprevention trial using these two agents together. The purpose of this trial was to determine whether high-selenium baker's yeast [(Saccharomyces cerevisiae) 200 microg once daily] in combination with celecoxib (400 mg once daily) altered the steady-state plasma concentration of celecoxib or produced clinically significant toxicities. Seventy-three healthy subjects (ages 40-75 years) were recruited to the 6-week study from the general local population and were randomized to either the celecoxib plus selenized baker's yeast group or the celecoxib plus placebo group after a 2-week run in period of celecoxib only. Blood samples were taken at baseline (to document that there was no evidence of celecoxib intake), after the 2-week run-in period on celecoxib to verify steady-state blood levels of this agent, and at end of study (4 weeks postrandomization). Toxicities were monitored at 2 weeks after initiation of celecoxib, at 4 weeks after initiation, and at the end of the study. Blood level concentrations of celecoxib did not differ between the two groups as determined by high-performance liquid chromatography analysis nor were there significant differences in blood chemistry values between the two groups. Subjects' self-report of general physical toxicities was uncommon and limited to National Cancer Institute toxicity grade 2 or less; however, 2 female participants (3%) were removed from the study medications because of grade 2 edema and significant weight gain after 2 and 2.5 weeks of celecoxib administration. In conclusion, high-selenium yeast and celecoxib can be taken at the described doses with minimum short-term negative effects. In future Phase III chemoprevention trials of celecoxib, weight gain should be carefully monitored, and participants should be made aware of this potential side effect before study entry.     

Survey on use of palliative radiotherapy in hospice care.

PURPOSE: Radiation oncologists and hospice professionals both provide end-of-life care for oncology patients, and little has been written about the interface between these two groups of specialists. Hospice professionals were surveyed to assess the perceived need for palliative radiotherapy in the hospice setting, to investigate factors that limit the access of hospice patients to radiotherapy, and to suggest areas of future collaboration on education, research, and patient advocacy. PATIENTS AND METHODS: Members of the National Hospice and Palliative Care Organization (NHPCO) and American Society for Therapeutic Radiology and Oncology jointly authored a questionnaire to investigate the beliefs of hospice professionals toward the use of radiotherapy for oncology patients in hospice. The questionnaire was distributed to all NHPCO member institutions, and the results were compiled and statistically analyzed. RESULTS: Four hundred eighty of more than 1,800 surveyed facilities responded to the questionnaire. The findings suggest that the majority of hospice professionals feel that radiotherapy is important in palliative oncology and that radiotherapy is widely available in the United States. Yet less than 3% on average of hospice patients served by hospices responding to the survey actually received radiotherapy in 2002. The most common barriers to radiotherapy in hospice care include radiotherapy expense, transportation difficulties, short life expectancy, and educational deficiencies between the specialties. CONCLUSION: Multiple barriers act to limit the use of palliative radiotherapy in hospice care. Finding ways to surmount these obstacles will provide opportunity for improvement in the end-of-life care of cancer patients.     

Nonsteroidal anti-inflammatory drug use associated with reduced incidence of adenocarcinomas of the esophagus and gastric cardia that overexpress cyclin D1: a population-based study.

This study was undertaken to determine whether selected risk factors for esophageal and gastric cancer are associated with tumors that overexpress cyclin D1. Archived tumor tissue was available for 630 esophageal and gastric cancer patients who participated in a population-based case-control study. Patients were categorized into case groups based on whether protein overexpression of the cyclin D1 gene, as assessed by immunohistochemistry, was present (cyclin D1+, n = 285) or not (cyclin D1-, n = 345) in the tumor. The distribution of risk factors in each of these case groups was then compared with the distribution among the 695 controls. Multivariate-adjusted odds ratios (OR) for esophageal adenocarcinoma were reduced in relation to use of aspirin and other nonsteroidal anti-inflammatory drug (NSAID) use but only among patients with cyclin D1+ tumors (0.45, 95% confidence interval [CI] = 0.26, 0.79) and not among those with cyclin D1- tumors (1.12, 95% CI = 0.67, 1.86). A similar pattern was observed for gastric cardia adenocarcinomas. In contrast, ORs for esophageal squamous cell carcinoma and noncardia gastric adenocarcinomas in relation to NSAID use were reduced, regardless of cyclin D1 status. ORs did not vary with cyclin D1 status in relation to alcohol, body size, or cigarette smoking, with the following exception; for noncardia gastric adenocarcinomas the cyclin D1- tumors showed a 2-fold elevation in the OR with ever smoking. These data suggest that the reduction in risk associated with NSAID use may be restricted to those esophageal and gastric cardia adenocarcinomas that overexpress cyclin D1.     

Evaluation of biologic end points and pharmacokinetics in patients with metastatic breast cancer after treatment with erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor.

PURPOSE: To evaluate changes in epidermal growth factor receptor (EGFR) phosphorylation and its downstream signaling in tumor and surrogate tissue biopsies in patients with metastatic breast cancer treated with erlotinib, an EGFR tyrosine kinase inhibitor, and to assess relationships between biomarkers in tumor and normal tissues and between biomarkers and pharmacokinetics. PATIENTS AND METHODS: Eighteen patients were treated orally with 150 mg/d of erlotinib. Ki67, EGFR, phosphorylated EGFR (pEGFR), phosphorylated mitogen-activated protein kinase (pMAPK), and phosphorylated AKT (pAKT) in 15 paired tumor, skin, and buccal mucosa biopsies (at baseline and after 1 month of therapy) were examined by immunohistochemistry and analyzed quantitatively. Pharmacokinetic sampling was also obtained. RESULTS: The stratum corneum layer and Ki67 in keratinocytes of the epidermis in 15 paired skin biopsies significantly decreased after treatment (P = .0005 and P = .0003, respectively). No significant change in Ki67 was detected in 15 tumors, and no responses were observed. One was EGFR-positive and displayed heterogeneous expression of the receptor, and 14 were EGFR-negative. In the EGFR-positive tumor, pEGFR, pMAPK, and pAKT were reduced after treatment. Paradoxically, pEGFR was increased in EGFR-negative tumors post-treatment (P = .001). Although markers were reduced in surrogate and tumor tissues in the patient with EGFR-positive tumor, no apparent associations were observed in patients with EGFR-negative tumor. CONCLUSION: Erlotinib has inhibitory biologic effects on normal surrogate tissues and on an EGFR-positive tumor. The lack of reduced tumor proliferation may be attributed to the heterogeneous expression of receptor in the EGFR-positive patient and absence of target in this cohort of heavily pretreated patients.