Long-term outcome for lymph node-positive prostate cancer.

Although the number of men with lymph node-positive prostate cancer has declined, it is still significant and the challenge remains on how best to treat these patients. Only long-term follow-up can give a true indication of the outcome in prostate cancer. We evaluated our experience in treating lymph node-positive prostate cancer with a median follow-up of 10.2 years. The overall 5-year survival was 78% and the 10-year survival was 56%. Length of tumor control depends on the type of treatment given. Adding androgen ablation improves the duration of control dramatically, although optimal timing is still uncertain.

Long-term follow-up of radiotherapy for prostate cancer.

PURPOSE: To determine the long-term outcome of radiotherapy for prostate cancer. METHODS AND MATERIALS: A total of 136 consecutive patients with prostate cancer underwent primary radiotherapy. All but 4 patients received 6000 cGy to the prostate. The minimal follow-up was 22.9 years. RESULTS: Of the 136 patients, 93 had Stage B (T2), 9 Stage A (T1), and 34 Stage C (T3). Sixty-nine percent of the patients developed recurrence, and 51% of all patients died of prostate cancer. The recurrences developed at a steady state throughout the length of follow-up. One half the recurrences occurred after 10 years, and recurrence was still observed >20 years after treatment. The survival rate at 5, 10, 15, 20, and 25 years was 81%, 59%, 37%, 16%, and 10%, respectively. The recurrence-free survival rate at 25 years was 17%. The median survival for Grade 3-4 patients was 6.3 years and for Grade 1-2 patients was 13.0 years. The median survival for those with T1 tumors was 12.9 years; T2 tumors, 12.4 years; and T3 tumors, 9.5 years. CONCLUSION: Despite favorable early results, with long-term follow-up, patients continued to experience prostate cancer recurrence. Unless they died an intercurrent death, they were highly likely to develop recurrence and die of prostate cancer. The conclusions from treatment studies with <15 years of follow-up should be viewed as preliminary.

Long-term follow-up of radical retropubic prostatectomy for prostate cancer.

OBJECTIVES: The ultimate outcome of patients after radical prostatectomy is often predicted from statistical projections of short-term follow-up. Only actual long-term follow-up can demonstrate true outcome. METHODS: One hundred thirty-one patients underwent retropubic prostatectomy for clinically organ confined prostate cancer and have been followed for a minimum of 22.5 years. Preoperatively, all but 12 had clinically palpable cancer. RESULTS: Overall survival in these patients was similar to an age-matched population, with 65% alive at 15 years, and 23% alive at 25 years. Thirty-seven percent of the patients recurred and 24% of all the patients died of prostate cancer. For patients with pathologically organ confined disease, 27% recurred, while those with extension outside the gland or positive nodes had an 83% recurrence rate. Although, the median time to recurrence was 7 years, recurrences occurred at a steady-state throughout the length of follow-up. Patients with higher grade tumors, even if organ confined, were significantly more likely to recur. CONCLUSIONS: In a cohort of patients treated with radical prostatectomy for predominantly palpable disease, long-term follow-up (79% deceased) reveals that 37% will recur and 24% will die of prostate cancer. Almost half the recurrences occurred after 10 years, indicating that reports with shorter follow-up will underestimate the recurrence rate.

Red blood cell transfusion practices in very low birth weight infants in 1990s postsurfactant era.

The purposes of this study are (1) to evaluate the practice of red blood cell transfusions in very low birth weight (VLBW) infants (between 501 to 1500 g) during the postsurfactant era of the 1990s; and (2) to evaluate if there is a decreasing trend in red cell transfusions in the 1990s. Database and medical records of VLBW infants admitted to the neonatal intensive care unit (NICU) between January 1990 and December 1995 at Scott & White Clinic, Temple, Texas, were reviewed. Five hundred twenty-seven infants were admitted to the NICU, excluding 5 infants that were transferred out for possible cardiac surgery or for other reasons. Fifty one (9.7%) of these infants died prior to discharge. Hence, data from 476 survivors were reviewed for red blood cell (RBC) transfusions. Transfusions were given at the discretion of the attending neonatologist. None of the infants received erythropoietin. Of the 476 infants, 289 (61%) received RBC transfusions during the hospital stay, with 2.7+/-3.6 transfusions per infant with a volume of 40.5+/-50.4 mL/kg. Smaller infants required significantly more transfusions compared to larger infants when divided into 250-g subgroups. No statistically significant difference was noted in the number of RBC transfusions per infant or number of infants transfused during the 6-year period from year to year. We conclude that VLBW infants in the 1990s postsurfactant era required 2.7 RBC transfusions per infant, on average, with the smallest infants requiring the most transfusions. These data will be helpful to counsel mothers in preterm labor regarding the need of transfusions for each birth weight category. Red cell transfusion practice has not changed over this 6-year period in the 1990s. Additional measures such as erythropoietin or even stricter transfusion criteria may be necessary to decrease transfusions further. However, safety of such measures should be carefully evaluated.

Characterization of an intestinal epithelial cell receptor recognized by the Cryptosporidium parvum sporozoite ligand CSL.

The protozoan parasite Cryptosporidium parvum is a leading cause of diarrhea in humans and neonatal calves. The absence of approved parasite-specific drugs, vaccines, and immunotherapies for cryptosporidiosis relates in part to limited knowledge on the pathogenesis of zoite attachment and invasion. We recently reported that the C. parvum apical complex glycoprotein CSL contains a zoite ligand for intestinal epithelial cells which is defined by monoclonal antibody (MAb) 3E2. In the present study, the host cell receptor for CSL was characterized. For these studies, a panel of epithelial and mesenchymal cell lines was examined for permissiveness to C. parvum and the ability to bind CSL. Cells of epithelial origin were significantly more permissive and bound significantly greater quantities of CSL than cells of mesenchymal origin. Caco-2 intestinal cells were selected from the epithelial panel for further characterization of the CSL receptor. Immunoelectron microscopy demonstrated that CSL bound initially to the surface of Caco-2 cells and was rapidly internalized. The molecule bound by CSL was identified as an 85-kDa Caco-2 cell surface protein by radioimmunoprecipitation and CSL affinity chromatography. Sporozoite incubation with the isolated 85-kDa protein reduced binding of MAb 3E2. Further, attachment and invasion were significantly inhibited when sporozoites were incubated with the 85-kDa protein prior to inoculation onto Caco-2 cells. These observations indicate that the 85-kDa protein functions as a Caco-2 cell receptor for CSL. CSL also bound specifically to intestinal epithelium from calves, indicating receptor expression in a second important host species. Molecular characterization of the CSL receptor may lead to novel avenues for disrupting ligand-receptor interactions in the pathogenesis of C. parvum infection.

Randomized, multicenter comparison of oral granisetron and oral ondansetron for emetogenic chemotherapy.

STUDY OBJECTIVES: To compare the antiemetic effectiveness and safety of oral granisetron plus dexamethasone with those of oral ondansetron plus dexamethasone administered before emetogenic chemotherapy. DESIGN: Randomized, prospective, multicenter, open-label study. SETTINGS: University-teaching hospital and veterans health care system. PATIENTS: Sixty-one chemotherapy-naïve patients scheduled to receive emetogenic antineoplastic agents. INTERVENTION: A single-dose oral granisetron 1 mg and dexamethasone 12 mg or single-dose oral ondansetron 16 mg and dexamethasone 12 mg was administered before chemotherapy. MEASUREMENTS AND RESULTS: Twenty-four hours after administration patients were contacted to assess nausea, emesis, and adverse events. There were no statistical differences in frequency of nausea or emesis between groups. Seventy-six percent and 82% of patients receiving ondansetron and granisetron, respectively, experienced no emesis 24 hours after chemotherapy. Complete protection from nausea occurred in 58% and 46% of patients receiving the drugs, respectively. Adverse events were similar between groups. CONCLUSION: Oral granisetron 1 mg and ondansetron 16 mg plus dexamethasone are safe and effective in preventing nausea and vomiting related to emetogenic chemotherapy.

Characterization and formulation of multiple epitope-specific neutralizing monoclonal antibodies for passive immunization against cryptosporidiosis.

The coccidian parasite Cryptosporidium parvum causes diarrhea in humans, calves, and other mammals. Neither immunization nor parasite-specific pharmaceuticals that are consistently effective against this organism are available. While polyclonal antibodies against whole C. parvum reduce infection, their efficacy and predictability are suboptimal. We hypothesized that passive immunization against cryptosporidiosis could be improved by using neutralizing monoclonal antibodies (MAbs) targeting functionally defined antigens on the infective stages. We previously reported that the apical complex and surface-exposed zoite antigens CSL, GP25-200, and P23 are critical in the infection process and are therefore rational targets. In the present study, a panel of 126 MAbs generated against affinity-purified CSL, GP25-200, and P23 was characterized to identify the most efficacious neutralizing MAb formulation targeting each antigen. To identify neutralizing MAbs, sporozoite infectivity following exposure to individual MAbs was assessed by enzyme-linked immunosorbent assay. Of 126 MAbs evaluated, 47 had neutralizing activity. These were then evaluated individually in oocyst-challenged neonatal mice, and 14 MAbs having highly significant efficacy were identified for further testing in formulations. Epitope specificity assays were performed to determine if candidate MAbs recognized the same or different epitopes. Formulations of two or three neutralizing MAbs, each recognizing distinct epitopes, were then evaluated. A formulation of MAbs 3E2 (anti-CSL [alphaCSL]), 3H2 (alphaGP25-200), and 1E10 (alphaP23) provided highly significant additive efficacy over that of either individual MAbs or combinations of two MAbs and reduced intestinal infection by 86 to 93%. These findings indicate that polyvalent neutralizing MAb formulations targeting epitopes on defined antigens may provide optimal passive immunization against cryptosporidiosis.

Hormone withdrawal symptoms in oral contraceptive users.

OBJECTIVE: To measure the timing, frequency, and severity of hormone-related symptoms in oral contraceptive (OC) users, specifically to compare active-pill with hormone-free intervals. METHODS: Using daily diaries, women recorded pelvic pain, bleeding, headaches, analgesic use, nausea or vomiting, bloating or swelling, and breast tenderness during active-pill intervals and hormone-free intervals. Participants either had no prior OC use, had taken OCs and were restarting, or had been taking OCs continuously for 12 months or longer. RESULTS: Two hundred sixty-two women, 26 with no previous OC use, 43 prior users, and 193 current users, provided daily records of hormone-related symptoms. Subjects with no prior OC use and prior users restarting were similar in no recent OC use, and because of the small sample, they were pooled for analysis as new-start OC users. Current users had patterns of symptoms that were more frequent during hormone-free intervals than during the three active-pill weeks. These included pelvic pain (70% versus 21%, P < .001), headaches (70% versus 53%, P < .001), use of pain medication (69% versus 43%, P < .001), bloating or swelling (58% versus 19%, P < .001), and breast tenderness (38% versus 16%, P < .001). Similar patterns were seen in new-start OC users after the first cycle. Among new-start OC users, menstrual flow patterns, headache, bloating or swelling, and breast-tenderness symptoms decreased during the three cycles to approach those levels of current users. CONCLUSION: Almost all symptoms assessed were significantly worse during the 7-day hormone-free interval than during the 21 days of hormone-containing pills.

Psychosocial and demographic factors related to health behaviors in the 1st trimester.

OBJECTIVE: To explore the relationship of psychosocial and demographic variables to health behaviors in early pregnancy. DESIGN: First trimester findings presented from a prospective study of weight gain in pregnancy. SETTING: A comprehensive health care system in central Texas. PARTICIPANTS: 114 pregnant women (75% white, 13% African American, 10% Hispanic, 2% Asian) of 12 weeks gestation or less. OUTCOME MEASURE: Self-Care Inventory, which includes diet/eating, substance abuse, recklessness, hygiene-related practices, sleep/rest, and exercise behaviors. RESULTS: In regression analysis the final model of demographic and psychosocial variables showed that higher depressive symptoms, lower internal locus of control for fetal health, and lower family income were related to poorer health behaviors in the 1st trimester of pregnancy. CONCLUSIONS: Health behaviors in early pregnancy may be affected by psychosocial factors such as depressive symptoms. Greater emphasis should be given to such factors in research and prenatal assessments.

Cryptosporidium parvum apical complex glycoprotein CSL contains a sporozoite ligand for intestinal epithelial cells.

Cryptosporidiosis, caused by the apicomplexan parasite Cryptosporidium parvum, has become a well-recognized diarrheal disease of humans and other mammals throughout the world. No approved parasite-specific drugs, vaccines, or immunotherapies for control of the disease are currently available, although passive immunization with C. parvum-specific antibodies has some efficacy in immunocompromised and neonatal hosts. We previously reported that CSL, an approximately 1,300-kDa conserved apical glycoprotein of C. parvum sporozoites and merozoites, is the antigenic species mechanistically bound by neutralizing monoclonal antibody 3E2 which elicits the circumsporozoite precipitate (CSP)-like reaction and passively protects against C. parvum infection in vivo. These findings indicated that CSL has a functional role in sporozoite infectivity. Here we report that CSL has properties consistent with being a sporozoite ligand for intestinal epithelial cells. For these studies, native CSL was isolated from whole sporozoites by isoelectric focusing (IEF) following observations that the approximately 1,300-kDa region containing CSL as seen by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was comprised of approximately 15 molecular species (pI 3 to 10) when examined by two-dimensional (2-D) electrophoresis and silver staining. A subset of six approximately 1,300-kDa species (pI 4.0 to 6.5) was specifically recognized by 3E2 in 2-D Western immunoblots of IEF-isolated CSL. Isolated native CSL bound specifically and with high affinity to permissive human intestinal epithelial Caco-2 cells in a dose-dependent, saturable, and self-displaceable manner. Further, CSL specifically bound to the surface of live Caco-2 cells inhibited sporozoite attachment and invasion. In addition, sporozoites having released CSL after incubation with 3E2 and occurrence of the CSP-like reaction did not attach to and invade Caco-2 cells. These findings indicate that CSL contains a sporozoite ligand which facilitates attachment to and invasion of Caco-2 cells and, further, that ligand function may be disrupted by CSL-reactive monoclonal antibody. We conclude that CSL is a rational target for passive or active immunization against cryptosporidiosis.

Evidence of thymus-independent local and systemic antibody responses to Cryptosporidium parvum infection in nude mice.

Differences in susceptibility to persistent cryptosporidial infection between two strains of adult athymic nude mice prompted us to investigate the immune mechanism(s) that may control resistance to infection in these T-cell-deficient mice. We studied fecal oocyst shedding, serum and fecal parasite-specific antibody responses, and fecal immunoglobulin levels in athymic C57BL/6J nude and athymic BALB/cJ nude mice following oral inoculation with Cryptosporidium parvum oocysts at 8 to 9 weeks of age. C57BL/6J nude mice had significantly higher fecal parasite-specific immunoglobulin A (IgA) (days 27, 31, 35, and 42 postinoculation) and IgM (days 10, 17, 24, 28, 31, 38, 42, and 48 postinoculation) levels than BALB/cJ nude mice (P < 0.05) and significantly higher serum parasite-specific IgA levels at 63 days postinoculation (P < 0.03). Moreover, C57BL/6J nude mice shed significantly fewer C. parvum oocysts than BALB/cJ nude mice from days 52 to 63 postinoculation (P < 0.05). In contrast, BALB/cJ nude mice had higher levels of non-parasite-specific IgA (days 38 to 63 postinoculation) and IgM (days 24, 35, 38, and 52 postinoculation) than C57BL/6J nude mice in feces (P < 0.05). These data suggest that parasite-specific fecal antibodies may be associated with resistance to C. parvum in C57BL/6J nude mice.

Cryptosporidium parvum sporozoite pellicle antigen recognized by a neutralizing monoclonal antibody is a beta-mannosylated glycolipid.

The protozoan parasite Cryptosporidium parvum is an important cause of diarrhea in humans, calves, and other mammals worldwide. No approved vaccines or parasite-specific drugs are currently available for the control of cryptosporidiosis. To effectively immunize against C. parvum, identification and characterization of protective antigens are required. We previously identified CPS-500, a conserved, neutralization-sensitive antigen of C. parvum sporozoites and merozoites defined by monoclonal antibody 18.44. In the present study, the biochemical characteristics and subcellular location of CPS-500 were determined. CPS-500 was chloroform extractable and eluted with acetone and methanol in silicic acid chromatography, consistent with being a polar glycolipid. Following chloroform extraction and silicic acid chromatography, CPS-500 was isolated by high-pressure liquid chromatography for glycosyl analysis, which indicated the presence of mannose and inositol. To identify which component of CPS-500 comprised the neutralization-sensitive epitope recognized by 18.44, the ability of the monoclonal antibody to bind CPS-500 treated with proteases, or with alpha- or beta-glycosidases, was determined. Monoclonal antibody 18.44 did not bind antigen treated with beta-D-mannosidase but did bind antigen treated with alpha-D-mannosidase, other alpha- or beta-glycosidases, or a panel of proteases. These data indicated that the target epitope was dependent on terminal beta-D-mannopyranosyl residues. By immunoelectron microscopy, 18.44 binding was localized to the pellicle and an intracytoplasmic tubulovesicular network in sporozoites. Monoclonal antibody 18.44 also bound to antigen deposited and released onto substrate over the course travelled by gliding sporozoites and merozoites. Surface localization, adhesion and release during locomotion, and neutralization sensitivity suggest that CPS-500 may be involved in motility and invasion processes of the infective zoite stages.

Role of immunoglobulin A monoclonal antibodies against P23 in controlling murine Cryptosporidium parvum infection.

Cryptosporidium parvum is an important diarrhea-causing protozoan parasite of immunocompetent and immunocompromised hosts. Immunoglobulin A (IgA) has been implicated in resistance to mucosal infections with bacteria, viruses, and parasites, but little is known about the role of IgA in the control of C. parvum infection. We assessed the role of IgA during C. parvum infection in neonatal mice. IgA-secreting hybridomas were developed by using Peyer's patch lymphocytes from BALB/c mice which had been orally inoculated with viable C. parvum oocysts. Six monoclonal antibodies (MAbs) were selected for further study based on indirect immunofluorescence assay reactivity with sporozoite and merozoite pellicles and the antigen (Ag) deposited on glass substrate by gliding sporozoites. Each MAb was secreted in dimeric form and recognized a 23-kDa sporozoite Ag in Western immunoblots. The Ag recognized comigrated in sodium dodecyl sulfate-polyacrylamide gel electrophoresis with P23, a previously defined neutralization-sensitive zoite pellicle Ag. MAbs were evaluated for prophylactic or therapeutic efficacy against C. parvum, singly and in combinations, in neonatal BALB/c mice. A combination of two MAbs given prophylactically prior to and 12 h following oocyst challenge reduced the number of intestinal parasites scored histologically by 21.1% compared to the numbers in mice given an isotype-matched control MAb (P < 0.01). Individual MAbs given therapeutically in nine doses over a 96-h period following oocyst challenge increased efficacy against C. parvum infection. Four MAbs given therapeutically each reduced intestinal infection 34.4 to 42.2% compared to isotype-matched control MAb-treated mice (P < 0.05). One MAb reduced infection 63.3 and 72. 7% in replicate experiments compared to isotype-matched control MAb-treated mice (P < 0.0001). We conclude that IgA MAbs directed to neutralization-sensitive P23 epitopes may have utility in passive immunization against murine C. parvum infection.

Use of age-specific normal ranges for serum prostate-specific antigen.

BACKGROUND: The traditional normal range for prostate-specific antigen has been 0.0 to 4.0 ng/mL. Two different age-specific normal ranges have been proposed, one by Oesterling et al and the other generated by the Prostate Cancer Awareness Week experience. METHODS: We studied 213 consecutive cases of biopsy-proven prostate adenocarcinoma to evaluate age-specific normal ranges for prostate-specific antigen. We examined each patient's age, stage of disease, and serum concentration of prostate-specific antigen at the time of diagnosis. The three normal ranges were applied to each case. RESULTS: The patients ranged in age from 45 to 87 years. At all stages of disease, more patients had elevated serum prostate-specific antigen values using the traditional normal range as opposed to either age-specific normal range. These discrepancies were most obvious for stage II disease, in which 93 of 119 cases (78%) were elevated according to the traditional normal range versus 78 of 119 cases (66%) according to the Oesterling et al range and 80 of 119 cases (67%) according to the range defined during Prostate Cancer Awareness Week. For patients aged 40 to 59 years, all three normal ranges provided identical results (18 of 22 [82%] cancers detected). CONCLUSIONS: Use of either age-specific normal range would have missed more than 10% of stage II prostate adenocarcinomas in patients over the age of 60 years. This indicates that caution should be exercised when applying age-adjusted normal ranges for serum concentrations of prostate-specific antigen in patients of that age group.

Significance of nondiagnostic fine-needle aspiration of the thyroid.

BACKGROUND: Fine-needle aspiration biopsy (FNAB) has been shown to be rapid and cost effective in the evaluation of thyroid nodules. The significance of nondiagnostic (unsatisfactory) FNAB is uncertain, however. METHODS: We reviewed 345 consecutive thyroid FNABs and identified 59 patients with initially unsatisfactory specimens. These patients had follow-up to determine whether their thyroid nodules proved to be malignant. RESULTS: Three patients (5.1%) were found to have organ-confined papillary carcinoma of the thyroid, the largest tumor mass measuring 1.2 cm. Six patients (10.2%) had benign adenomas. CONCLUSIONS: In most cases of initially nondiagnostic FNAB of a thyroid nodule, neoplasia is not found subsequently. A minority of cases may still harbor malignancy. None of our patients in whom repeated FNA was either nondiagnostic or suggestive of benign disease were ultimately found to have a malignancy.

Radiation exposure during cardiology fellowship training.

We report catheterization laboratory personnel dose per case during parallel use of two laboratories from different manufacturers. Initially, four working positions were monitored. Review of the data from the first 140 cases showed a wide range of dose per case. Measurements were then limited to diagnostic coronary angiography cases in which a cardiology fellow was the primary operator. On a per case basis, the dose was higher when a fellow was in the laboratory with pulsed progressive fluoroscopy or was in fellowship year one. The increased dose for first year fellows was more related to increased fluoroscopy time than to cine angiography time. This study emphasizes the importance of close supervision of cardiology fellows early in their training to limit dose to patients and personnel, and it underlines the importance of each catheterization laboratory routinely having the actual personnel dose per case measured.

Neuroendocrine stains and proliferative indices of prostatic adenocarcinomas in transurethral resection samples.

OBJECTIVE: To determine whether the quantification of certain neuroendocrine and proliferative markers would help in the prognostic evaluation of prostatic adenocarcinomas obtained during transurethral resection of the prostate (TURP). MATERIALS AND METHODS: Samples from two groups of patients with prostate cancer were examined. One group comprised 23 patients, of whom 12 were stage IV and 11 stage III, all with Gleason scores of > or = 7; this group was designated as high-grade, high-stage (HGHS). The second group comprised 10 consecutive patients with stage T1a adenocarcinoma of the prostate with Gleason scores of < or = 6, designated as low-grade, low-stage (LGLS) tumours. Tumour tissue from each TURP was stained with MIB-1 (an indicator of cell proliferation), neuron-specific enolase (NSE), chromogranin A (ChA) and synaptophysin (Syn), and 1000 cells counted to determine the percentages of positive cells in both benign and malignant tissue. The percentage of MIB-1-positive cells was designated as the proliferative index (PI). Patients were clinically followed to evaluate tumour progression, documented by rising prostate-specific antigen (PSA) levels, X-ray evidence of recurrent or metastatic carcinoma, or tissue biopsy showing malignancy. RESULTS: The mean number of neuroendocrine cells (NEC) for each marker and the mean PI were greater in the HGHS tumours than in the LGLS tumours or surrounding benign tissue of either group (P < 0.01). The LGLS tumours were remarkable for a having mean PI of about twice that of the benign tissue (2.9 and 1.3, respectively, P < 0.01); the NEC in these cases were more frequent in the benign than in the malignant tissue. There was no significant difference between the mean PIs and the mean percentages of NEC in the 14 HGHS tumours that progressed and the nine HGHS tumours that did not (P values 0.37-0.96). CONCLUSIONS: Although the PI assessed by MIB-1 and the number of NEC-positive cells were much higher in HGHS than LGLS tumours, this finding did not appear to have independent prognostic significance. The significance of the higher PI in LGLS tumours than in corresponding benign tissue is uncertain; LGLS tumours had fewer NEC than the surrounding benign tissue. The quantification of any of these four markers (MIB-1, NSE, ChA, Syn) was not prognostically helpful in these groups of cancers present in TURP specimens.

Usefulness of positive troponin-T and negative creatine kinase levels in identifying high-risk patients with unstable angina pectoris.

Troponin-T was measured in patients with chest pain and negative creatine phosphokinase-MB isoenzymes. Patients with elevated troponin-T had a significantly greater risk of cardiac events over the next 6 months than patients with normal troponin-T.