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B D Greenwald

Publications and source records attributed to B D Greenwald.

At least 19 recordsLinked to original sources
PubMed2006

Transcriptional profiling suggests that Barrett's metaplasia is an early intermediate stage in esophageal adenocarcinogenesis.

To investigate the relationship between Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), we determined gene expression profiles of discrete pathological stages of esophageal neoplasia using a sequence-verified human cDNA microarray. Fifty one RNAs, comprising 24 normal esophagi (NE), 18 BEs, and nine EACs were hybridized to cDNA microarrays. Five statistical analyses were used for the data analysis. Genes showing significantly different expression levels among the three sample groups were identified. Genes were grouped into functional categories based on the Gene Ontology Consortium. Surprisingly, the expression pattern of BE was significantly more similar to EAC than to NE, notwithstanding the known histopathologic differences between BE and EAC. The pattern of NE was clearly distinct from that of EAC. Thirty-six genes were the most differentially modulated, according to these microarray data, in BE-associated neoplastic progression. Twelve genes were significantly differentially expressed in cancer-associated BE's plus EAC (as a single combined tissue group) vs noncancer-associated BE's. These genes represent potential biomarkers to diagnose EAC at its early stages. Our results demonstrate that molecular events at the transcriptional level in BE are remarkably similar to BE's-associated adenocarcinoma of the esophagus. This finding alarmingly implies that BE is biologically closer to cancer than to normal esophagus, and that the cancer risk of BE is perhaps higher than we had imagined. These findings suggest that changes modulated at the molecular biologic level supervene earlier than histologic changes, and that BE is an early intermediate stage in the process of EAC.

Adenocarcinoma↗
PubMed2002

Global gene expression profiling in Barrett's esophagus and esophageal cancer: a comparative analysis using cDNA microarrays.

In order to identify and contrast global gene expression profiles defining the premalignant syndrome, Barrett's esophagus, as well as frank esophageal cancer, we utilized cDNA microarray technology in conjunction with bioinformatics tools. We hybridized microarrays, each containing 8000 cDNA clones, to RNAs extracted from 13 esophageal surgical or endoscopic biopsy specimens (seven Barrett's metaplasias and six esophageal carcinomas). Hierarchical cluster analysis was performed on these results and displayed using a color-coded graphic representation (Treeview). The esophageal samples clustered naturally into two principal groups, each possessing unique global gene expression profiles. After retrieving histologic reports for these tissues, we found that one main cluster contained all seven Barrett's samples, while the remaining principal cluster comprised the six esophageal cancers. The cancers also clustered according to histopathological subtype. Thus, squamous cell carcinomas (SCCAs) constituted one group, adenocarcinomas (ADCAs) clustered separately, and one signet-ring carcinoma was in its own cluster, distinct from the ADCA cluster. We conclude that cDNA microarrays and bioinformatics show promise in the classification of esophageal malignant and premalignant diseases, and that these methods can be applied to small biopsy samples.

Barrett Esophagus↗
PubMed2001

Use of antiepileptics in traumatic brain injury: a review for psychiatrists.

In recent years, the number of new antiepileptic agents has been growing, as have the potential applications. Traumatic brain injury (TBI) patients often present with behavioral disturbances that may be amenable to treatment with antiepileptic drugs. These conditions include bipolar disorder, as well as posttraumatic seizures and agitation. We review treatment of these three conditions with newer agents, as well as past literature on treatment with older antiepileptic drugs. We also review the pharmacology of newer antiepileptic drugs and summarize reports that indicate possible utility in the TBI population. Although there is a paucity of evidence for brain injury patients specifically, experience with similar groups suggests that these drugs may be useful. Further trials are indicated to clarify the role of the new antiepileptic agents, which may offer more tolerable side effect profiles than do current treatments.

Anticonvulsants↗
PubMed2001

Gender-related differences in acute rehabilitation lengths of stay, charges, and functional outcomes for a matched sample with spinal cord injury: a multicenter investigation.

OBJECTIVE: To examine the effects of gender on length of stay (LOS), treatment costs, and outcomes by using a matched sample of patients with spinal cord injury (SCI). DESIGN: A 2 x (15 x 3) mixed, block design was used retrospectively to analyze the impact of gender on subjects matched for age, American Spinal Injury Association (ASIA) motor impairment classification, and level of neurologic injury. SETTING: Twenty medical centers in the federally sponsored Spinal Cord Injury Model Systems project. PARTICIPANTS: One thousand seventy-four adult patients with SCI admitted between 1988 and 1998 were assessed at acute-care admission, inpatient rehabilitation admission, and inpatient rehabilitation discharge. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: ASIA motor index and FIM instrument admission, discharge, and efficiency scores; rehabilitation LOS and medical care charges; and discharge disposition. RESULTS: Analysis revealed no gender-related differences in FIM motor scores on admission and discharge. No differences in FIM motor efficiencies or daily change were observed. No significant differences were found for ASIA motor scores on acute-care admission and rehabilitation discharge. No differences in acute rehabilitation LOS and charges were observed. No gender-related differences were seen in the likelihood of discharge to an institutional setting. CONCLUSION: Gender was not a significant factor in functional outcome of SCI patients after acute rehabilitation.

Activities of Daily Living↗
PubMed2001

Factors associated with balance deficits on admission to rehabilitation after traumatic brain injury: a multicenter analysis.

OBJECTIVE: To evaluate how demographics, measures of injury severity, and acute care complications relate to sitting and standing balance in patients with traumatic brain injury (TBI). DESIGN: Multicenter analysis of consecutive admissions to designated TBI Model Systems of Care (TBIMS). SETTING: Ten National Institute for Disability and Rehabilitation Research TBI Model System centers for coordinated acute and rehabilitation care. PARTICIPANTS: 908 adults with TBI were included in the study. MAIN OUTCOME MEASURES: Sitting and standing balance were assessed within 72 hours of admission to inpatient rehabilitation. RESULTS: Age less than 50 years had a significant association with normal sitting and standing balance (P =.001 and.05, respectively). Measures of severity of traumatic brain injury, including admission Glasgow Coma Score, length of posttraumatic amnesia (PTA), length of coma, and acute care length of stay were each significantly related to impaired sitting and standing balance ratings (P <.01). Initial abnormalities in pupillary response had a significant relationship with impairment of sitting (P =.009) but not standing balance. Incidence of respiratory failure, pneumonia, soft tissue infections, and urinary tract infections were all related to impaired sitting balance (P <.01). Presence of intracranial hemorrhages did not have a significant relationship with either sitting or standing balance. Intracranial compression had a significant relationship with standing (P =.05) but not sitting balance. A discriminant function analysis, which included neuroradiological findings, injury severity, and medical complications, could not accurately predict impaired balance ratings. CONCLUSIONS: This study demonstrated that rehabilitation admission balance ratings have a significant relationship with age, multiple measures of severity, and acute care medical complications after TBI. Prospective studies are indicated to evaluate the role balance at rehabilitation admission plays in the functional prognosis of patients with TBI.

Activities of Daily Living↗
PubMed2000

Hypermethylated APC DNA in plasma and prognosis of patients with esophageal adenocarcinoma.

BACKGROUND: The adenomatous polyposis coli (APC) locus on chromosome 5q21-22 shows frequent loss of heterozygosity (LOH) in esophageal carcinomas. However, the prevalence of truncating mutations in the APC gene in esophageal carcinomas is low. Because hypermethylation of promoter regions is known to affect several other tumor suppressor genes, we investigated whether the APC promoter region is hypermethylated in esophageal cancer patients and whether this abnormality could serve as a prognostic plasma biomarker. METHODS: We assayed DNA from tumor tissue and matched plasma from esophageal cancer patients for hypermethylation of the promoter region of the APC gene. We used the maximal chi-square statistic to identify a discriminatory cutoff value for hypermethylated APC DNA levels in plasma and used bootstrap-like simulations to determine the P: value to test for the strength of this association. This cutoff value was used to generate Kaplan-Meier survival curves. All P values were based on two-sided tests. RESULTS: Hypermethylation of the promoter region of the APC gene occurred in abnormal esophageal tissue in 48 (92%) of 52 patients with esophageal adenocarcinoma, in 16 (50%) of 32 patients with esophageal squamous cell carcinoma, and in 17 (39.5%) of 43 patients with Barrett's metaplasia but not in matching normal esophageal tissues. Hypermethylated APC DNA was observed in the plasma of 13 (25%) of 52 adenocarcinoma patients and in two (6.3%) of 32 squamous carcinoma patients. High plasma levels of methylated APC DNA were statistically significantly associated with reduced patient survival (P =.016). CONCLUSION: The APC promoter region was hypermethylated in tumors of the majority of patients with primary esophageal adenocarcinomas. Levels of hypermethylated APC gene DNA in the plasma may be a useful biomarker of biologically aggressive disease in esophageal adenocarcinoma patients and should be evaluated as a potential biomarker in additional tumor types.

Adenocarcinoma↗
PubMed2000

Photodynamic therapy for esophageal cancer. Update.

Although clinical studies with photodynamic therapy have been conducted for over 25 years, only recently has this technique become widely available for the treatment of esophageal cancer. Studies have demonstrated that it is as effective as Nd:YAG therapy for advanced esophageal malignancies while technically being somewhat easier to perform. Preliminary studies in early esophageal cancer also show effectiveness. In many ways, PDT is still in its infancy, and its exact role compared to other endoscopic treatments of esophageal cancer remains to be defined. It is expected that the development of new photosensitizers and light delivery systems will further expand the role of PDT in the diagnosis and management of esophageal neoplasms.

Animals↗
PubMed1999

Opioids for managing patients with chronic pain: community pharmacists' perspectives and concerns.

Previous studies of pharmacists have suggested poor availability of opioids and apprehension about dispensing these drugs. This pilot study surveyed 52 randomly selected New Jersey community pharmacists (response rate = 69%). Reluctance to stock opioids was attributed to concerns about robbery by 14% and to concerns about federal or state investigation by 17%. No correlation was found between respondents who had a high degree of concern about robbery and those who had incurred previous robbery. Of the 20% of respondents who had incurred a prior federal or state investigation, none expressed more than minimal concern about opioid regulatory issues. Pharmacist confidence in the acceptability of opioids for chronic pain was 75% for malignant pain in patients with no history of opioid abuse and declined to 3% for nonmalignant pain in patients with a history of opioid abuse.

Adult↗
PubMed1998

Anti-p53 antibodies in patients with Barrett's esophagus or esophageal carcinoma can predate cancer diagnosis.

BACKGROUND & AIMS: We previously discovered anti-p53 antibodies predating a cancer diagnosis in subjects at increased risk for liver, lung, breast, and prostate cancer. Recently, we reported a significant correlation (P < 0.017) between p53 antibodies and p53 mutations in patients with late-stage esophageal carcinoma. Because others have reported p53 mutations and overexpression of p53 protein in Barrett's esophagus, we studied p53 antibodies in plasma of 88 serially endoscoped patients: 36 with Barrett's metaplasia, 23 with esophageal squamous cell carcinoma, 10 with esophageal adenocarcinoma, and 19 with esophagitis or normal esophagus. METHODS: We used enzyme immunoassay, immunoblotting, and immunoprecipitation assays for p53 antibodies; polymerase chain reaction, denaturant gradient gel electrophoresis, and sequencing for p53 mutations; and immunohistochemistry for p53 protein. RESULTS: p53 antibodies were detected in 4 patients with Barrett's esophagus, including 1 with dysplasia that later progressed to adenocarcinoma, and in 10 cancer patients (P = 0.002) (8 squamous and 2 adenocarcinoma), 2 of whom (1 squamous, 1 adenocarcinoma) had antibodies before cancer was diagnosed. Other patient groups were too small for informative statistical analysis. Six antibody-positive cancer patients had p53 mutations, whereas 2 patients with cancer and 1 with Barrett's esophagus with antibodies had p53 protein overexpressed in esophageal tissues. CONCLUSIONS: Patients with Barrett's esophagus and esophageal cancer can develop p53 antibodies that may predate the clinical diagnosis of malignancy.

Adenocarcinoma↗
PubMed1998

Esophagopericardial fistula arising from Barrett's esophagus.

Esophagopericardial fistula is a rare complication of numerous benign, malignant, and traumatic conditions of the esophagus. Approximately 100 cases of fistulae between the esophagus and heart have been reported. We describe the second reported case of an esophagopericardial fistula secondary to a benign esophageal ulcer within Barrett's mucosa without prior surgery. The radiologic, endoscopic, and surgical management of this case are discussed.

Adult↗
PubMed1997

FHIT gene alterations in esophageal cancer and ulcerative colitis (UC).

FHIT (fragile histidine triad gene), a candidate tumor suppressor gene, was recently identified and cloned at chromosome 3p14.2. Alterations of this gene have been reported in a number of primary human tumors, including colorectal, esophageal, gastric and lung carcinomas. However, some reports have found no abnormalities in this gene. We investigated a total of 63 primary esophageal tumors, nine esophageal cancer cell lines and 17 ulcerative colitis-associated neoplasms (UCANs) for alterations of FHIT. In 13 esophageal tumors, we employed overlapping reverse transcriptase-PCRs (RT-PCRs) to amplify and sequence the complete open reading frame of FHIT. One of 13 primary esophageal tumors analysed by RT-PCR expressed no detectable FHIT transcript; the remaining 12 expressed normal-sized transcripts with wild-type open reading frame sequences. In an additional 50 esophageal tumors, the polymorphic microsatellite loci D3S1300 and D3S1313 were used to evaluate loss of heterozygosity (LOH) at 3p14.2. Eleven of these 50 tumors showed LOH at one or both loci. In all these 11 tumors, genomic PCR and direct sequencing of FHIT exons 5-9 was performed. This analysis revealed that none of these 11 primary esophageal tumors contained any alterations in the FHIT open reading frame or adjacent intron sequences. Finally, among 17 UCANs, the in vitro synthesized protein (IVSP) assay detected no truncated protein products, nor were there any abnormalities in size or DNA sequence of FHIT RT-PCR products. However, in six of nine esophageal carcinoma cell lines, no FHIT RT-PCR product was detectable using either of the overlapping primer sets. Genomic PCR and direct sequencing of exons 5-9, also performed in these nine cell lines, revealed wild-type sequence in eight cell lines; however, one cell line contained no exon 5 PCR product. This cell line also lacked detectable FHIT transcript. These data suggest that the open reading frame of FHIT is not important in the development or progression of most primary esophageal carcinomas or UCANs, although lack of expression of the FHIT transcript may be common in esophageal cancer-derived cell lines. The possibility of an additional tumor suppressor gene at chromosome 3p14.2 remains to be evaluated.

Acid Anhydride Hydrolases↗
PubMed1997

A transforming growth factor beta 1 receptor type II mutation in ulcerative colitis-associated neoplasms.

BACKGROUND & AIMS: Numerous gastrointestinal tumors, notably sporadic and ulcerative colitis (UC)-associated colorectal carcinomas and dysplasias, gastric cancers, and esophageal carcinomas, manifest microsatellite instability. Recently, a transforming growth factor beta 1 type II receptor (TGF-beta 1RII) mutation in a coding microsatellite was described in colorectal carcinomas showing instability. One hundred thirty-eight human neoplasms (61 UC-associated, 35 gastric, 26 esophageal, and 16 sporadic colorectal) were evaluated for this TGF-beta 1RII mutation. METHODS: Whether instability was present at other chromosomal loci in these lesions was determined. In lesions manifesting or lacking instability, the TGF-beta 1RII coding region polydeoxyadenine (poly A) microsatellite tract was polymerase chain reaction amplified with 32P-labeled deoxycytidine triphosphate. Polymerase chain reaction products were electrophoresed on denaturing gels and exposed to radiographic film. RESULTS: Three of 18 UC specimens with instability at other chromosomal loci (17%) showed TGF-beta 1RII poly A tract mutation, including 2 cancers and 1 dysplasia; moreover, 2% of UC specimens without instability (1 of 43) (1 cancer), 81% of unstable sporadic colorectal cancers (13 of 16), and none of the 61 stable or unstable gastric or esophageal cancers contained TGF-beta 1RII mutations. CONCLUSIONS: Mutational inactivation of the poly A microsatellite tract within TGF-beta 1RII occurs early and in a subset of unstable UC neoplasms and commonly in sporadic colorectal cancers but may be rare in unstable gastric and esophageal tumors.

Activin Receptors, Type I↗
PubMed1996

Alterations of transforming growth factor-beta 1 receptor type II occur in ulcerative colitis-associated carcinomas, sporadic colorectal neoplasms, and esophageal carcinomas, but not in gastric neoplasms.

BACKGROUND & AIMS: Gastric cancers, sporadic colorectal cancers, and ulcerative colitis (UC)-associated colorectal carcinomas and dysplasias manifest microsatellite instability (MI); however, esophageal carcinomas rarely exhibit MI. Recently, a transforming growth factor-beta 1 type II receptor (TGF-beta 1RII) mutation in a coding microsatellite was described in primary colorectal carcinomas demonstrating MI. No previous studies of TGF-beta 1RII have addressed mechanisms of inactivation other than MI in human tumors; furthermore, MI-negative tumors have not been examined for TGF-beta 1RII mutation. We evaluated 138 primary human neoplasms for mutation in the poly-A microsatellite tract of TGF-beta 1RII. Additionally, a group of esophageal tumors was evaluated for the expression of TGF-beta 1RII messenger RNA (mRNA). METHODS: First, we determined whether MI was present at other chromosomal loci in these lesions. The poly-deoxyadenine (poly-A) microsatellite tract within the TGF-beta 1RII coding region was then PCR-amplified. In a group of MI-negative esophageal tumors, RT-PCR was performed to determine the expression of TGF-beta 1RII mRNA. RESULTS: Among 17 MI+ UC specimens, 3 (18%) demonstrated TGF-beta 1RII poly-A tract mutation (2 cancers and 1 dysplasia), while 2 (4%) of 44 MI-negative UC specimens (1 dysplasia and 1 tumor), and 13 (81%) of 16 MI+ sporadic colorectal cancers, contained TGF-beta 1RII poly-A mutation. No gastric or esophageal tumors contained TGF-beta 1RII mutation. Among 21 MI-negative esophageal carcinomas. 6 cases (28.5%) had TGF-beta 1RII transcripts that were low or undetectable by RT-PCR. CONCLUSIONS: Mutation within the poly-A microsatellite tract of TGF-beta 1RII occurs early in a subset of UC-neoplasms and commonly in sporadic colorectal cancers, but may be rare in MI+ gastric tumors. Diminished expression of TGF-beta 1RII mRNA in esophageal tumors suggests that mechanisms of inactivation in this gene other than MI play a role in esophageal carcinogenesis.

Colitis, Ulcerative↗
PubMed1994

p53 protein expression in ulcerative colitis-associated colorectal dysplasia and carcinoma.

The frequency and timing of p53 inactivation in ulcerative colitis (UC)-associated tumorigenesis were investigated using immunohistochemistry (IHC) to detect p53 protein overexpression in 56 carcinomas and 40 dysplastic epithelia derived from 58 patients with UC undergoing colectomy for neoplasia. p53 DNA in 25 of the carcinomas also was evaluated by single-strand conformation polymorphism analysis (SSCP) to detect point mutations in exons 5-8 and by loss of heterozygosity analysis to detect allelic deletions. Point mutations were detected in 20 of the 25 carcinomas (80.0%) undergoing both IHC and DNA analysis. One carcinoma contained an allelic deletion but no mutations of the corresponding allele within the region tested. p53 overexpression occurred in 16 (76.2%) of the 21 carcinomas with point mutations and/or allelic deletions but not in any of those with wild type DNA. Of the 56 carcinomas evaluated by IHC, p53 overexpression occurred in 34 carcinomas (60.7%). The proportion of positive tumors was independent of stage, anatomic location, differentiation, and histological subtype. Overexpression was observed in nine of 20 dysplastic masses devoid of and situated remote from carcinoma (45.0%) and correlated positively with increasing grade of dysplasia (P < .025). In contrast, overexpression occurred in 16 of 20 dysplastic epithelia situated adjacent to carcinoma (80.0%) and correlated with overexpression by the corresponding carcinomas but not with the grade of dysplasia present (P = .013). It is concluded that p53 overexpression can be detected by IHC in most, although not all, UC-associated carcinomas with p53 mutations and/or allelic deletions. Based on this method, p53 overexpression occurs frequently in UC-associated carcinomas regardless of stage and pathological characteristics, in noncancerous dysplastic masses with high grade dysplasia, and in dysplasias of all grades situated adjacent to carcinomas. These findings implicate p53 inactivation in the progression from dysplasia to carcinoma in UC and suggest that its occurrence in dysplastic epithelium may be an independent marker of malignant potential.

Carcinoma↗
PubMed1993

p53 point mutations in dysplastic and cancerous ulcerative colitis lesions.

BACKGROUND: The molecular basis of colorectal dysplasia and carcinoma arising in ulcerative colitis is poorly understood. Loss of heterozygosity involving the tumor suppressor gene p53 occurs frequently in neoplastic ulcerative colitis lesions. Point mutation affecting p53 is associated with loss of heterozygosity in other cancers. Therefore, it was determined whether p53 point mutation occurs in ulcerative colitis-associated neoplasia. METHODS: Single-strand conformation polymorphism analysis, DNA sequencing, and loss of heterozygosity studies were performed on 45 patients with ulcerative colitis-associated dysplasia and carcinoma. RESULTS: Point mutations were detected in 26 lesions from 20 patients, including 18 carcinomas, 6 dysplasia-associated masses, 1 flat dysplasia, and 1 lymph node metastasis. In two cases, identical p53 mutations were observed in both carcinoma and adjacent dysplasia. Missense mutations causing amino acid substitutions as well as nonsense mutations resulting in premature stop codons were seen. Tandem mutations, in which more than 1 sequence alteration occurred on the same allele of p53, were also detected. Point mutation was accompanied by loss of the other p53 allele in 8 of 10 patients informative for both loss of heterozygosity and mutation assays. CONCLUSIONS: These findings suggest that inactivation of p53 by mutation and loss of heterozygosity is a common mechanism of malignant transformation in ulcerative colitis. They also imply that in contrast to sporadic colorectal carcinoma, ulcerative colitis-associated neoplastic progression may involve p53 inactivation at relatively early, noninvasive stages.

Chromosome Deletion↗
PubMed1992

Loss of heterozygosity affecting the p53, Rb, and mcc/apc tumor suppressor gene loci in dysplastic and cancerous ulcerative colitis.

Allelic deletions of tumor suppressor genes have been observed frequently in a variety of human tumors. These losses are believed to contribute to the development of human cancer. Three of the most frequently deleted chromosomal loci contain the tumor suppressor genes p53, retinoblastoma (Rb), and mcc/apc. In order to detect loss of heterozygosity (LOH) within these genes in dysplastic and cancerous ulcerative colitis, we used an application of the polymerase chain reaction. LOH affecting p53 was observed in 8 of 17 (47%) of heterozygous patients, while LOH of Rb and the mcc/apc locus was observed in 9 of 27 (33%) and 13 of 39 (33%) of heterozygotes, respectively. Among 35 patients heterozygous at 2 or more loci, LOH of p53, Rb, and/or mcc/apc was observed in 18 (51%). LOH was more common in left-sided neoplasms. These data suggest that allelic deletion of p53, Rb, mcc, and/or apc is involved in the pathogenesis and/or progression of at least a subset of colonic dysplasias and carcinomas occurring in the setting of ulcerative colitis.

Adenocarcinoma↗
PubMed1992

Candidal endophthalmitis after lithotripsy of renal calculi.

Candidal endophthalmitis is most commonly due to hematogenous seeding of the eye by Candida albicans. Although it is most often seen as a manifestation of disseminated candidiasis in patients who are seriously ill, other patients may have candidal endophthalmitis as the only evidence of fungal infection. We have presented a case of endophthalmitis due to C albicans in a patient who had bilateral renal calculi and who had received multiple antibiotics and extracorporeal shock wave lithotripsy.

Candidiasis↗