[Dr. Anna Wildikaan].
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Biomedical subjects
Publications and source records attributed to S Eidelman.
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BACKGROUND: Anorectal malignant melanoma is a rare tumor with an extremely poor prognosis. DNA flow cytometric study as well as detailed immunohistochemical study have not been reported previously. METHODS: Eighteen cases of anorectal melanoma were studied, including immunohistology for melanoma markers and epithelial markers and DNA flow cytometric study of paraffin blocks. RESULTS: Most patients were Ashkenazi Jews, compared with Sephardi Jews and Arabs. Of the 17 patients followed, 14 died of disease at 4-39 months from presentation. Three patients were alive with disease at 12, 53, and 72 months of follow-up. Tumor thickness ranged from 3-35 mm (mean, 12.8 mm). The 2 long term survivors had tumor thickness < or = 7 mm. No correlation was found between the mode of primary surgical treatment (8 patients: abdominoperineal resection; 10 patients: local excision) and outcome. Vimentin, HMB-45, and S-100 protein stainings were positive in 18, 17, and 15 tumors, respectively. Polyclonal carcinoembryonic antigen (CEA), broad-spectrum cytokeratin, epithelial membrane antigen, monoclonal CEA, and TAG-72 (B72.3) stainings were positive in 13, 3 (only focal and rare staining), 2, 0, and 0 tumors, respectively. Thirteen tumors had adequate material for DNA analysis, and all were DNA aneuploid. S-phase fraction could be assessed in 11 tumors and ranged from 7.7-24% (mean, 14%). An S-phase fraction of < 10% was observed in the 2 long term survivors. CONCLUSIONS: Anorectal melanoma in this study carried a grave prognosis. The frequent staining for polyclonal CEA (with negative monoclonal CEA staining) was probably due to nonspecific cross-reacting antigens. The occasional staining for epithelial markers warrants a comprehensive immunohistochemical study to ensure a correct diagnosis, especially in small biopsies of amelanotic undifferentiated tumors that lack junctional changes. The aneuploidy of all tested tumors reflected their highly malignant behavior. A trend toward longer survival was observed in patients with thin tumors and an S-phase fraction of < 10%. However, due to the small number of survivors, the latter observation should be further tested in a larger scale series.
Treatment of perianal inflammatory lesions in Crohn's disease (CD) is unsatisfactory and novel treatment modalities are pursued. We have recently reported a good clinical effect of hyperbaric oxygen (HBO) treatment in perianal CD. In the present study, seven patients with perianal CD were subjected to daily sessions of HBO in a multiplace hyperbaric chamber. Each patient received a total of 20 sessions during a time period of 1 month, and IL-1, IL-6, and TNF-alpha measurements were done several times during the initial sessions and after completing therapy. Pretreatment cytokine levels were elevated in patients compared to age-matched 10 normal controls. During the first 7 days of treatment, IL-1, IL-6, and TNF-alpha levels in supernatants of LPS-stimulated monocytes derived from patients' peripheral blood were decreased compared to pretreatment levels. Parallel measurements of serum IL-1 levels revealed an initial elevation and thereafter decreased levels, which remained low throughout the first week of HBO treatment. After completion of therapy, cytokine levels increased to pretreatment values. We conclude that alterations in secretion of IL-1, IL-6, and TNF-alpha may be related to the good clinical effect of HBO treatment in CD patients with perianal disease.
Familial adenomatous polyposis (FAP), an autosomal dominant inherited disease, confers a high risk of colon cancer. For presymptomatic diagnosis of FAP, we performed linkage studies in three unrelated Israeli families with FAP, using seven polymorphic systems around or at the APC locus on chromosome 5q. These systems are constituted of three DNA probes, recognizing four restriction fragment length polymorphism: C11p11, YN5.48 and pi227; three cytosine-adenine repeat markers: D5S318, D5S346 and MBC; and one intragenic polymorphism: APC-SspI. A meiotic recombination event was detected, apparently between the FAP gene and probe pi227. Based on the different analysis systems, we determined the haplotype at the APC locus in 11 at-risk individuals of the three families, six of whom were found to carry the disease-linked allele. Additionally, we identified a new FAP patient, in whom sigmoidoscopy showed the presence of adenomatous polyps throughout the colon.
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We performed a controlled study to evaluate the role of cefonicid in preventing infectious complications related to retrograde cholangiopancreatography (ERCP). Consecutive patients were randomized to receive prophylaxis with cefonicid (1 g intravenously) 1 hour before the procedure or to be untreated controls. During a 26-month period, 179 ERCPs, including 93 therapeutic procedures, were performed on 164 patients. Prophylaxis was administered before 88 procedures (49%). The rate of bacteremia among treated patients was similar to that among controls (3% vs. 2%, respectively; P = .4). The rate of cholangitis was also similar among both groups (8% vs. 2%, respectively; P = .07). There were no episodes of sepsis, and none of the patients died. The rate of bacteremia was also similar among patients undergoing diagnostic procedures and patients undergoing therapeutic procedures, but all cases of cholangitis occurred in the latter group (0 vs. 10%, respectively; P = .002). Nevertheless, the rate of cholangitis was not significantly changed by the use of prophylaxis (14% among treated patients vs. 5% among controls, P = .12). Therefore, infectious complications could not be prevented by cefonicid prophylaxis.
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PURPOSE: Mast cells have recently been found to be well correlated with the prognosis of patients with rectal cancer. This work aimed to characterize the role of mast cells in colonic premalignant conditions. METHODS: Mast cells were quantified in various colonic disorders, particularly those with premalignant potential. Possible avenues of mast cell action were investigated using these tissue samples, by measuring basement membrane and collagen layer thickening. RESULTS: The mean number of mast cells in carcinoma sections was 0.967/0.9 mm2, in various colorectal neoplasias and related conditions it ranged from 1.36-3/0.9 mm2, and in normal histologic specimens it was 11.90/0.9 mm2. These data established statistically significant differences in mast cell numbers in the colonic disorders studied. The number of mast cells is greatest in the lamina propria level of the colon, a site often not examined because of the limited depth of samples obtained from endoscopic biopsies. CONCLUSIONS: Mast cell numbers were found to be correlated to the development from premalignancy to colonic malignancy. Mast cells may be useful as markers of colorectal neoplasia.
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Perianal involvement in Crohn's disease is common (< or = 50%), distressing, and frequently refractory to treatment. Clinical features include painful induration and stenosis, discharging fistulas, and fissures. The pathogenesis of these lesions is unclear, but local ischemia and secondary anaerobic infection may play a role. Following three sporadic reports of successful treatment with hyperbaric oxygen (HBO), we undertook a trial of this method in 10 patients with refractory perianal disease. These patients' perianal Crohn's disease had not responded to treatment that included local medications, salicylates, corticosteroids, metronidazole, or 6-mercaptopurine were treated. Treatment was administered in a hyperbaric chamber at a pressure of 2.5 atm absolute. Each session lasted 90 min, and each course consisted of 20 daily sessions. Complete healing occurred in 5 patients after one to two courses. In an additional 2, after three courses, 1 patient improved but did not heal, and 2 did not improve. No adverse effects were noted by any of the 10 patients. Follow-up of 18 months did not reveal any recurrence. These preliminary results confirm that HBO therapy is a safe and efficient therapeutic option for perianal Crohn's disease.
A variety of evidence has pointed to immunological involvement in the pathogenesis of alopecia areata (AA). The aim of the present study was to determine whether differential expression of HLA-DR and intracellular adhesion molecules-1 (ICAM-1) occurs in hair structures of patients with longstanding AA, following stimulation with interferon-gamma (IFN-gamma). IFN-gamma was injected i.v. to nude mice grafted with transplants obtained from affected areas of seven patients and of normal individuals. All mice were injected with IFN-gamma or phosphate-buffered saline (PBS) alone for 3 consecutive days. Immunohistochemical studies were performed in specimens of grafts in order to detect the change in adhesion molecules, HLA-DR antigen, and Langerhans cells. ICAM-1 and HLA-DR induction was found to be similar in grafts from AA patients and normal skin grafts in the IFN-gamma injected mice. However, more intraepithelial Langerhans cells were observed in the AA patients' grafts treated with IFN-gamma than in those treated with PBS and in normal grafts treated with IFN-gamma. This study suggests an important role of Langerhans cells in this issue.
Increased expression of class II antigens (HLA-DR, human:Ia murine) on epithelial cells (EC) such as keratinocytes and gut EC suggests a role of the epithelium in the inflammatory response. It has been shown that injection of normal mouse serum (NMS) into nude mice caused an induction of Ia antigen by keratinocytes of the nude mice. The aim of the present study was to determine whether such induction could be observed in gut EC and whether it can be inhibited by cyclosporine A (CyA). Forty nude mice were divided into 4 groups of 10 each, designated A-D. Group A was injected with 0.1 ml of NMS; groups B and C were also injected with NMS and treated with oral CyA for 10 days. The dosage in group B was 30 g/ml and in group C 60 g/ml of drinking water. Group D was injected with serum of nude mice and served as a control group. Biopsies of small intestine and colon were obtained from each mouse and analyzed by indirect immunoperoxidase to identify Ia expression. Small intestine and colon EC were induced to express Ia antigen in most of the mice in groups A and B. A striking reduction in Ia expression was noted in group C. The differences between groups A and C concerning Ia expression on small intestine and colon EC were statistically significant. Our results demonstrate that the nude mouse may serve as a model for the study of Ia expression on gut EC, and that CyA can suppress the expression of Ia antigen also in the gut.
The prevalence of musculoskeletal system complaint and involvement in a group of 54 Crohn's disease patients, with a follow-up of 2 to 40 years, was studied and compared to that of a control group of patients with a similar distribution of sex and age. Twenty-four (44%) with Crohn's disease complained of arthralgia in various joints, but only 7.4% had objective findings compatible with joint pathology such as swelling, tenderness, and decreased range of motion. None of them had any serological or radiological evidences of joint damage. No significant correlation was found between patients' complaints/physical signs and age, sex, duration, or severity of Crohn's disease or mode of medical or surgical treatment. In the control group, 46% complained of arthralgia in various joint. The differences in the percentages of arthralgia between the two groups was not significant, although they differed in location of the affected joint. In the Crohn's disease group, a significantly higher proportion of knee, hip, and wrist involvement was observed, while backache was very common in the control group. It is suggested that arthritis in patients with Crohn's disease is an uncommon finding and that arthralgia is just as prevalent as in a matched control group. The pathogenesis of arthralgia in such a condition may be caused by soft tissue involvement.
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A 24-year-old woman who had immigrated from India 3 years before was referred because of diarrhea, abdominal pain and weight loss. Crohn's disease was suspected, but investigation revealed active pulmonary tuberculosis and tuberculosis of the small and large intestine. She was treated with rifampicin, 600 mg/day, INH 300 mg/day, and ethambutol, 400 mg/day, and recovered fully within 6 months.