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Biomedical subjects

Z Cohen

Publications and source records attributed to Z Cohen.

At least 73 records · Page 4Linked to original sources

An approach to perirectal disease in inflammatory bowel disease.

The management of perirectal disease in association with IBD requires an individual approach to the patient with combined medical and surgical therapy where appropriate. No matter what therapy is used, the main goal is to alleviate symptoms and cure the problem where possible. Before undertaking management it is crucial to delineate the extent not only of the local disease but the total extent of the problem in the gastrointestinal tract. This will obviously influence the way in which the local disease is managed. What has been presented is a practical, common-sense approach to the management of what is often an extremely difficult problem.

Female↗

Cost comparison of predictive genetic testing versus conventional clinical screening for familial adenomatous polyposis.

BACKGROUND: Mutations of the APC gene cause familial adenomatous polyposis (FAP), a hereditary colorectal cancer predisposition syndrome. AIMS: To conduct a cost comparison analysis of predictive genetic testing versus conventional clinical screening for individuals at risk of inheriting FAP, using the perspective of a third party payer. METHODS: All direct health care costs for both screening strategies were measured according to time and motion, and the expected costs evaluated using a decision analysis model. RESULTS: The baseline analysis predicted that screening a prototype FAP family would cost $4975/ pound3109 by molecular testing and $8031/ pound5019 by clinical screening strategy, when family members were monitored with the same frequency of clinical surveillance (every two to three years). Sensitivity analyses revealed that the genetic testing approach is cost saving for key variables including the kindred size, the age of screening onset, and the cost of mutation identification in a proband. However, if the APC mutation carriers were monitored at an increased (annual) frequency, the cost of the genetic screening strategy increased to $7483/ pound4677 and was especially sensitive to variability in age of onset of screening, family size, and cost of genetic testing of at risk relatives. CONCLUSIONS: In FAP kindreds, a predictive genetic testing strategy costs less than conventional clinical screening, provided that the frequency of surveillance is identical using either strategy. An additional significant benefit is the elimination of unnecessary colonic examinations for those family members found to be non-carriers.

Adenomatous Polyposis Coli↗

[Is there justification for limited percutaneous surgical drainage in severe neonatal necrotizing enterocolitis in low birth weight premature infants?].

The usual treatment of complicated neonatal necrotizing enterocolitis (NEC) is resection of the necrotic bowel, lavage of the peritoneal cavity and diversion enterostomy. Low-birth-weight premature neonates with this condition are in special danger if general anesthesia and full exploratory surgery is contemplated. A relatively simple alternate procedure is percutaneous insertion under local anesthesia of a soft abdominal drain, most often in the right lower quadrant. The procedure is done in the neonatal intensive care unit without moving the whole set-up to the operating room. 4 such cases have been treated within the past year. 3 were discharged home as they did not require additional surgical treatment, not having developed intestinal stenosis or obstruction. 1 recovered from the acute episode, but succumbed to a severe intraventricular hemorrhage and respiratory failure 7 days after the procedure. Our limited but most gratifying experience, in addition to similar experience of others, encourages us to recommend this simple surgical approach in the very sick low-birth-weight premature with fulminant NEC.

Abdomen↗

Tissue plasminogen activator (tPA) inhibits interleukin-1 induced acute lung leak.

Because plasminogen activators (PA) may participate in the inflammatory process associated with the acute respiratory distress syndrome (ARDS), we measured the effect of tissue plasminogen activator (tPA) on inflammation and acute lung leak caused by intratracheal instillation of IL-1alpha (50 ng) into male (300-400 g) Sprague-Dawley rats. Lung leak, lung myeloperoxidase (MPO) activity, and lung lavage neutrophil counts were increased in rats given IL-1 intratracheally compared to control rats that were given saline intratracheally. Giving tPA (12 mg/kg) intraperitoneally increased lung tPA concentration and reduced acute lung leak in rats given IL-1 intratracheally (p < .01; lung leak index for sham-treated rats: 0.040 + 0.001, n=6; IL-1: 0.10 + 0.01, n=10; tPA + IL-1: 0.050 + 0.002, n=6). In contrast, administering tPA did not change IL-1-induced increases in lung lavage neutrophils or lung MPO activity (sham: 0.003 x 106 + 0.001 x 10(6) cells; IL-1: 2.9 x 10(6) + 0.4 x 10(6) cells; tPA + IL-1: 2.7 x 10(6) + 0.4 x 10(6) cells; and sham: 0.6 + 0.2 U/g lung; IL-1: 11.2 + 2.9 U/g lung, tPA + IL-1: 11.1 + 1.6 U/g lung, respectively). Our results suggest that intraperitoneal tPA administration increases lung tissue tPA levels and decreases acute lung leak without reducing lung neutrophil infiltration in rats given IL-1alpha intratracheally. This work suggests that tPA may suppress neutrophil activation in vivo and accordingly have anti-inflammatory effects.

Animals↗

Differential regulation of rejection of small intestinal and skin allografts in rats by injection of antibodies to ICAM-1 or the integrins alpha 4, alpha L, or beta 2.

Female Lewis (LEW) rats received orthotopic small intestinal transplantation (SIT), or tail skin grafts from female (Lewis x Brown Norway)F1 (LBNF1) rats, along with peritransplant portal venous (pv) infusion of LBNF1 bone marrow-derived dendritic cells derived from male donors. All animals received im injection with cyclosporin A (5 mg/kg) for 3 consecutive days following transplantation. In some cases rats received intravenous injections, at 2-day intervals, with 1 mg of monoclonal antibodies to ICAM-1 or the integrins alpha 4, alpha L, or beta 2, or combinations of these reagents. Cells were harvested from the recipient rats at different times posttransplantation, and single cell suspensions were analyzed by FACS for expression of CD3+, CD4+, CD8+, alpha beta TcR+, and gamma delta TcR+ cells. Other tissue samples were used for histopathological assessment of rejection. We also investigated donor-specific and third-party (Wistar-Furth, Wi) restimulation of host lymphocytes from MLN, PLN, and PP for production of different cytokines in vitro. Of the various antibodies tested, only anti-alpha 4, but not anti-alpha L, -beta 2, nor -ICAM-1 led to further increased graft survival of LBNF1 SIT beyond that seen with pv-infused cells alone (30 days vs 19 days), while the combination of anti-alpha L (or beta 2) and ICAM-1 produced further significantly increased survival of skin grafts (30 days vs 21 days). For both SIT and skin-grafted animals increased graft survival was associated with decreased production of IL-2 and IFN-gamma and increased production of IL-4 and IL-10 from tissues local to the graft (PP and draining LN, respectively), with less significant alterations in tissues distant to the graft (PLN for SIT, and MLN for skin grafts). While, as reported previously, pv-immunized SIT rats showed increased gamma delta TCR+ cells within the SIT in association with increased graft survival, treatment with anti-alpha 4 diminished this increase in gamma delta TCR+ cells, while simultaneously increasing SIT survival. Nevertheless, the bias toward increased IL-10 production, and decreased IFN-gamma production, from cells of animals showing increased survival was maintained. These data suggest that local graft infiltration with gamma delta TCR+ cells following pv immunization is not necessary for prolongation of survival in this model system, although functional changes in the local cytokines milieu may be important.

Animals↗

Chronic intussusception in childhood.

A rare case of chronic intussusception is reported. Radiological investigation including ultrasound, CT and barium enema provided the correct diagnosis. Ultrasound revealed a solid mass near the transverse colon in the right lower abdomen. CT demonstrated the real nature of the solid mass as being the classical 'coiled spring' of intussusception. The barium enema was unsuccessful as an attempt at hydrostatic reduction, but confirmed the diagnosis by a 'crescent-shaped' filling defect in the ascending colon. The patient was discharged after an uneventful surgery and recovery. No organic lesion that precipitated the chronic intussusception was discovered at operation. Radiological findings, the typical clinical picture and adequate treatment are discussed.

Chronic Disease↗

Absence of linkage between inflammatory bowel disease and selected loci on chromosomes 3, 7, 12, and 16.

BACKGROUND & AIMS: Linkage data derived from genome-wide scans of inflammatory bowel disease (IBD) sibling-pair families have identified 4 loci on chromosomes 3, 7, 12, and 16 as potential sites for IBD susceptibility genes. The aim of this study was to investigate whether linkage analysis of another independently collected set of sibling pairs with IBD would provide further evidence of linkage between these previously reported loci and IBD. METHODS: Using the MAPMAKER/SIBS program, the segregation of 21 microsatellite marker loci spanning the 4 putative IBD gene loci was analyzed in a study population comprising 161 families with 114 Crohn's disease, 36 ulcerative colitis, and 50 mixed IBD sibling pairs from the Greater Toronto area. RESULTS: The results of multipoint linkage analysis showed no evidence for linkage between IBD and each of the 21 marker loci studied; the logarithm of odds scores in all instances were less than 0.8. These linkage data were found, by exclusion mapping analysis, to exclude values of lambdas ranging from 1.5 to 3.0, depending on the locus evaluated. CONCLUSIONS: The loci previously suggested as representing IBD susceptibility loci are not linked to IBD in the Toronto population examined in this analysis.

Chromosome Mapping↗

Thoracoscopic upper thoracic sympathectomy for primary palmar hyperhidrosis--the combined paediatric, adolescents and adult experience.

OBJECTIVE: To present our experience, over the past 4 years, of thoracoscopic upper thoracic sympathectomy in patients with primary palmar hyperhidrosis. DESIGN: Retrospective study. SETTING: University hospital, Israel. SUBJECTS: 402 thoracoscopic upper thoracic sympathectomies in 223 patients over a period of 4 years. INTERVENTIONS: Thoracoscopic ablation of ganglia and severing of the sympathetic chain at the level of T2 and T3. 142 patients underwent bilateral simultaneous sympathectomy, 37 had bilateral non-simultaneous sympathectomy and 44 had unilateral sympathectomy. RESULTS: 220 patients (98.7%) had an uneventful postoperative course and were discharged the following day. Three patients with residual pneumothorax required intercostal drainage and were discharged on the third postoperative day. 219 patients (98.2%) were completely satisfied, having immediate and permanent relief of palmar sweating. Four patients were dissatisfied. CONCLUSION: The thoracoscopic approach to the upper thoracic sympathectomy is at present the procedure of choice. Early operation for severe palmar hyperhidrosis is indicated to save a child many years of frustration and discomfort.

Adolescent↗

Genotype-phenotype correlations in attenuated adenomatous polyposis coli.

Germ-line mutations of the tumor suppressor APC are implicated in attenuated adenomatous polyposis coli (AAPC), a variant of familial adenomatous polyposis (FAP). AAPC is recognized by the occurrence of <100 colonic adenomas and a later onset of colorectal cancer (age >40 years). The aim of this study was to assess genotype-phenotype correlations in AAPC families. By protein-truncation test (PTT) assay, the entire coding region of the APC gene was screened in affected individuals from 11 AAPC kindreds, and their phenotypic differences were examined. Five novel germ-line APC mutations were identified in seven kindreds. Mutations were located in three different regions of the APC gene: (1) at the 5' end spanning exons 4 and 5, (2) within exon 9, and (3) at the 3' distal end of the gene. Variability in the number of colorectal adenomas was most apparent in individuals with mutations in region 1, and upper-gastrointestinal manifestations were more severe in them. In individuals with mutations in either region 2 or region 3, the average number of adenomas tended to be lower than those in individuals with mutations in region 1, although age at diagnosis was similar. In all AAPC kindreds, a predominance of right-sided colorectal adenomas and rectal polyp sparing was observed. No desmoid tumors were found in these kindreds. Our data suggest that, in AAPC families, the location of the APC mutation may partially predict specific phenotypic expression. This should help in the design of tailored clinical-management protocols in this subset of FAP patients.

Adenomatous Polyposis Coli↗

Reconstructive surgery for pelvic pouches.

Restorative proctocolectomy with ileo-pouch-anal anastomosis has become the elective surgical procedure of choice for most of our patients with ulcerative colitis and for selected patients with familial adenomatous polyposis. This report reviews the results of the outcome of patients who have undergone a more radical reconstructive approach for salvage of the pelvic pouch where multiple local procedures have failed. A group of 24 patients were reviewed (19 females, 5 males). The indication for surgery was ulcerative colitis in 22 patients; 10 of the 24 patients were referred from other centers. The 24 patients underwent a mean of 2.9 local salvage procedures per patient. Of the 19 females within the group, 12 had an anastomotic vaginal fistula. The 24 patients were divided into two groups. The first group consisted of 14 patients whose initial pouch was used once again for revisionary surgery. Group 2 comprised 10 patients whose initial pouch was removed and a redo pouch was constructed. Of the 24 patients, only 2 have had their pouches removed. More than 75% of the patients have had a successful outcome using a reconstructive approach. Four patients still have an ileostomy; of these four, two are awaiting closure of their loop ileostomy. Of 18 patients who were evaluable, 13 were considered to have normal daytime continence, and 17 of 18 were sexually functional. Of the 18 evaluable patients, 15 were satisfied with the outcome. Radical reconstructive surgery can be performed where local procedures to effect pouch salvage have failed, and it should be considered as a first-line management where factors dictate that local procedures might fail. The commitment of the surgeon and the patient to achieving a successful outcome is essential. Severe pouch-specific complications can be managed successfully by surgeons who have a specific interest in pelvic pouch surgery and have considerable experience dealing with complications that arise.

Adolescent↗

Surgical management of acquired rectourethral fistula, emphasizing the posterior approach.

Rectourethral fistula is an uncommon surgical entity having a variety of congenital and acquired causes. Although several surgical approaches have been proposed in the literature, successful repair is often difficult. The 2 patients described had rectourethral fistulas after radical prostatectomy. One patient failed previous transabdominal and perineal repairs. The authors propose a 3-step approach to management of acquired rectourethral fistulas. A diverting transverse colostomy with insertion of a suprapubic or indwelling silicone rubber Foley catheter for 3 to 6 months will allow for a decrease in the inflammatory response surrounding the involved area and possible spontaneous closure. If spontaneous closure does not occur within this time, the fistula should be closed operatively through a posterior approach (modified York-Mason procedure). This approach provides excellent exposure and allows the suture lines to be offset, which in turn allows for better healing, present a minimal risk of impotence or incontinence and allows for complete separation of urinary and fecal streams. The third step involves closure of the colostomy followed by removal of the Foley or suprapubic catheter if there is no recurrence. Timing of this step is crucial and should be individualized according to the postoperative course.

Aged↗

Familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC): a review of clinical, genetic and therapeutic aspects.

Familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC) are two syndromes of colorectal cancer predisposition, inherited in an autosomal dominant fashion. They account for about 1% and 5-7% of all colorectal cancer cases, respectively. FAP is caused by germline mutations of a tumour suppressor gene, the adenomatous polyposis coli (APC) gene, whereas HNPCC results from genetic alterations of the DNA mismatch repair genes. Clinical manifestations in FAP include colonic as well as extracolonic sites (duodenum, eye, dental, nervous or connective tissues). In FAP, prophylactic colectomy is required in all affected patients and regular endoscopic check-up of the upper gastrointestinal tract is necessary to detect malignant transformation of duodenal polyps; medical management of complex desmoid tumours is preferred rather than surgery. In HNPCC, there are extracolonic associated endometrial, gastric, small bowel or brain carcinomas. At present time, for HNPCC patients, only preventive measures such as regular colonoscopic or gynecologic examinations are recommended, since prophylactic colectomy or hysterectomy are not considered to be routine procedures.

Adenomatous Polyposis Coli↗

Fatty acid unsaturation in the red alga Porphyridium cruentum. Is the methylene interrupted nature of polyunsaturated fatty acids an intrinsic property of the desaturases?

Polyunsaturated fatty acids (PUFAs) exogenously supplied to the red microalga Porphyridium cruentum were incorporated into cellular lipids. All the C18 PUFAs studied were desaturated by a delta 6-desaturase and all the C20 PUFAs by a delta 5-desaturase. The latter enzyme desaturated even 20:2(11, 14) to 20:3(5, 11, 14) and 20:3(11, 14, 17) to 20:4(5, 11, 14, 17). We infer the existence of several fatty acid desaturases, with different chain length specificities. Furthermore, the introduction of double bonds in a methylene interrupted pattern, at least for alpha-type desaturase such as the delta 5- and delta 6-desaturases, is not an intrinsic property of the enzyme but a consequence of the arrangement of the pre-existing double bonds in the fatty acid substrate.

Eukaryota↗

Laparoscopic and thoracoscopic surgery in children and adolescents: a 3-year experience.

Our initial experience over the last 3 years with laparoscopic and thoracoscopic surgery in children and adolescents is reported. Between September 1992 and August 1995, a total of 215 laparoscopic and thoracoscopic procedures were performed: 32 appendectomies for acute appendicitis, 10 cholecystectomies for symptomatic gallstones, 11 procedures for adnexal pathology, 6 laparoscopies in children with nonpalpable testes, 3 diagnostic laparoscopies, and 153 thoracoscopic sympathectomies in children suffering from primary palmar hyperhidrosis. The post-operative course was uneventful in all cases. In 2 children with acute appendicitis we converted to the open technique due to technical difficulties. We are encouraged by the results of our initial experience. There is no doubt that laparoscopic cholecystectomy, laparoscopic surgery of adnexal pathology, and thoracoscopic sympathectomy, because of their numerous benefits - shorter operative time, hospitalization, and convalescence as well as less postoperative pain and improved cosmetic results - are replacing the open techniques. We are not convinced as yet of the advantages of laparoscopic appendectomy in children; we are presently performing both laparoscopic and conventional techniques and studying the various parameters in order to reach a more definite conclusion. Various other endoscopic surgical procedures will be carefully considered in the near future.

Acute Disease↗

Necrotizing fasciitis and myonecrosis in early childhood: a report of three patients.

Necrotizing fasciitis (NF) is a rare and life-threatening disease. It usually presents as a postoperative complication, but rarely appears following trauma or without apparent cause. Over a period of 2 years we have treated three infants with NF, aged 15, 5, and 30 months, respectively. Two patients developed this complication following minor trauma while the third was post-elective bilateral inguinal hernia repair. The micro-organisms isolated were Staphylococcus aureus with Enterococcus durans in one patient, beta-hemolytic streptococcus in a second, and Staph. aureus in the third. The cornerstone of therapy is prompt, early, aggressive surgical debridement of the massive necrotic tissue and repeated debridement if necessary, with appropriate parenteral antibiotic therapy and hyperalimentation. All three patients survived. Early recognition of this life-threatening situation is mandatory in achieving survival.

Anti-Bacterial Agents↗

Risk factors for pelvic pouch failure.

PURPOSE: This study was designed to identify factors associated with pelvic pouch failure. METHOD: A retrospective review of patients undergoing the pelvic pouch procedure with a minimum of 30 months follow-up was conducted. RESULTS: A total of 551 patients had pelvic pouch procedures from 1981 to 1992. Forty-nine patients (8.8 percent) have undergone pouch excision, and 9 (1.6 percent) have been defunctioned, for 58 (10.5 percent) patients with pouch failure. Cause of failure was leakage from the ileoanal anastomosis (IAA) in 21 (39 percent) patients, poor functional results in 13 (23 percent), pouchitis in 7 (12 percent), pouch leakage in 7 (12 percent), perianal disease in 7 (12 percent), and miscellaneous in 3 (5.2 percent). Nine of 22 patients (41 percent) had pouch failure during the first two years, with 2 of 147 patients (1 percent) having failure during the last two years of the study. The 58 patients whose pouches failed (Group 1) were compared with the 493 patients whose pouches did not fail (Group 2). Handsewn IAA (P < 0.001), tension on the IAA (P < 0.001), use of a defunctioning ileostomy (P < 0.01), a diagnosis of Crohn's disease (P < 0.001), and a leak from the pouch (P < 0.001) or the IAA (P < 0.001) were associated with pouch failure. Pouchitis was not a risk factor. CONCLUSION: The majority of pouch failures were caused by leaks at the IAA. Although the leak rate remained stable, leaks following a stapled anastomosis seemed to have a better prognosis than leaks following a handsewn anastomosis. Experience with the pouch procedure and the management of complications likely plays an important role in decreasing the risk of pouch failure.

Adult↗

Using genetic information to make surgical decisions: report of a case of a 13-year-old boy with colon cancer.

PURPOSE: We report the case of a boy aged 13 years who was diagnosed with a Dukes B obstructing cancer of the sigmoid colon. At the time of diagnosis, he underwent a Hartmann's procedure with end colostomy. Because of his unusually young age, he was referred to the Familial GI Cancer Registry at Mount Sinai Hospital for genetic assessment. A detailed pedigree revealed no significant history other than lung cancer in his maternal grandfather. METHODS: We obtained his tumor specimen and performed molecular analysis of both normal colonic and tumor DNA. Specifically, we identified replication errors (RER) in the patient's tumor DNA when compared with normal colonic DNA. RER has been found in more than 90 percent of tumors from patients with Hereditary Nonpolyposis Colon Cancer (HNPCC) and is, thus, considered to be one of the hallmarks of this disease. Because HNPCC patients have a 40 percent risk of synchronous or metachronous tumors, the recommended surgery for HNPCC should be at least a subtotal colectomy with ileorectal anastomosis. RESULTS: Based on molecular results, we were able to recommend that the patient have a subtotal colectomy performed instead of merely colostomy closure, to reduce his lifetime risk of developing further colon tumors and to make surveillance of the remaining rectum relatively easy. In this patient, we subsequently identified a germline mutation of the mismatch repair gene hMSH2 that is implicated in HNPCC. The possibility of HNPCC should be considered in adolescents who are diagnosed with colorectal cancer, so appropriate surgical decisions can be made.

Adenocarcinoma, Mucinous↗