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Z Cohen

Publications and source records attributed to Z Cohen.

At least 19 recordsLinked to original sources
PubMed2006

Mouse major satellite DNA is prone to eccDNA formation via DNA Ligase IV-dependent pathway.

Elevated levels of extrachromosomal circular DNA (eccDNA or spcDNA) are closely associated with genomic instability and aging. Despite extensive studies, the mechanism of its generation in mammalian cells is unknown. We report here that mouse major satellite DNA (MSD) is prone to eccDNA formation and that the resulting molecules are multimeres of the basic repeat. Extrachromosomal circular major satellite (ECMS) DNA constitutes the majority of eccDNA in B16 mouse melanoma cells and is highly abundant in other mouse cells. Production of these molecules is enhanced in proliferating cells, suggesting that processes associated with DNA replication are involved in their appearance. Using siRNA technique we show that DNA Ligase IV is engaged in ECMS synthesis. Based on our findings we propose a novel two-step model for eccDNA formation in mammalian cells.

Animals↗
PubMed2006

Increased experience and surgical technique lead to improved outcome after ileal pouch-anal anastomosis: a population-based study.

PURPOSE: This study was designed to determine whether changes in length of stay and 30-day readmission, reoperation, and excision rates for the ileal pouch-anal anastomosis occurred over time and with changes in surgical technique and hospital volume. METHODS: Using three population-based administrative databases, data on all ileal pouch-anal anastomoses performed in the province of Ontario between January 1992 and June 1998 were obtained. The effect of age, gender, stage of the procedure, year of surgery, and hospital volume were examined for their effect on length of stay and readmission, reoperation, and excision rates. RESULTS: There were 1,285 ileal pouch-anal anastomoses performed in 58 hospitals. There was a significant decrease in length of stay and reoperation and excision rates but a concommitant increase in readmission rate during the study period. Patients younger than aged 40 years had a significantly lower length of stay and excision rate. Patients who had a two-stage procedure had a shorter length of stay, readmission, and reoperative rate compared with those having a three-stage procedure. Hospital volume was a significant predictor of need for reoperation and excision with both low-volume and medium-volume hospitals having significantly higher rates than high-volume hospitals. CONCLUSIONS: Outcome after ileal pouch-anal anastomosis has improved. It is significantly better in patients younger than aged 40 years, having a two-stage procedure, and where surgery is performed at high-volume hospitals. It is likely that both modifications in surgical technique and surgical experience have led to improvements in clinical outcome after ileal pouch-anal anastomosis.

Adult↗
PubMed2006

The latest is the greatest? Results of a structured lecture about aromatase inhibitor use for breast cancer.

BACKGROUND: The aromatase inhibitors (AIs) are increasingly surpassing tamoxifen as the endocrine treatment of choice for postmenopausal breast cancer patients. With their increasing use, there is concern that they are being inadvertently prescribed to pre- and peri-menopausal women. METHODS: As part of a continuing medical education program for 264 practicing surgeons, a 15-min lecture was given over viewing hormone therapy for early stage breast cancer. Two multi-choice questions were asked before and after the lecture regarding the optimal hormonal treatment for pre and postmenopausal women. RESULTS: For the optimal treatment of premenopausal women, 36% of respondents chose tamoxifen before the lecture, rising to 82% after it (p<0.01). However 37% suggested an AI would be best, with a further 27% choosing either an AI or tamoxifen, falling to 7% and 11% respectively after the lecture. Before the lecture, 30% of the participants stated that any of the listed treatment options; tamoxifen alone, an AI alone or a combination of tamoxifen and an AI would be acceptable for postmenopausal women. Following the lecture, 53% chose this option (p<0.01). CONCLUSIONS: In many countries it is practicing surgeons who commence endocrine therapy for patients with breast cancer. The findings of this study are useful from two points. Firstly it is clear that many physicians feel that AIs are an effective adjuvant endocrine therapy for premenopausal breast cancer. Secondly it demonstrates the benefits of continuing medical education as a significant improvement in test scores was noted after a structured lecture.

Aromatase Inhibitors↗
PubMed2005

Family history and molecular features of children, adolescents, and young adults with colorectal carcinoma.

BACKGROUND: Colorectal cancer is extremely rare in childhood. Published case series reporting children and adolescents with colorectal cancer have not focused on the underlying genetic aspects of the tumour or genetic susceptibility of the families. AIMS: We examined a cohort of patients with early onset colorectal cancer to determine whether a specific genetic predisposition could be elucidated. In particular, we focused on whether DNA mismatch repair gene deficiency which causes hereditary non-polyposis colorectal cancer (HNPCC) could be elucidated. METHODS: Patients with colorectal cancer </=24 years of age were identified from a database at the Familial Gastrointestinal Cancer Registry at Mount Sinai Hospital, Toronto. Detailed pedigrees were ascertained from the proband or parents. Tumours were tested for microsatellite instability, a hallmark of HNPCC. Germline mismatch repair gene mutations (MSH2 and MLH1) were sought in some cases. Clinical data were obtained by chart audit. RESULTS: Among 1382 probands in our registry, 16 (1%) colorectal cancer patients were 24 years or younger at the time of diagnosis. Microsatellite instability was identified in tumours from eight (73%) of 11 evaluated patients. Germline mutations in mismatch repair genes were identified in six of 12 patients, including MSH2 (n = 3), MLH1 (n = 2), and PMS2 (n = 1). Ten (63%) of 16 families met the Amsterdam criteria for HNPCC. Among these, six were screened for mismatch repair gene mutations and three were found to carry MSH2 or MLH1 germline mutations. Location of the colorectal cancers included rectum/sigmoid (n = 9), splenic flexure (n = 2), hepatic flexure (n = 3), and caecum (n = 2). Forty four per cent (7/16) of these young cases developed additional malignancies (gastrointestinal (n = 8) and extraintestinal (n = 4)) during follow up (mean 12.8 (SD 12.4) years (range 0.08-30)). CONCLUSIONS: Patients with early onset colorectal carcinoma often have an inherited predisposition to the disease. Tumours with high frequency microsatellite instability and germline mutations of mismatch repair genes are sufficiently common in this patient population that they should be considered, even though family histories may not satisfy the stringent Amsterdam criteria for HNPCC. Young colorectal cancer patients are at increased risk of developing second gastrointestinal and extraintestinal malignancies.

Adolescent↗
PubMed2004

Laparoscopically guided distal ventriculoperitoneal shunt placement.

In standard techniques for performing ventriculoperitoneal shunts, the peritoneal catheter is threaded more or less blindly into the peritoneal cavity. Using laparoscopic techniques allows accurate peritoneal placement, without a large incision, even in replacement procedures and in patients with previous abdominal operations. We performed 28 laparoscopically guided ventriculoperitoneal shunt placements and shunt revisions in 24 patients with hydrocephalus (aged 6-80 years). Sixteen of 24 patients (67%) had previous abdominal surgery. Laparoscopic shunt placement was successful in all patients. Mean operative time was 63 +/- 34.9 minutes (range 15-150 minutes). In 2 patients, broken and disconnected distal parts of previously inserted shunts were removed from the abdomen. One shunt was removed following infection and other one was revised due to shunt malfunction. Three patients required revision of the cranial part of the shunt. Laparoscopically guided distal ventriculoperitoneal shunt placement provides definite patient benefits: it allows shunt placement under direct vision, associated with reduced trauma to the abdominal wall, and avoids a consequent risk of intra-abdominal adhesions.

Adolescent↗
PubMed2003

Outcome of patients undergoing liver transplantation for primary sclerosing cholangitis.

PURPOSE: The purpose of this study was to determine the outcome of patients with inflammatory bowel disease who underwent liver transplantation for primary sclerosing cholangitis. METHODS: All patients who underwent liver transplantation for primary sclerosing cholangitis at our institution were identified. A review of patients' hospital and office charts was performed; all patients were then contacted, and a detailed survey was administered by telephone. RESULTS: Sixty-nine patients were identified. There were 53 males (76.8 percent) and 16 females, with a mean age of 45.3 (+/- 13.3) years. Fifty-two (75.4 percent) of the 69 patients had documented inflammatory bowel disease; of these, 40 had ulcerative colitis (76.9 percent), 11 had Crohn's disease, and 1 had indeterminate colitis. Thirty-one patients (60 percent) were diagnosed with inflammatory bowel disease before primary sclerosing cholangitis, with a mean interval to diagnosis of primary sclerosing cholangitis of 10.8 (+/- 10.3) years. Seven patients had both diagnoses made at roughly the same time, and 14 patients initially were diagnosed with primary sclerosing cholangitis and subsequently were found to have inflammatory bowel disease, with a mean interval of 5.2 (+/- 4.4) years; 5 (35.7 percent) of those 14 patients were only diagnosed with inflammatory bowel disease after their liver transplant. The mean time from diagnosis of primary sclerosing cholangitis to liver transplantation was 6.1 (+/- 4.9) years. Since their transplant, 30.8 percent of patients rated their colitis as worse, 38.5 percent felt it was unchanged, and 30.8 percent felt that their colitis was better controlled. Eight (15.4 percent) of the 52 patients with inflammatory bowel disease denied having any knowledge of an increased risk of colorectal neoplasia. Four patients have required colectomy for colorectal neoplasia after liver transplantation, at a mean of 4.7 years after transplantation. Of the patients with inflammatory bowel disease, 42 (80.1 percent) had at least 1 posttransplant surveillance colonoscopy. Eight of the remaining ten patients had a colectomy, leaving only two patients (3.8 percent) who had not been surveyed. However, only 32 (61.5 percent) of the patients with inflammatory bowel disease have been on a surveillance regimen that would approximately conform to current screening recommendations. CONCLUSIONS: The activity of inflammatory bowel disease after transplantation is highly variable. Patients appeared to lack knowledge of their increased risk for colorectal neoplasia. Colorectal cancer is an uncommon but important complication in patients after liver transplantation for primary sclerosing cholangitis, and ongoing surveillance is required. Patients may require education to increase their awareness of the cancer risk and compliance with surveillance.

Chi-Square Distribution↗
PubMed2003

Revising the troublesome stoma: combined abdominal wall recontouring and revision of stomas.

PURPOSE: Despite preoperative siting and maturation of stomas, some patients may have poor stoma function because of redundant pannus, scars, creases, and parastomal or incisional hernias. In these patients, a combined abdominoplasty and stoma revision may be helpful. The object of this manuscript is to report our preliminary results. METHODS: Eight patients (mean age, 48 years; female/male ratio, 7/1) undergoing this procedure are reported. Five patients had inflammatory bowel disease, two had malignancies, and one had multiple sclerosis with bladder and bowel involvement. Patients were contacted at two months to two years follow-up to assess functional outcome and satisfaction with the procedure. RESULTS: Indications for surgery were difficulty maintaining an appliance (n = 7), frequent stool leakage (n = 6), and skin irritation (n = 4). Multiple surgeries (n = 4), skin creases (n = 3), scarring (n = 2), large weight loss (n = 4), and hernias (n = 5) were contributing factors. At surgery five patients had hernias repaired (3 parastomal, 2 incisional), three had stomas resited, and three underwent resections for Crohn's disease. One patient developed a seroma postoperatively. At follow-up six patients were able to maintain an appliance for at least four days, whereas one changed the appliance every three days because of personal preference. None experience stool leakage. All reported a dramatic improvement in body image. CONCLUSION: Combined stoma revision and abdominoplasty can be performed safely and leads to improved functional results and outcome.

Abdominal Muscles↗
PubMed2002

Pregnancy, delivery, and pouch function after ileal pouch-anal anastomosis for ulcerative colitis.

PURPOSE: This study was designed to evaluate the pregnancies, method of delivery, and functional results of females with chronic ulcerative colitis who have an ileal pouch-anal anastomosis. METHODS: A mailed questionnaire was sent to all females with an ileal pouch-anal anastomosis for chronic ulcerative colitis. Information on the pregnancy, method of delivery, and outcome was collected. Those females who had a successful pregnancy and delivery were contacted by telephone to clarify results and determine pouch functional results. Other clinical information was obtained from the Mount Sinai Hospital Inflammatory Bowel Disease database. RESULTS: Thirty-eight subjects had 67 pregnancies. Of these, 29 subjects had 49 deliveries. There were 25 vaginal deliveries and 24 cesarean sections. There were two pouch-related complications during the pregnancies and four pouch-related complications postpartum. All were treated nonoperatively. Stool frequency and day and night incontinence were increased during pregnancy in most subjects, but after delivery, prepregnancy function was restored in 24 (83 percent) of them. Five subjects (17 percent) had some degree of permanent deterioration in pouch function. Of these, three had vaginal deliveries, and two had cesarean sections. Multiple births and birth weight were not found to adversely affect subsequent pouch function. CONCLUSION: Pregnancy is safe in females with ileal pouch-anal anastomosis. Functional results are altered almost exclusively during the third trimester, but pouch function promptly returns to prepregnancy status in most females. A small proportion of females have long-term disturbances in function, but these are not related to the method of delivery. Thus, the method of delivery should be dictated by obstetric considerations.

Adult↗
PubMed2002

Preduodenal portal vein causing duodenal obstruction associated with situs inversus, intestinal malrotation, and polysplenia: A case report.

Preduodenal portal vein (PDPV) is a rare anomaly described in only 82 patients in the literature. In a few patients, the PDPV was the direct cause of duodenal obstruction. The authors have treated a newborn with PDPV associated with total situs inversus, intestinal malrotation and polysplenia who presented clinically with duodenal obstruction.

Abnormalities, Multiple↗
PubMed2001

Adenomatous polyps develop commonly in the ileal pouch of patients with familial adenomatous polyposis.

PURPOSE: The aim of this study was to establish the prevalence of adenomatous polyps in the ileal pouch of patients with familial adenomatous polyposis. METHOD: Forty-three patients who had an ileal pouch for familial adenomatous polyposis were invited to have a careful endoscopic examination of their pouch, including dye spraying. The number of polyps was recorded, and up to ten were biopsied. In addition, four random biopsy specimens were taken from the proximal and four from the distal pouch. RESULTS: Thirty-three patients with a median age of 36 (range, 14-63) years who had a pouch (5 Kock and 28 pelvic) for a median of 7 (range, 1-19) years accepted the invitation. Twenty-one patients (64 percent) had endoscopically identified polyps, the number of polyps ranging from 1 to 100 (median, 10) and varying in size from 1 to 3 mm. Fourteen patients (42 percent) had adenomatous polyps and 4 of these also had microadenomas on random biopsies. Nine of the 14 patients with adenomas also had lymphoid polyps. Seven patients had lymphoid polyps only and two of these patients had a microadenoma on random biopsy. Four of 12 patients with no visible polyps had microadenomas in their random biopsies. The presence of adenomatous polyps (Pearson's correlation; P < 0.01) increased with the age of the pouch. In total, 20 of 33 (60 percent) patients had adenomas and or microadenomas. CONCLUSION: Adenomatous polyps occur frequently in ileal pouches. These findings are of concern, and therefore, regular surveillance seems warranted until the natural history of these adenomatous polyps is determined.

Adenomatous Polyposis Coli↗
PubMed2001

Extended follow-up of patients treated with cytotoxic chemotherapy for intra-abdominal desmoid tumors.

BACKGROUND: Cytotoxic chemotherapy can achieve a good initial response in inoperable desmoid tumors that have caused progressive obstruction of the gastrointestinal and urinary tracts and have caused unrelenting pain. METHODS: We have reviewed 8 patients (3 male) with desmoid tumors and familial adenomatous polyposis who underwent cytotoxic chemotherapy for inoperable gastrointestinal obstruction and/or uncontrolled pain. They were treated with doxorubicin and dacarbazine followed by carboplatin and dacarbazine. RESULTS: Follow-up after cytotoxic chemotherapy in the 7 patients for whom it was available was a mean of 42 (range 24-54) months. Two patients achieved complete remission after therapy. Four patients achieved a partial remission after completing all or some of the chemotherapy regimen; of these, three remained in stable remission, whereas the other was lost to follow-up. There were two recurrences that required further therapy; one of these patients was treated with further chemotherapy, which induced a second remission, and the other was treated with pelvic exenteration and has subsequently died. CONCLUSIONS: Most patients had a substantial response to cytotoxic chemotherapy; however, two patients required additional therapy 24 and 30 months after cytotoxic chemotherapy, respectively. Cytotoxic chemotherapy is effective in producing short-term and long-term remission in these difficult patients.

Adenomatous Polyposis Coli↗
PubMed2001

Carrier rate of APC I1307K is not increased in inflammatory bowel disease patients of Ashkenazi Jewish origin.

Colorectal cancer (CRC) occurs with an increased incidence in individuals with chronic inflammatory bowel disease (IBD) of the colon. Recent data suggest that a family history of colorectal cancer is an independent risk factor for CRC in IBD, an observation that implies that genetic factors are relevant to the development of CRC in this context. Among the genetic defects associated with CRC, the APC I1307K mutation has been detected nearly exclusively in individuals of Ashkenazi Jewish (AJ) origin, occurring in 6%-7% of the AJ general population and in 10%-28% of AJ with a either a personal or family history of CRC or adenomatous polyps. These findings, together with the increased incidence of IBD in AJ, prompted the current analysis of the contribution of the APC I1307K variant of CRC in AJ IBD patients. APC I1307K carrier frequencies were determined in 306 AJ individuals affected with IBD and 308 of their unaffected relatives ascertained from a family collection obtained for the identification of IBD susceptibility genes. Prevalence of the I1307K variant was not significantly different among individuals with IBD, Crohn's disease, ulcerative colitis, and unaffected relatives (6.9%, 7.6%, 4.7%, and 6.2%, respectively), and the mutation was detected in only one of five IBD-affected individuals with a diagnosis of CRC. These results reveal that IBD patients of AJ origin carry the APC I1307K variant at the same rate as individuals within the general AJ population. Lack of an increased APC I1307K carrier rate suggests that this mutation does not account for the increased CRC susceptibility associated with IBD.

Adult↗
PubMed2001

Familial history, age and smoking are important risk factors for disc degeneration disease in Arabic pedigrees.

The present study used computed tomography imaging to evaluate the extent and pattern of the intergenerational transmission of spinal disc degeneration disease (DDD) in complex pedigrees. Contribution of a number of the potential covariates was also studied using univariate and multivariate logistic regression analysis, as well as two types of complex segregation analysis models. Among 161 individuals studied, DDD was diagnosed in 60 individuals. The number of protruded discs varied from 1 to 4, mostly in lumbar or lumbosacral regions. The average age at onset of the disease was similar for both women (36.0 years) and men (34.8 years). The proportion of the individuals affected by the DDD status of their parents ranged from 10% in families of two healthy parents to 55.5% of two affected parents (p < 0.01). The results of the logistic regression analyses and complex segregation analysis were qualitatively the same: DDD status of parents, age and smoking were the main risk factors for disc herniation in the Arabic families we examined. All analyses showed a predominating role of the family history as a risk factor for DDD in offsprings. It showed, for example, four times higher risk at age 50 for individuals with two affected parents vs. those who have two non-affected parents. However, the results of models-fitting genetic analysis, did not confirm a monogenic Mendelian pattern of inheritance.

Adult↗
PubMed2001

Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease.

Linkage disequilibrium (LD) mapping provides a powerful method for fine-structure localization of rare disease genes, but has not yet been widely applied to common disease. We sought to design a systematic approach for LD mapping and apply it to the localization of a gene (IBD5) conferring susceptibility to Crohn disease. The key issues are: (i) to detect a significant LD signal (ii) to rigorously bound the critical region and (iii) to identify the causal genetic variant within this region. We previously mapped the IBD5 locus to a large region spanning 18 cM of chromosome 5q31 (P<10(-4)). Using dense genetic maps of microsatellite markers and single-nucleotide polymorphisms (SNPs) across the entire region, we found strong evidence of LD. We bound the region to a common haplotype spanning 250 kb that shows strong association with the disease (P< 2 x 10(-7)) and contains the cytokine gene cluster. This finding provides overwhelming evidence that a specific common haplotype of the cytokine region in 5q31 confers susceptibility to Crohn disease. However, genetic evidence alone is not sufficient to identify the causal mutation within this region, as strong LD across the region results in multiple SNPs having equivalent genetic evidence-each consistent with the expected properties of the IBD5 locus. These results have important implications for Crohn disease in particular and LD mapping in general.

Chromosome Mapping↗
PubMed2001

Osteopetrosis: a single centre experience of stem cell tranisplantation and prenatal diagnosis.

Malignant osteopetrosis (MOP) is an autosomal recessive disease in which osteoclast dysfunction results in excessive bone deposition and early infant death. Thirteen children suffering from MOP from four related families all belonging to one Bedouin tribe, were studied. The disease was diagnosed as early as at a few days postnatal to 5 months. Nine children underwent BMT, four of whom are still alive; one is blind and two have markedly reduced vision. Four children who did not undergo BMT died between 4 and 6 months of age. Recently, the gene for MOP has been mapped for this Bedouin tribe allowing prenatal diagnosis. Seven pregnancies were subsequently prenatally diagnosed and two fetuses were found to be affected. Pregnancy was electively terminated in one case. In the other case the parents refused and after establishing the diagnosis, the newborn was transplanted at the age of 7 days.

Adult↗