Ijaz Ahmed
Research interests
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InterestsLawyer
Publications
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2.09Impact points
Combined effect of menopause age and genotype on occurrence of breast cancer risk in Pakistani population.
Maturitas. 06/2011; 69(4):377-82.
Cancer incidences and mortality rates are rapidly increasing and breast cancer is among the most frequent malignancy experienced in women worldwide. The occurrence of breast cancer could be associated with various social, cultural, environmental, life-style, hormonal and genetic factors. To establis... [more] Cancer incidences and mortality rates are rapidly increasing and breast cancer is among the most frequent malignancy experienced in women worldwide. The occurrence of breast cancer could be associated with various social, cultural, environmental, life-style, hormonal and genetic factors. To establish if PvuII and XbaI polymorphisms of estrogen receptor alpha would make Pakistani women more susceptible to breast cancer. Furthermore, association between breast cancer and various factors was also explored to establish the contributing factors in breast cancer in Pakistani population. Two hundred samples, aged 15-65 years, consisting of 100 breast cancer patients and 100 control samples were ascertained for this case-control study in order to evaluate the factors related to disease incidence. 5-7 ml of blood sample of each participating women in the study was collected and analyzed for polymorphisms of PvuII and XbaI using PCR-RFLP method. The menopause had strong influence on incidences of cancer with ca 18-fold increase in risk of breast cancer in women with menopause compared with non-menopaused. Furthermore significant impact of menopause age (P<0.0001) was observed on the incidence of cancer, as high rate of cancer incidence was observed in patients with age between 36 and 45 years (P<0.0001). Similarly, the genotype XbaI had significant influence on the incidence of the disease with heterozygous genotype of XbaI was 45% higher than wild type in cancerous cases. The menopausal women having heterozygous and homozygous mutants of PvuII or XbaI genotypes were strongly correlated with breast cancer (P<0.01). The polymorphism of genes involving estrogen-metabolizing pathway and estrogen receptor pathway may play an important role in the etiology of breast cancer in Pakistani women.
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Frequency distribution of GSTM1 and GSTT1 null allele in Pakistani population and risk of disease incidence.
Environmental toxicology and pharmacology. 07/2010; 30(1):76-9.
Glutathione-S-transferases, GSTM1 and GSTT1 play a significant role in detoxification and bioactivation of a broad range of xenobiotic compounds known to be mutagenic and/or carcinogenic. Deletion polymorphisms of these glutathione transferases (GSTM1 and GSTT1) predispose individuals to environment... [more] Glutathione-S-transferases, GSTM1 and GSTT1 play a significant role in detoxification and bioactivation of a broad range of xenobiotic compounds known to be mutagenic and/or carcinogenic. Deletion polymorphisms of these glutathione transferases (GSTM1 and GSTT1) predispose individuals to environmental carcinogenic compounds. Although a number of studies have shown the relationship between GSTM1 and/or GSTT1 deletion polymorphism and different cancers, these findings cannot be extrapolated to other populations due to intra- and inter-ethnic variability. In order to assess the impact of differential ethnicity on the occurrence of different cancers in local population due to GSTM1, or GSTT1 deletion polymorphism, 111 healthy male and female individuals of different age groups from Southern Punjab, Pakistan were genotyped using a multiplex polymerase chain reaction. From the results it is obvious that null alleles of GSTM1 and GSTT1 genes were found in 45% and 23% individuals, respectively. In 5% of individuals' simultaneous deletion of both GSTM1 and GSTT1 genes were observed. Frequency of GSTM1 null allele is in concordance with those documented for Chinese, Caucasians, Mongolian, and Japanese populations. However, a significantly higher frequency for GSTT1 null was reported in Chinese and Japanese population as compared to Pakistani population. It is the first ever report on frequency of GSTM1 and GSTT1 null allele in Pakistani population which demonstrate the impact of ethnicity and provide basis for future epidemiological and clinical studies.
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6.71Impact points
Colonoscopic full-thickness resection of the colon in a porcine model as a prelude to endoscopic surgery of difficult colon polyps: a novel technique (with videos).
Gastrointestinal endoscopy. 08/2009; 70(1):159-65.
BACKGROUND: Colonoscopic full-thickness resection (CFTR) of the colon may obviate the need for surgical resection of benign lesions. OBJECTIVE: To develop an animal model for CFTR of the colon followed by endoscopic suture closure with through-the-endoscope devices. DESIGN: Pilot study. SETTING: Uni... [more] BACKGROUND: Colonoscopic full-thickness resection (CFTR) of the colon may obviate the need for surgical resection of benign lesions. OBJECTIVE: To develop an animal model for CFTR of the colon followed by endoscopic suture closure with through-the-endoscope devices. DESIGN: Pilot study. SETTING: University medical center. ANIMALS: Twenty pigs. INTERVENTIONS: A 2-cm circular area was resected on the antimesenteric side of the colon (phase 1, n = 10) and on the mesenteric side (phase 2, n = 10) by using an insulated tip knife cut followed by the use of a grasping forceps and a snare to resect and retrieve the specimen. The tissue apposition system was used to close the defect. MAIN OUTCOME MEASUREMENTS: Resection and closure times were recorded. The animals were euthanized at 2 weeks and examined for peritonitis, adhesions, wound healing, and T-tag injury to adjacent viscera. RESULTS: The CFTR was successful in all 20 attempts. The median resection time was 6 minutes (range 2.5-35 minutes). Suture closure was successful in 19 animals. It took a median time of 41 minutes (range 21-125 minutes) and 4 sutures to close the defect. Eighteen animals survived without clinical signs of distress; there was a well-healed scar without peritonitis or distant adhesions on necropsy at 2 weeks. One animal failed to thrive, and necropsy revealed mild peritonitis, small abscesses, distant adhesions, and a 2-mm hole at the suture site. Two of the 132 T-tags were inserted in the adjacent viscera. LIMITATIONS: Colon resection in the proximal colon was not studied. CONCLUSIONS: In this animal model, CFTR of the colon followed by suture closure can be accomplished successfully by using through-the-endoscope devices.
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3.56Impact points
Increased FGF-2 secretion and ability to support neurite outgrowth by astrocytes cultured on polyamide nanofibrillar matrices.
Matrix biology : journal of the International Society for Matrix Biology. 03/2009;
An electrospun nonwoven matrix of polyamide nanofibers was employed as a new model for the capillary basement membrane at the blood-brain barrier (BBB). The basement membrane separates astrocytes from endothelial cells and is associated with growth factors, such as fibroblast growth factor-2 (FGF-2)... [more] An electrospun nonwoven matrix of polyamide nanofibers was employed as a new model for the capillary basement membrane at the blood-brain barrier (BBB). The basement membrane separates astrocytes from endothelial cells and is associated with growth factors, such as fibroblast growth factor-2 (FGF-2). FGF-2 is produced by astrocytes and induces specialized functions in endothelial cells, but also has actions on astrocytes. To investigate potential autocrine actions of FGF-2 at the BBB, astrocytes were cultured on unmodified nanofibers or nanofibers covalently modified with FGF-2. The former assumed an in vivo-like stellate morphology that was enhanced in the presence of cross-linked FGF-2. Furthermore, astrocyte monolayers established on unmodified nanofibers were more permissive for neurite outgrowth when cultured with an overlay of neurons than similar monolayers established on standard tissue culture surfaces, while astrocytes cultured on FGF-2-modifed nanofibers were yet more permissive. The observed differences were due in part to progressively increasing amounts of FGF-2 secreted by the astrocytes into the medium; hence FGF-2 increases its own expression in astrocytes to modulate astrocyte-neuron interactions. Soluble FGF-2 was unable to replicate the effects of cross-linked FGF-2. Nanofibers alone up-regulated FGF-2, albeit to a lesser extent than nanofibers covalently modified with FGF-2. These results underscore the importance of both surface topography and growth factor presentation on cellular function. Moreover, these results indicate that FGF-2-modified nanofibrillar scaffolds may demonstrate utility in tissue engineering applications for replacement and regeneration of lost tissue following central nervous system (CNS) injury or disease.
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0.55Impact points
Frequency and magnitude of anxiety and depression in patients with psoriasis vulgaris.
Journal of the College of Physicians and Surgeons--Pakistan : JCPSP. 08/2008; 18(7):397-400.
OBJECTIVE: To determine the frequency of anxiety and depression in patients with psoriasis. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Outpatient Departments of Dermatology and Psychiatry, Ziauddin University Hospital, KDLB Campus, Karachi, from October 2005 to September 2006.... [more] OBJECTIVE: To determine the frequency of anxiety and depression in patients with psoriasis. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Outpatient Departments of Dermatology and Psychiatry, Ziauddin University Hospital, KDLB Campus, Karachi, from October 2005 to September 2006. PATIENTS AND METHODS: All patients presenting with psoriasis vulgaris above the age of 15 years, of either gender, fulfilling the selection criteria were included in the study. Clinical diagnosis was confirmed by biopsy and histopathology. Documentation of disease severity as mild, moderate and severe was done, using Psoriasis Area Severity Index (PASI). Patients were asked to fill "AKUADS" for their psychiatric assessment and scoring was done on this basis. Patients scoring equal to or above 19 were labeled as having anxiety or depression. RESULTS: There were 56 males (62%) and 33 females (38%), aged 20 to 65 years in the study. Out of those, 52 (58%) were married; while 37 (42%) were unmarried. The minimum duration of illness was 6 months and maximum 15 years. Thirty-four patients (38%) were suffering from mild disease, 31 (35%) from moderate and the remaining 24 (27%) from severe psoriasis. Twenty-four (27%) were on topical therapy while the other 65 (73%) were receiving systemic as well as topical therapy. Joint involvement was seen in 25 patients (28%) and nail changes in 31 (35%). Psychiatric illness was positive in 34 patients (38%, p<0.05) i.e. 20 males (59%) and 14 females (41%). Twenty-six patients (76%) were married (p<0.05). Anxiety and depression was seen irrespective of the disease duration. The mean "AKUADS" scores in accordance with disease severity were mild psoriasis 20, moderate psoriasis 22 and severe psoriasis 25. Twenty-one patients (62%, p=0.05) with joint involvement and another 23 (68%, p<0.05) with nail involvement had a score above 19. Thirty-one patients (91%) were receiving systemic as well as local therapy, while 3 patients (9%) were on topical treatment (p<0.05). CONCLUSION: There is an association of psoriasis vulgaris with anxiety and depression. The magnitude of this anxiety and depression can be influenced by variables of disease and life.
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6.71Impact points
Endoscopic closure of colon perforation compared to surgery in a porcine model: a randomized controlled trial (with videos).
Gastrointestinal endoscopy. 07/2008;
BACKGROUND: Endoscopic closure of inadvertent or intentional colon perforations might be valuable if comparable to surgical closure. OBJECTIVE: The aim of this study was to compare endoscopic closure of a 4-cm colon perforation in a porcine model with surgical closure in a multicenter study. SETTING... [more] BACKGROUND: Endoscopic closure of inadvertent or intentional colon perforations might be valuable if comparable to surgical closure. OBJECTIVE: The aim of this study was to compare endoscopic closure of a 4-cm colon perforation in a porcine model with surgical closure in a multicenter study. SETTING: University hospitals in the United States and Europe. DESIGN AND INTERVENTIONS: After creating a 4-cm linear colon perforation, the animals were randomized to either endoscopic or surgical closure. The total procedure time from the beginning of perforation to the completion of procedure was measured. The animals were euthanized after 2 weeks to evaluate healing, unless there was a complication. RESULTS: Fifty-four animals were randomized to either surgical or endoscopic closure of colon perforation. Eight animals developed complications, and 7 of these were euthanized before 2 weeks. Twenty-three animals in each group survived for 2 weeks. Surgical closure of the perforation was successful in all animals in that group, and endoscopic closure was successful in 25 of the 27 animals. The median procedure time was shorter in the surgery group compared to the endoscopy group (35 vs 44 minutes, P = .016). Peritonitis, local adhesions, and leak test results were comparable in both groups. Distant adhesions were less frequent in the endoscopic closure group (26.1% vs 56.5%, P = .03). Five of the 186 T-tags (2.7%) were noted in the adjacent viscera. LIMITATION: This porcine study does not mimic clean colon perforation in humans; it mimics dirty colon perforation in humans. CONCLUSIONS: Endoscopic closure of a 4-cm colon perforation was comparable to surgery, and this technique can be potentially used for closure of intentional or inadvertent colon perforations.
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1.90Impact points
Covalently attached FGF-2 to three-dimensional polyamide nanofibrillar surfaces demonstrates enhanced biological stability and activity.
Molecular and cellular biochemistry. 03/2008; 309(1-2):157-66.
Activation of fibroblast growth factor receptors (FGFRs) requires the formation of a ternary complex between fibroblast growth factors (FGFs), FGFRs, and heparan sulfate proteoglycans, which are all located on the cell surface and the basement membrane (BM)/extracellular matrix (ECM). Heparan sulfat... [more] Activation of fibroblast growth factor receptors (FGFRs) requires the formation of a ternary complex between fibroblast growth factors (FGFs), FGFRs, and heparan sulfate proteoglycans, which are all located on the cell surface and the basement membrane (BM)/extracellular matrix (ECM). Heparan sulfate proteoglycans appear to stabilize FGFs by inhibiting the rapid degradation of FGFs normally observed in solution. Because of the pivotal role of FGFs in proliferative and developmental pathways, a number of recent studies have attempted to engineer microenvironments to stabilize growth factors for use in applications in tissue culture and regenerative medicine. In this communication, we demonstrate that covalent linkage of FGF-2 to nanofibrillar surfaces (defined as covalently bound FGF-2) composed of a network of polyamide nanofibers resulted in the maintenance of the biological efficacy of FGF-2 when stored dry for at least 6 months at 25 degrees C or 4 degrees C. Moreover, covalently bound FGF-2 was more potent than FGF-2 in solution when measured in cellular assays of proliferation and viability using a variety of cell types. Covalently bound FGF-2 also strongly activated FGFR, extracellular signal-regulated kinase (ERK1/2), and c-fos. Hence cell-signaling molecules can be incorporated into a synthetic nanofibrillar surface, providing a novel means to enhance their stability and biological activity.
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0.55Impact points
Alopecia areata in children.
Journal of the College of Physicians and Surgeons--Pakistan : JCPSP. 10/2007; 17(10):587-90.
Objective: To determine the clinical presentations of alopecia areata in children as well as the frequency of associated disorders. Design: Cross-sectional study. Place and Duration of Study: Department of Dermatology, Ziauddin University Hospital, KDLB Campus, Karachi during the calendar years 2005... [more] Objective: To determine the clinical presentations of alopecia areata in children as well as the frequency of associated disorders. Design: Cross-sectional study. Place and Duration of Study: Department of Dermatology, Ziauddin University Hospital, KDLB Campus, Karachi during the calendar years 2005 and 2006. Patients and Methods: Children of either gender suffering from alopecia areata, upto 15 years of age, who fulfilled the selection criteria were included in the study. Only freshly registered cases were studied. Severity of the disease was graded as mild, moderate and severe disease, and other clinical patterns including alopecia totalis, alopecia universalis and ophiasis. Hematological and biochemical profile was evaluated. Chi-square test was applied for statistical analysis in order to determine p-value using the percentages of variables. Results: One hundred and fourteen patients comprising 54 males (47%) and 60 females (53%), aged 4 upto 15 years, the mean age being 9.1 years, were enrolled. Family history of alopecia areata was positive in 11 patients (10%). Fifty nine patients (51%) were of age 6-10 years, 39 patients (35%), aged 11-15 years, and 16 (14%) were of age below 5 years. Mild alopecia areata (41%, p < 0.05) was the most common presentation followed by moderate disease (31%, p < 0.05), severe alopecia (17%, p < 0.05), alopecia totalis (7%, p < 0.05), alopecia universalis (2.7%, p=0.05) and ophiasis (1.7%, p=0.05). Nail changes were found in 40 patients (35%, p < 0.05). Definite evidence of atopy was obtained in 23 patients (20%, p< 0.05). The autoimmune disorders associated with alopecia areata included: hypothyroidism (4.3%), vitiligo (3.5%), psoriasis (1.8%), systemic lupus erythematosus (SLE 0.9%), hypoparathyroidism (0.9%) and diabetes mellitus (0.9%). Conclusion: The spectrum of childhood alopecia areata ranges from mild, moderate and severe alopecia, ultimately to alopecia totalis, alopecia universalis and ophiasis. Nail changes as well as atopy and autoimmune disorders are the associated disorders.
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Frequency of raised serum IgE level in childhood atopic dermatitis.
JPMA. The Journal of the Pakistan Medical Association. 10/2007; 57(9):431-4.
OBJECTIVE: To see the frequency of raised serum IgE level in children with atopic dermatitis. METHODS: The study was conducted in the out patient department of Dermatology, "Ziauddin University", KDLB Campus Karachi, from 1st October 2005, till 30th September 2006. Patients belonging to bo... [more] OBJECTIVE: To see the frequency of raised serum IgE level in children with atopic dermatitis. METHODS: The study was conducted in the out patient department of Dermatology, "Ziauddin University", KDLB Campus Karachi, from 1st October 2005, till 30th September 2006. Patients belonging to both sexes, aged upto 15 years, clinically diagnosed as atopic dermatitis were enrolled. The clinical severity was graded as mild, moderate and severe forms. Sera of all these patients were tested for IgE levels by ELISA. RESULTS: The study comprised of 124 patients, including 73 males (59%) and 51 females (41%). A total of 86 patients (70%) had a raised serum IgE level from a cut off value of 87 IU/ml. A large number of patients suffered from moderate disease (47%), followed by mild form (33%) and severe disease (20%). Serum IgE levels were divided into 3 groups i.e. upto cut off value (87 IU/ml) accounting for 31%, followed by 88 to 1000 IU/ml (41%) and 1001 to 3000 IU/ml (28%). Of the severely affected 25 patients (20%), 20 (57%) had values ranging from 1001 to 3000 IU/ml while another 3 (6%) ranged less then 1000 IU/ml (P < 0.001). Of those with moderate disease (47%), 13 patients (37%) had serum IgE levels ranging from 1001 to 3000 IU/ml, while 25 (49%) had levels less then 1000 IU/ml (P = 0.24). Of those affected mildly (33%), 23 (45%) had values ranging from 88 upto 1000 IU/ml and 2 patients (6%) had levels from 1001 to 3000 IU/ml (P < 0.001). CONCLUSION: Majority of children suffering from atopic dermatitis have a raised serum level of IgE, which in turn correlates well with severity of the disease.
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1.90Impact points
Morphology, cytoskeletal organization, and myosin dynamics of mouse embryonic fibroblasts cultured on nanofibrillar surfaces.
Molecular and cellular biochemistry. 08/2007; 301(1-2):241-9.
Growth of cells in tissue culture is generally performed on two-dimensional (2D) surfaces composed of polystyrene or glass. Recent work, however, has shown that such 2D cultures are incomplete and do not adequately represent the physical characteristics of native extracellular matrix (ECM)/basement ... [more] Growth of cells in tissue culture is generally performed on two-dimensional (2D) surfaces composed of polystyrene or glass. Recent work, however, has shown that such 2D cultures are incomplete and do not adequately represent the physical characteristics of native extracellular matrix (ECM)/basement membrane (BM), namely dimensionality, compliance, fibrillarity, and porosity. In the current study, a three-dimensional (3D) nanofibrillar surface composed of electrospun polyamide nanofibers was utilized to mimic the topology and physical structure of ECM/BM. Additional chemical cues were incorporated into the nanofibrillar matrix by coating the surfaces with fibronectin, collagen I, or laminin-1. Results from the current study show an enhanced response of primary mouse embryonic fibroblasts (MEFs) to culture on nanofibrillar surfaces with more dramatic changes in cell spreading and reorganization of the cytoskeleton than previously observed for established cell lines. In addition, the cells cultured on nanofibrillar and 2D surfaces exhibited differential responses to the specific ECM/BM coatings. The localization and activity of myosin II-B for MEFs cultured on nanofibers was also compared. A dynamic redistribution of myosin II-B was observed within membrane protrusions. This was previously described for cells associated with nanofibers composed of collagen I but not for cells attached to 2D surfaces coated with monomeric collagen. These results provide further evidence that nanofibrillar surfaces offer a significantly different environment for cells than 2D substrates.
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2.46Impact points
Role of DNA topoisomerase IIbeta in neurite outgrowth.
Brain research. 07/2007; 1154:50-60.
Failure to establish neuromuscular junctions is a major phenotype of top2beta knockout mice. However, the precise mechanism for this defect is not known. In the current study, we have investigated the role of TopIIbeta in cultured neurons. We showed that the TopII inhibitor ICRF-193 significantly bl... [more] Failure to establish neuromuscular junctions is a major phenotype of top2beta knockout mice. However, the precise mechanism for this defect is not known. In the current study, we have investigated the role of TopIIbeta in cultured neurons. We showed that the TopII inhibitor ICRF-193 significantly blocked neurite outgrowth and growth cone formation in cultured cerebellar granule neurons (CGNs), dorsal root ganglions (DRGs) and cortical neurons (CNs). In addition, ICRF-193 also blocked neurite outgrowth and growth cone formation of PC12 cells undergoing NGF-induced differentiation. Isolated cortical neurons from top2beta knockout embryos elaborated shorter neurites than did those from their wild type counterparts, confirming the role of TopIIbeta in neurite outgrowth. Together, these results demonstrate a critical role of TopIIbeta in neurite outgrowth in cultured neurons. Furthermore, we demonstrated that neurons derived from top2beta knockout mice failed to form contacts with muscle cells in co-cultures. These results suggest that the defect in establishing neuromuscular junctions in top2beta knockout mice could be due to the lack of TopIIbeta-mediated neurite outgrowth.
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6.71Impact points
Endoluminal suturing may overcome the limitations of clip closure of a gaping wide colon perforation (with videos).
Gastrointestinal endoscopy. 06/2007; 65(6):906-11.
BACKGROUND: It is unclear whether large gaping perforations of the colon can be closed by the endoluminal route. OBJECTIVE: To evaluate the feasibility and the outcome of closure of large perforations of colon with clips and sutures by using through-the-endoscope novel devices. DESIGN: Prospective a... [more] BACKGROUND: It is unclear whether large gaping perforations of the colon can be closed by the endoluminal route. OBJECTIVE: To evaluate the feasibility and the outcome of closure of large perforations of colon with clips and sutures by using through-the-endoscope novel devices. DESIGN: Prospective animal study. SETTING: University hospital. PATIENTS: Ten pigs. INTERVENTIONS: Closure of a 4-cm full-thickness colon perforation freshly created by an insulated-tip knife with the InScope Multi-Clip Applier (n = 6) and with the tissue approximation device (n = 4). MAIN OUTCOME MEASUREMENTS: (a) Technical feasibility of closure, (b) clinical monitoring for 2 weeks, (c) necropsy (day 14), (d) healing by a dye-leak test and histology. RESULTS: Endoluminal closure of a 4-cm-long colon perforation was successful in 9 of 10 animals. The clips failed to close a gaping wide colon perforation in 1 animal. The sutures were successful in the closure of both nongaping and gaping perforations. Successful closure resulted in a leakproof sealing at 2 weeks and prevented clinical peritonitis in all the animals in the clip-closure group and in 3 of 4 animals in the suture-closure group. Necropsy at 2 weeks revealed mild peritonitis in 2 of the 5 animals in the clip closure group and in 2 of the 4 animals in the suture-closure group; none developed fecal peritonitis. LIMITATIONS: None. CONCLUSIONS: Endoluminal closure of a 4-cm colon perforation with clips was successful in the majority of cases. Sutures were useful in the closure of gaping colon perforations that could not be closed with clips.
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6.71Impact points
Study of full-thickness endoluminal segmental resection of colon in a porcine colon model (with videos).
Gastrointestinal endoscopy. 05/2007; 65(4):696-702.
BACKGROUND: Entrapment injury of the adjacent bowel is frequently encountered during full-thickness endoluminal colon suction-resection. OBJECTIVE: Our purpose was to develop a technique that can create a full-thickness resection of the colon without the risk of entrapment injury to adjacent viscera... [more] BACKGROUND: Entrapment injury of the adjacent bowel is frequently encountered during full-thickness endoluminal colon suction-resection. OBJECTIVE: Our purpose was to develop a technique that can create a full-thickness resection of the colon without the risk of entrapment injury to adjacent viscera. DESIGN: Pilot study. SETTING: University medical center. PATIENTS: Five pigs. INTERVENTIONS: Traction-resection of the colon was created by using a grasping forceps to pull the colon into a band ligator loaded on a double-channel endoscope, followed by the application of a band, and subsequent snare resection (n = 14). Suction-resection of the colon was created by using a double-channel endoscope loaded with a band ligator (n = 12) and a single-channel endoscope with a band ligator (n = 6). MAIN OUTCOME MEASUREMENTS: Number of full-thickness colon resections, frequency of the adjacent bowel and mesenteric injury, and the size of the resections were measured. RESULTS: The suction-resection technique resulted in significant injury to adjacent viscera compared with the traction-resection technique (56% vs 0%, P = .0013). The traction-resection method resulted in a significantly larger resection compared with the suction-resection method (mean +/- SEM: 2.91 +/- 0.3 cm vs 2.1 +/- 0.1 cm, P = .024). A double-channel endoscope suction-resection method resulted in a significantly larger resection compared with a single channel suction-resection technique (mean +/- SEM: 2.1 +/- 0.1 cm vs 0.91 +/- 0.2 cm, P = .0022). LIMITATIONS: None. CONCLUSIONS: The traction-resection technique is safer than the suction-resection method in removing larger specimens of the colon. In addition, the traction-resection technique reduces the risk of injury of the mesentery or adjacent small intestine.
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6.71Impact points
Endoluminal clip closure of a circular full-thickness colon resection in a porcine model (with videos).
Gastrointestinal endoscopy. 04/2007; 65(3):503-9.
BACKGROUND: Linear perforations of the colon can be closed by the application of clips through a colonoscope. It is unclear whether circular perforations after full-thickness resection of the colon can be closed with clips. OBJECTIVE: To develop an animal model for circular perforation of the colon ... [more] BACKGROUND: Linear perforations of the colon can be closed by the application of clips through a colonoscope. It is unclear whether circular perforations after full-thickness resection of the colon can be closed with clips. OBJECTIVE: To develop an animal model for circular perforation of the colon and to study different techniques to accomplish a leakproof sealing of the circular perforation of the colon. DESIGN: Pilot study. SETTING: University medical center. ANIMALS: Ten pigs: 2 perforations in the 1st pig and 1 perforation in the 2nd to 9th pigs were closed with clips. In the 10th pig, 5 perforations were created, and the dimensions of the perforation were measured. INTERVENTIONS: Creation of a circular full-thickness resection of the colon with a band-ligation-resection device, followed by longitudinal or transverse endoluminal closure of the perforation by using the first clip opened and applied in the 3- to 9-o'clock or the 6- to 12-o'clock direction in relation to the circular perforation, respectively. MAIN OUTCOME MEASUREMENTS: The mean (standard deviation) size of circular perforation was 1.7 +/- 0.075 cm (range, 1.5-2.0 cm). Necropsy immediately after closure of the perforation was done to examine the closure and to confirm the quality of sealing with the methylene blue dye leak test. RESULTS: The transverse closure was unsuccessful in the closure of 3 perforations, whereas the longitudinal closure resulted in a leakproof sealing in 6 of the 7 closures. LIMITATIONS: Perforation of the adjacent viscera limits it to a nonsurvival study. CONCLUSIONS: Endoluminal application of clips by using the longitudinal closure technique results in a leak proof sealing of circular perforations of the colon.
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6.71Impact points
Controlled trial of immediate endoluminal closure of colon perforations in a porcine model by use of a novel clip device (with videos).
Gastrointestinal endoscopy. 01/2007; 64(6):989-97.
BACKGROUND: Although endoluminal closure of a small perforation of the colon is technically feasible, the outcome of such a closure is unclear. OBJECTIVE: Our purpose was to evaluate the feasibility and the outcome of endoluminal closure of a small perforation of the colon with a novel clip device, ... [more] BACKGROUND: Although endoluminal closure of a small perforation of the colon is technically feasible, the outcome of such a closure is unclear. OBJECTIVE: Our purpose was to evaluate the feasibility and the outcome of endoluminal closure of a small perforation of the colon with a novel clip device, the InScope MultiClip Applier (IMCA), and to assess the number of clips required for successful closure. DESIGN: Prospective controlled study. SETTING: University hospital. ANIMALS: 17 pigs. INTERVENTIONS: A 2-cm full-thickness colon perforation was randomized to 3 groups: control, no closure (n = 4), 2-clip closure (n = 7), and 4-clip closure (n = 6). MAIN OUTCOME MEASUREMENTS: (1) Technical feasibility of closure, (2) closure time, (3) clinical monitoring for 2 weeks, (4) necropsy (day 14), and (5) healing by a dye leak test and histologic examination. RESULTS: Endoscopic closure of the colon perforation was technically successful in 12 of 13 animals. A wide gaping hole prevented satisfactory closure in 1 animal. The median time for closure with 2 and 4 clips was 2 and 3 minutes, respectively. Clip closure of perforation prevented clinical sepsis (P = .008) and diminished the risk for fibrinous peritonitis (P = .02 for a single test of hypothesis; however, correction for the multiple testing of data removes this significance) and adhesion formation (P = .008) compared with controls, without any leakage. The outcomes of 2- and 4-clip closure were similar. CONCLUSIONS: Endoluminal closure of a 2-cm colon perforation with clips is successful in preventing peritonitis and adhesions and it can be accomplished quickly with this novel device. Clip closure at 1-cm intervals is sufficient for successful closure of a 2-cm colon perforation.
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6.71Impact points
Endoluminal closure of large perforations of colon with clips in a porcine model (with video).
Gastrointestinal endoscopy. 11/2006; 64(4):640-6.
BACKGROUND: Endoluminal clip closure of small perforations of the colon is possible. It is unclear whether large perforations of the colon can be closed with clips deployed through a colonoscope. OBJECTIVES: To evaluate the technical feasibility and outcome of endoluminal closure of large perforatio... [more] BACKGROUND: Endoluminal clip closure of small perforations of the colon is possible. It is unclear whether large perforations of the colon can be closed with clips deployed through a colonoscope. OBJECTIVES: To evaluate the technical feasibility and outcome of endoluminal closure of large perforations of the colon with clips. DESIGN: Pilot study. SUBJECTS: Eight pigs. INTERVENTIONS: Endoluminal clip closure of large perforations of the colon. MAIN OUTCOME MEASUREMENTS: Technical feasibility of endoluminal closure was evaluated in 8 animals. A dye leak test was performed to evaluate quality of endoluminal sealing immediately after closure and 2 weeks after closure. The animals in the survival group were monitored daily for 2 weeks for sepsis and peritonitis. Necropsy was done on day 14 to check for fecal peritonitis, wound dehiscence, and histological healing of perforation. RESULTS: Endoscopic closure of colon perforation was successful in 6 of 8 animals; in 2 animals closure was unsuccessful due to prolapse of adjacent viscera into the colon (n = 1) and severe bleeding that obscured the view (n = 1). There was a leak-proof sealing of the perforation site in 2 animals tested immediately and in all the animals tested (n = 3) 2 weeks after closure. All 4 animals in the survival group recovered well, without any sepsis or peritonitis. Necropsy did not reveal fecal peritonitis or pericolonic abscess formation. The perforation site demonstrated a thin scar and there was histological healing. CONCLUSIONS: Endoluminal application of clips is successful in the closure of a large perforation of the colon in a porcine model.
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6.71Impact points
Immediate endoscopic closure of colon perforation by using a prototype endoscopic suturing device: feasibility and outcome in a porcine model (with video).
Gastrointestinal endoscopy. 08/2006; 64(1):113-9.
BACKGROUND: Perforation is an uncommon but potentially devastating complication of colonoscopy. Surgical closure is the standard of care. Immediate endoluminal closure of a perforation would avoid the morbidity and mortality associated with general anesthesia, laparotomy, and surgical repair. OBJECT... [more] BACKGROUND: Perforation is an uncommon but potentially devastating complication of colonoscopy. Surgical closure is the standard of care. Immediate endoluminal closure of a perforation would avoid the morbidity and mortality associated with general anesthesia, laparotomy, and surgical repair. OBJECTIVES: To evaluate the feasibility and safety of full-thickness endoscopic closure of colonic perforations with a prototype endoscopic suturing device, the Eagle Claw, in a porcine model. DESIGN: Endoscopic animal experimental study of closure of colon perforation by using a porcine model. SUBJECTS: Ten pigs were included in the study. INTERVENTIONS: The Eagle Claw was used to close small perforations (1.5 to 2 cm) of the colon created by needle-knife with the animal under general anesthesia by using the endoluminal route. All animals received intravenous antibiotics and were allowed to eat after 24 hours. MAIN OUTCOME MEASUREMENTS: The animals were monitored daily for signs of sepsis and peritonitis. On day 7, they were euthanized. The peritoneal cavity was examined for fecal peritonitis, and the colon perforation site was checked for wound dehiscence and pericolic abscess formation. RESULTS: Endoscopic closure of the colon perforation was successful in 7 animals, and they recovered well without any sepsis or peritonitis. Necropsy did not reveal fecal peritonitis or pericolonic abscess formation at the site of perforation, and the perforation healed well. Closure was successful in 1 animal, but necropsy revealed dehiscence of the colon perforation site. Endoscopic closure was unsuccessful in 2 animals, and these were euthanized immediately. CONCLUSIONS: Closure of acute perforation of the colon is feasible with the Eagle Claw endoscopic suturing device in a porcine model.
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2.82Impact points
Three-dimensional nanofibrillar surfaces covalently modified with tenascin-C-derived peptides enhance neuronal growth in vitro.
Journal of biomedical materials research. Part A. 04/2006; 76(4):851-60.
Current methods to promote growth of cultured neurons use two-dimensional (2D) glass or polystyrene surfaces coated with a charged molecule (e.g. poly-L-lysine (PLL)) or an isolated extracellular matrix (ECM) protein (e.g. laminin-1). However, these 2D surfaces represent a poor topological approxima... [more] Current methods to promote growth of cultured neurons use two-dimensional (2D) glass or polystyrene surfaces coated with a charged molecule (e.g. poly-L-lysine (PLL)) or an isolated extracellular matrix (ECM) protein (e.g. laminin-1). However, these 2D surfaces represent a poor topological approximation of the three-dimensional (3D) architecture of the assembled ECM that regulates neuronal growth in vivo. Here we report on the development of a new 3D synthetic nanofibrillar surface for the culture of neurons. This nanofibrillar surface is composed of polyamide nanofibers whose organization mimics the porosity and geometry of the ECM. Neuronal adhesion and neurite outgrowth from cerebellar granule, cerebral cortical, hippocampal, motor, and dorsal root ganglion neurons were similar on nanofibers and PLL-coated glass coverslips; however, neurite generation was increased. Moreover, covalent modification of the nanofibers with neuroactive peptides derived from human tenascin-C significantly enhanced the ability of the nanofibers to facilitate neuronal attachment, neurite generation, and neurite extension in vitro. Hence the 3D nanofibrillar surface provides a physically and chemically stabile cell culture surface for neurons and, potentially, an exciting new opportunity for the development of peptide-modified matrices for use in strategies designed to encourage axonal regrowth following central nervous system injury.
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7.75Impact points
Three-dimensional nanofibrillar surfaces promote self-renewal in mouse embryonic stem cells.
Stem cells (Dayton, Ohio). 03/2006; 24(2):426-33.
The regulation of mouse embryonic stem cell (mESC) fate is controlled by the interplay of signaling networks that either promote self-renewal or induce differentiation. Leukemia inhibitory factor (LIF) is a cytokine that is required for stem cell renewal in mouse but not in human embryonic stem cell... [more] The regulation of mouse embryonic stem cell (mESC) fate is controlled by the interplay of signaling networks that either promote self-renewal or induce differentiation. Leukemia inhibitory factor (LIF) is a cytokine that is required for stem cell renewal in mouse but not in human embryonic stem cells. However, feeder layers of embryonic fibroblasts are capable of inducing stem cell renewal in both cell types, suggesting that the self-renewal signaling pathways may also be promoted by other triggers, such as alternative cytokines and/or chemical or physical properties of the extracellular matrix (ECM) secreted by feeder fibroblasts. We have recently used a synthetic polyamide matrix (Ultra-Web) whose three-dimensional (3D) nanofibrillar organization resembles the ECM/basement membrane. Growth of mESCs on this nanofibrillar surface greatly enhanced proliferation and self-renewal in comparison with growth on tissue culture surfaces without nanofibers, despite the presence of LIF in both systems. Enhanced proliferation and self-renewal of the stem cells on nanofibrillar surfaces were correlated with the activation of the small GTPase Rac, the activation of phosphoinositide 3-kinase (PI3K) pathway, and the enhanced expression of Nanog, a homeoprotein required for maintenance of pluripotency. Inhibitors of PI3K reduced the expression level of Nanog in mESCs cultured on 3D nanofibrillar surfaces. These results provide support for the view that the three-dimensionality of the culture surface may function as a cue for the activation of Rac and PI3K signaling pathways, resulting in stem cell proliferation and self-renewal.
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2.41Impact points
Ultra-structural morphological abnormalities of the urinary bladder in streptozotocin-induced diabetic female rats.
International urogynecology journal and pelvic floor dysfunction. 03/2006; 17(2):143-54.
The objective of this study was to evaluate the ultra-structural changes in the urinary bladder of diabetic rats in relation to disease duration since the morphological bases of diabetes-induced bladder dysfunction are poorly understood. Urinary bladders were examined chronologically by electron mic... [more] The objective of this study was to evaluate the ultra-structural changes in the urinary bladder of diabetic rats in relation to disease duration since the morphological bases of diabetes-induced bladder dysfunction are poorly understood. Urinary bladders were examined chronologically by electron microscopy in a female Wistar-rat model of streptozotocin-induced diabetes mellitus and compared to control samples. Numerous dark mitochondria with swollen cristae and electron lucent, large, calcified and degenerated mitochondria were observed first in the urothelium. Intraepithelial capillaries surrounded by thick collagen were also present. Gap junctions between myocytes were interrupted or extensively widened with reduced mitochondria and caveolae. Collagen accumulation, degenerated nerve fibres and myelin bodies were seen between myocytes with increased collagen content and frequent mast cells, phagocytes and lymphocyte aggregates in the stroma. All ultra-structural lesions became augmented with longer duration of diabetes. Diabetes induces time-dependent pathologic changes in the urinary bladder of rats that might account for bladder dysfunction.
Following (1)
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Rizwan Ishaq
Universidad de Deusto
Topics (1)
