PubMed Health⌕ Search

Biomedical subjects

K Lewin

Publications and source records attributed to K Lewin.

At least 19 recordsLinked to original sources
PubMed2001

Effective and safe endoscopic reversal of nondysplastic Barrett's esophagus with thermal electrocoagulation combined with high-dose acid inhibition: a multicenter study.

BACKGROUND: Barrett's esophagus is a metaplastic change in the esophageal lining with an increased risk for adenocarcinoma. Multiple endoscopic techniques have been applied in an effort to reverse Barrett's. This is a multicenter trial defining the efficacy and safety of multipolar electrocoagulation combined with high-dose acid inhibition. METHODS: Patients with a 2- to 6-cm segment of Barrett's esophagus without dysplasia were enrolled at 3 centers. They were treated with omeprazole 40 mg twice daily and then with up to 6 sessions with electrocoagulation aimed at eliminating all the endoscopically apparent Barrett's. Four quadrant large-capacity biopsies every 2 cm were centrally assessed for residual intestinal metaplasia. RESULTS: Fifty-eight patients reached the endpoint of failure of visual reversal of Barrett's after 6 treatment sessions or a 6-month follow-up after the last session. Eighty-five percent had visual reversal and 78% both visual and histologic reversal. Four patients had histologic evidence of residual intestinal metaplasia. Transient esophageal symptoms were common. One patient developed a stricture requiring dilation and one required overnight hospitalization for chest pain. CONCLUSIONS: The majority of patients with 2 to 6 cm of nondysplastic Barrett's esophagus can be safely reversed with this combination therapy. Long-term follow-up will be necessary to document the durability of the new squamous epithelium.

Adult↗
PubMed2000

Effects of supplemental alpha-tocopherol and beta-carotene on colorectal cancer: results from a controlled trial (Finland)

BACKGROUND: Some epidemiological investigations suggest that higher intake or biochemical status of vitamin E and beta-carotene might be associated with reduced risk of colorectal cancer. METHODS: We tested the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of colorectal cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a double-blind, placebo-controlled trial among 29,133 50-69-year-old male cigarette smokers. Participants were randomly assigned to receive alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or a placebo daily for 5-8 years. Incident colorectal cancers (n = 135) were identified through the nationwide cancer registry, and 99% were histologically confirmed. Intervention effects were evaluated using survival analysis and proportional hazards models. RESULTS: Colorectal cancer incidence was somewhat lower in the alpha-tocopherol arm compared to the no alpha-tocopherol arm, but this finding was not statistically significant (relative risk (RR) = 0.78, 95% confidence interval (CI) 0.55-1.09; log-rank test p = 0.15). Beta-carotene had no effect on colorectal cancer incidence (RR = 1.05, 95% CI 0.75-1.47; log-rank test p = 0.78). There was no interaction between the two substances. CONCLUSION: Our study found no evidence of a beneficial or harmful effect for beta-carotene in colorectal cancer in older male smokers, but does provide suggestive evidence that vitamin E supplementation may have had a modest preventive effect. The latter finding is in accord with previous research linking higher vitamin E status to reduced colorectal cancer risk.

Aged↗
PubMed2000

Gastric dysplasia: the Padova international classification.

A worldwide-accepted histologic, classification of the gastric carcinomatous and precancerous lesions is a prerequisite for a consistent recording of epidemiologic data and for both developing and evaluating primary and secondary preventive efforts. Different nomenclatures have been proposed for gastric precancerous lesions in eastern countries and in Japan. This article presents a classification of gastric precancerous lesions resulting from an international consensus conference involving pathologists of different countries. Five main diagnostic categories are identified. To allow comparisons with the nomenclature proposed by the Japanese Research Society for Gastric Cancer, each category was also assigned a numeric identification: 1 = normal, 2 = indefinite for dysplasia, 3 = noninvasive neoplasia, 4 = suspicious for invasive cancer, and 5 = cancer. The interobserver reproducibility of the histologic classification was tested in a series of 46 cases. By collapsing benign alterations (categories 1+2) versus noninvasive neoplasia (category 3) versus suspicious for invasive cancer and fully appearing carcinomatous lesions (categories 4+5), the general agreement value was 77.7%, whereas kappa coefficient was 0.63. By examining gastric precancerous lesions from diverse populations, the authors agreed that the gastric precancerous process is universal and the differences in nomenclatures are merely semantics. The international Padova classification of the gastric precancerous lesions is submitted to the attention of the international scientific community, which is invited to test and to improve on it.

Adenocarcinoma↗
PubMed2000

The economic impact of the diagnosis of dysplasia in Barrett's esophagus.

OBJECTIVE: Cost-effective strategies for identifying patients with Barrett's esophagus who are most likely to develop cancer have not been developed. Surveillance endoscopy is currently used, and we hypothesized that more frequent surveillance intervals would identify patients with "transient positive" diagnoses of dysplasia--dysplasia found on one examination but not on subsequent ones. Our aim was to explore the potential economic impact of transient positive diagnoses of dysplasia on alternative surveillance strategies over a 10-yr period. METHODS: Data were derived from a 2-yr randomized, prospective study comparing omeprazole to ranitidine in 95 patients with Barrett's esophagus. A transient positive diagnosis of dysplasia was defined as a patient who was diagnosed with dysplasia during the study period but whose 24-month biopsies revealed no dysplasia. We calculated the number of transient positive diagnoses of dysplasia and modeled the potential economic impact of a diagnosis of dysplasia over a 10-yr period. RESULTS: Thirty patients (31%) had at least one reading of dysplasia during the study period. Nineteen patients (20%) had a transient positive diagnosis of dysplasia. During the study period, no cancers were found. A surveillance strategy of every other year and every 6 months for dysplasia would result in 1072 endoscopies over a 10-yr period at a discounted cost of $1,587,184. A total of 61% of endoscopies would be because of transient positive diagnoses of dysplasia. A strategy of yearly surveillance and every 6 months for dysplasia would result in 1404 endoscopies at a discounted cost of $2,096,733, of which 28% would result from transient positive diagnoses of dysplasia. The discounted incremental costs of more frequent surveillance in this cohort of patients over 10 yr is $509,549. CONCLUSIONS: Based on current practice strategies, transient positive diagnoses of dysplasia account for 28-61% of endoscopies in Barrett's surveillance programs. This analysis suggests that the endoscopy workload and costs associated with surveillance could be substantially reduced if patients with transient positive diagnoses of dysplasia reverted to usual surveillance after two negative examinations.

Anti-Ulcer Agents↗
PubMed1999

Xenotransplantation of fetal porcine hepatocytes in rats using a tissue engineering approach.

Hepatocytes can be successfully transplanted into highly vascular sites such as the spleen, liver, and lungs. Subcutaneous sites lack adequate vascularization to nutritionally support transplanted hepatocytes. We recently reported that matrix-immobilized angiogenic growth factors, e.g., endothelial cell growth factor (ECGF), can induce a high degree of neovascularization. Using this technique, we explored the possibility of transplanting isolated fetal porcine hepatocytes to create liver tissue organoids at a specific subcutaneous site. We evaluated chitosan as a scaffold biomaterial because of its structural similarity to glycosaminoglycans; glycosaminoglycans play a critical role in cell attachment, differentiation, and morphogenesis. Freshly isolated fetal porcine hepatocytes (FPH) (viability greater than 97%) were cultured on modified chitosan scaffolds and transplanted into rat groin fat pads with or without ECGF-induced neovascularization. Cell density and attachment kinetics on chitosan were examined by scanning electron microscopy (SEM) and quantified using a flavianic acid binding assay. Hepatocyte viability and liver organoid formation were examined immunohistochemically. FPH transplanted without prior neovascularization died within 1 day post-transplantation. When transplanted after ECGF-induced neovascularization, FPH thrived for at least 2 weeks and formed liver tissue like structures. Immunohistochemical analysis revealed the presence of hepatocyte-specific cytokeratin staining as well as the presence of alpha-fetoprotein. Light microscopy and SEM revealed that FPH did not change their morphology after attachment to the chitosan surfaces. Thus, chitosan-based biomaterial surfaces have good hepatocyte attachment properties. However, extensive neovascularization is essential for hepatocyte survival and organoid formation. In the future, chitosan-based biomaterials may be useful as scaffolds for creating liver tissue organoids.

Animals↗
PubMed1999

Clinical and pathologic overlap in nonsteroidal anti-inflammatory drug-related small bowel diaphragm disease and the neuromuscular and vascular hamartoma of the small bowel.

Diaphragm disease (DD) is a radiographically subtle cause of small bowel obstruction and is part of the spectrum of diseases associated with nonsteroidal anti-inflammatory drug injury. The neuromuscular and vascular hamartoma (NMVH) is a nonepithelial hamartomatous, submucosally based proliferation of mature submucosal elements capable of causing small bowel obstruction. The authors report two patients in whom the clinical setting and gross pathology are that of DD, but the histologic characterization is identical to that described for NMVH. It is probable that in some patients the two diseases overlap so that some patients readily fit the criteria for both entities.

Aged↗
PubMed1993

Cryopreserved microencapsulated hepatocytes--transplantation studies in Gunn rats.

Hepatocyte transplantation has been shown to provide significant metabolic support in several animal models of liver diseases. However, for it to be a viable alternative for supplementation of liver function in disease, large quantities of isolated hepatocytes would be necessary. At the present time there are no inexpensive routine methods for cryopreservation of hepatocytes. Existing procedures are cumbersome and require expensive programmable freezers. Hepatocyte cultures are sensitive and easily damaged in handling. By utilizing techniques of microencapsulation and cryopreservation we have attempted to overcome these problems. We have developed a simple, convenient, and inexpensive technique for the long-term storage of hepatocytes. Biological activity of the nonfrozen isolated encapsulated hepatocytes (IEH) and cryopreserved IEH (cIEH) was assessed both in tissue culture and by transplantation in Gunn rats. Significant urea and protein syntheses were detectable during the 10-day culture period even in the 30-day cIEH. Additionally, transplanted IEH and cIEH significantly reduced hyperbilirubinemia in Gunn rats for up to 30 days posttransplantation. Control (empty) microcapsules did not lower serum bilirubin levels. Thus we conclude: (1) cryopreservation of IEH is a convenient and cost-effective method for preserving and storing hepatocytes; (2) cryopreserved IEH function as well as nonfrozen IEH both in vitro and in vivo; (3) microencapsulation may protect hepatocytes from the adverse effects of cryopreservation.

Animals↗
PubMed1992

Steroid receptors in surgical pathology. With special reference to small mammographically detected breast lesions.

The cellular receptors for estrogen, progesterone, and other steroid hormones appear in the cytosol fraction of homogenated specimens of hormonal target tissues. These receptors have traditionally been detected and quantitated by biochemical techniques that involve binding tritium-labelled marker steroids to the receptor proteins. An important recent development has been the creation of various monoclonal antibody reagents that specifically recognize antigenic determinants on receptor molecules.

Biopsy↗
PubMed1991

Intraobserver and interobserver variation in the histopathological assessment of liver allograft rejection. The Liver Transplantation Database (LTD) Investigators.

A study to determine the reproducibility of histopathological findings and diagnoses of rejection was carried out on a series of 42 liver allograft needle biopsy specimens by five pathologists practicing at four liver transplant centers. Pathologists from each of the four centers read each slide independently on two different occasions and were asked to assess 12 histopathological features and render a diagnosis. For all histological variables, the intrarater agreement was higher than the interrater agreement. Moderate to excellent agreement occurred among the pathologists about all histological variables thought to be important in establishing the diagnosis of acute rejection (i.e., portal tract inflammation, subendothelial inflammation and bile duct damage). Other variables such as lobular disarray, bile duct proliferation and particularly arteritis, however, were only fairly or poorly reproducible. Surprisingly, the diagnosis of acute rejection was more reproducible than the individual histopathological findings that were thought to be the basis for the diagnosis. The agreement for the diagnosis of chronic rejection, however, varied according to observer. We noted that relatively inexperienced observers within this group had some difficulties agreeing with more experienced observers in establishing a diagnosis of chronic rejection. These findings demonstrate that the histopathological diagnosis of acute cellular liver allograft rejection is highly reproducible within a group of experienced pathologists and that this diagnosis can be pooled in a common data base with confidence.

Biopsy, Needle↗
PubMed1990

Restoration of liver function in Gunn rats without immunosuppression using transplanted microencapsulated hepatocytes.

Microencapsulation of cells within synthetic semipermeable membranes is a novel technique that enables the transplantation of cell cultures without the need for immunosuppression. We have previously shown that transplanted isolated encapsulated hepatocytes can provide sufficient short-term metabolic support to improve the survival of animals with galactosamine-induced fulminant hepatic failure. Here we have demonstrated the feasibility of isolated encapsulated hepatocyte transplantation in providing long-term metabolic liver support in Gunn rats. Gunn rats have a congenital inability to conjugate bilirubin and thus exhibit lifelong hyperbilirubinemia. We studied the feasibility of isolated encapsulated hepatocyte transplantation in restoring this specific liver function. Free hepatocytes, isolated from male Wistar rats, were microencapsulated with collagen within a trilayered sodium alginate-poly-L-lysine-sodium alginate membrane using techniques developed in our laboratory. A total of 45 Gunn rats underwent intraperitoneal transplantation with free hepatocytes (5 x 10(7], isolated encapsulated hepatocytes (5 x 10(7], control (empty) microcapsules or no transplant (untreated controls). Serum bilirubin levels were monitored daily for 10 days after transplantation, and subsequent weekly samples were obtained for up to 1 mo. Microcapsules were studied by light and electron microscopy 1 mo after transplantation. During the first week after transplantation, the mean maximum reduction in serum bilirubin levels for the isolated encapsulated hepatocytes, free hepatocytes and control microcapsule transplanted groups was 45.7%, 18.6% and 14.3%, respectively. For up to 1 mo thereafter the mean reduction in serum bilirubin levels in these respective groups was 34.8%, 13.5% and 3.3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1989

Amanita poisoning: treatment and the role of liver transplantation.

Fatal mushroom poisoning has long been recognized as a major health problem in western Europe and more recently in the United States. The majority of deaths are attributable to the genus Amanita. Amanita phalloides (death cap) has been found with increasing frequency across the United States and presents a significant health hazard in this country to those who pick and consume wild mushrooms. This article discusses the pharmacologic basis and clinical manifestations of Amanita intoxication. It outlines the rationale of various treatment modalities and, from these, summarizes a protocol that the authors believe will be useful to the clinician. In addition, two patients are presented who underwent successful orthotopic liver transplantation for fulminant hepatic failure secondary to Amanita poisoning. The role of liver transplantation both acutely and as treatment for chronic active hepatitis secondary to severe intoxication is discussed.

Adult↗
PubMed1989

Malignant islet cell tumor with rhabdomyosarcomatous differentiation.

We present a widely metastatic islet cell tumor of the pancreas with focal areas resembling rhabdomyosarcoma. To our knowledge, this is the first reported case of islet cell/carcinoid tumor exhibiting such differentiation. Desmin was localized to the rhabdoid areas by immunohistochemistry. Cross striations were not seen by light microscopy, but Z-lines and thick filaments were seen on electron microscopy.

Adenoma, Islet Cell↗
PubMed1989

Randomized prospective trial of OKT3 for early prophylaxis of rejection after liver transplantation.

A group of 52 liver transplant patients was prospectively randomized to receive prophylactic immunosuppressive therapy consisting of either Orthoclone OKT3 for 14 days, azathioprine, and steroids (25 patients); or cyclosporine, azathioprine, and steroids (27 patients). The groups were similarly matched for age, diagnosis, and Child's classification. The patients were studied to determine the effect of these two regimens on the incidence of rejection, infection, renal dysfunction, and mortality. Seven rejection episodes, as determined by clinical and histological criteria, occurred in seven of 25 patients (28%) receiving OKT3 compared with 18 episodes in 27 patients (67%) receiving cyclosporine during the first 14 days after transplantation (P less than 0.02). In 20% of the OKT3 patients, CD3+ levels of greater than 10% developed during therapy, and 16% of the patients developed anti-OKT3 antibodies during OKT3 treatment. Five patients were retreated with OKT3 for steroid-resistant acute rejection episodes; all had resolution of the rejection episode. Infectious complications were similar in each group. Renal function, as measured by serum creatinine, was significantly better with OKT3 than with cyclosporine (P less than 0.003) at 14 days. We conclude that prophylactic OKT3 is effective in reducing the number of early rejection episodes after liver transplantation; after 14 days the incidence of rejection is similar; reuse of OKT3 has been successful in liver transplant patients; infectious complications are similar between OKT3 and cyclosporine; and OKT3 preserves renal function better than cyclosporine and is thus indicated in patients with compromised preoperative renal function.

Antibodies, Anti-Idiotypic↗
PubMed1988

Observer variation in the diagnosis of dysplasia in Barrett's esophagus.

The potential value of biopsy surveillance of patients with Barrett's esophagus for dysplasia is diminished by a lack of agreement on the diagnostic criteria for dysplasia. In a preliminary consensus conference, experienced gastrointestinal pathologists from four medical centers agreed on criteria for a five-tiered histologic classification of dysplasia in Barrett's esophagus--negative for dysplasia, indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia, and intramucosal carcinoma. Eight morphologists in the four centers tested the criteria for interobserver agreement by examining a set of coded slides that had been chosen to include some especially difficult interpretative problems in all five histologic classifications. Interobserver agreement of 85 and 87% was achieved in successive reviews when the combined group of high-grade dysplasia and intramucosal carcinoma was compared with the combined group of low-grade dysplasia, indefinite for dysplasia, and negative for dysplasia. Comparison of other groups yielded less agreement. For example, negative for dysplasia could be distinguished from all other diagnoses with an interobserver agreement of 72%. We conclude that experienced gastrointestinal morphologists can diagnose high-grade dysplasia and intramucosal carcinoma with a high degree of agreement and thus can detect those patients who may need immediate rebiopsy or esophageal resection. Either further refinement of histologic criteria or alternate diagnostic methods will be needed to achieve the reproducible diagnosis of indefinite changes and low-grade dysplasia. This is important because patients with such changes theoretically merit closer endoscopic surveillance.

Barrett Esophagus↗
PubMed1987

AIDS: an overview of the pathology.

This article reviews the findings at postmortem examination on AIDS and separately details the surgical pathology of the gastrointestinal tract, liver, lymph nodes, and skin in these patients. Emphasis is placed upon the light microscopic features of the specimens commonly received in surgical pathology so as the promote the ready diagnosis of this important and grave disorder.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Carcinoid tumors and the mixed (composite) glandular-endocrine cell carcinomas.

Carcinoid tumors display a wider histologic spectrum than was previously thought. Some tumors may show atypical features such as glandular profiles, a spindle cell pattern, squamous or osteoid metaplasia, or pleomorphism. In rare cases they may be poorly differentiated and resemble undifferentiated carcinoma or lymphoma. As is well known, some carcinoids are associated with well-defined syndromes, such as the carcinoid or the Zollinger-Ellison syndrome, due to the secretion of amines or peptides. Immunohistochemical analysis of these tumors, however, has shown that whereas one amine or peptide may predominate, most are multihormonal. These findings are also seen with the clinically silent tumors such as the foregut and hindgut carcinoids. Furthermore, the immunohistochemically demonstrated amines and peptides in the primary tumor do not necessarily correspond to those normally found in the overlying endocrine cells. An increasing number of tumors have recently been described which contain an admixture of neoplastic endocrine and nonendocrine epithelial cells. Thus, the classification of gut mucosal tumors into carcinomas and endocrine tumors has had to be modified to include those tumors which have been designated as mixed or composite tumors. These have been further subdivided into several distinctive histologic types. Some of these tumors, such as the microglandular-goblet cell carcinomas, have a distinctive clinical behavior, whereas others, such as the adenoendocrine cell carcinomas, appear to behave in a manner similar to adenocarcinoma. Additionally, there is another tumor type, namely the amphicrine tumor, which differs from the mixed tumors in that endocrine and epithelial cell constituents are present within the same cell.

Aged↗