Exploring the cytotoxic potential of biflavones of Araucaria cunninghamii: Precise identification combined by LC-HRMS-metabolomics and database mining, targeted isolation, network pharmacology, in vitro cytotoxicity, and docking studies.

The leaves of Araucaria cunninghamii are known to be nonedible and toxic. Previous studies have identified biflavones in various Araucaria species. This study aimed to investigate the in vitro cytotoxicity of the isolated compounds from Araucaria cunninghamii after metabolomics and network pharmacological analysis. Methanol extract of Araucaria cunninghamii leaves was subjected to bioassay-guided fractionation. The active fraction was analyzed using LC-HRMS, through strategic database mining, by comparing the data to the Dictionary of Natural Products to identify 12 biflavones, along with abietic acid, beta-sitosterol, and phthalate. Eight compounds were screened for network pharmacology study, where in silico ADME analysis, prediction of gene targets, compound-gene-pathway network and hierarchical network analysis, protein-protein interaction, KEGG pathway, and Gene Ontology analyses were done, that showed PI3KR1, EGFR, GSK3B, and ABCB1 as the common targets for all the compounds that may act in the gastric cancer pathway. Simultaneously, four biflavones were isolated via chromatography and identified through NMR as dimeric apigenin with varying methoxy substitutions. Cytotoxicity study against the AGS cell line for gastric cancer showed that AC1 biflavone (IC50 90.58 µM) exhibits the highest cytotoxicity and monomeric apigenin (IC50 174.5 µM) the lowest. Besides, the biflavones were docked to the previously identified targets to analyze their binding affinities, and all the ligands were found to bind with energy ≤-7 Kcal/mol.

National Cancer Registry of Pakistan: First Comprehensive Report of Cancer Statistics 2015-2019.

OBJECTIVE: To compile a comprehensive national cancer registry report of Pakistan by merging and analysing cancer registration data received from major functional cancer registries in various parts of Pakistan. STUDY DESIGN: Observational study. Place and Duration of the Study: Health Research Institute (HRI), National Institutes of Health (NIH), Islamabad, from 2015-2019. METHODOLOGY: Data from major cancer registries which included 'Punjab Cancer Registry (PCR), 'Karachi Cancer Registry (KCR)', 'Pakistan Atomic Energy Commission (PAEC) Cancer Registry', Armed Forces Institute of Pathology (AFIP) Cancer Registry, Nishtar Medical University Hospital Multan (NMH), and Shifa International Hospital, Islamabad (SIH) registries were pooled, cleared, and analysed at HRI. RESULTS: A total of 269,707 cancer cases were analysed. Gender-wise 46.7% were males and 53.61% were females. As per province-wise distribution, 45.13% of cases were from Punjab, 26.83% from Sindh, 16.46% from Khyber Pakhtunkhwa (KP), and 3.52% from Baluchistan. Both genders combined, 'breast cancer' 57633 (21.4%) was the most common cancer. In males, the top-5 cancers in order of frequency/percenatages were 'oral' 14477 (11.6%), 'liver' 8398 (6.73%), colorectal 8024 (6.43%), 'lung' 7547 (6.05%) and 'prostate' 7322 (5.87% cancers). In females, causes of the top-5-cancers included 'breast' 56250 (38.8%), 'ovary' 8823 (6.09%), 'oral' 7195 (4.97%), 'cervix' 6043 (4.17%), and 'colorectal' 4860 (3.36%) cancers. In children 'Leukemia' 1626 (14.50%) and in adolescents 'Bone' 880 (14%) were the leading malignancies. CONCLUSION: Breast cancer is the most common cancer in females touching epidemic proportions while 'oral cancer' which is the leading cancer in males ranks third in frequency in females. Like 'oral cancer' which shows a strong correlation with chewing, other common cancers in Pakistan including liver cancer, lung cancer, and cervical cancer are also largely preventable as showed a strong correlation with hepatitis B and C, smoking, and high-risk human papillomavirus. KEY WORDS: National Cancer Registry, Health Research Institute - NIH, Islamabad, Pakistan.

Comparison of coronary revascularization strategies in older adults presenting with acute coronary syndromes.

BACKGROUND: The optimal coronary revascularization strategy to maximize the patient-centered outcome of days alive and out of hospital (DAOH), in multimorbid older (≥65-years) adults after an acute coronary syndrome (ACS) is incompletely understood. METHODS: Using Kaiser Permanente Northern California Health Plan databases, we identified 3871 patients ≥65-years presenting with ACS between 1/1/2010-3/1/2018 who underwent coronary revascularization with either coronary artery bypass grafting (CABG, N = 1575) or multivessel percutaneous coronary intervention (PCI, N = 2296). Selection bias was accounted for through propensity score modeling techniques and inverse probability of treatment weighting. Cox proportional hazards models were fit to evaluate the association of revascularization type with outcomes. PRIMARY OUTCOMES: Absolute DAOH and the relative risk of achieving ≥90%DAOH during three time intervals. SECONDARY OUTCOMES: All-cause mortality, recurrent MI, stroke, rehospitalization, repeat revascularization, and dialysis initiation. RESULTS: CABG (compared to PCI) was associated with greater absolute number of DAOH, significant after the first year (mean difference at 1-year: +5.8 days, 95% confidence interval [CI], -1.6 to 13 days; 3-years: +56 days, 95%CI, +25 to +88 days; 5-years: + 131 days, 95%CI, +57 to +205 days). The relative risk of achieving ≥90% DAOH significantly favored CABG after the first year (1-year:1.02, 95%CI, 0.98-1.05; 3-years:1.06, 95%CI 1.002-1.11, 5-years:1.12, 95%CI, 1.03-1.22), and was related to lower incidences of all-cause mortality, repeat revascularization, rehospitalization, incident dialysis, and nonfatal MI with CABG. CONCLUSIONS: In older adults with multivessel or left main coronary artery disease who presented with ACS, CABG, after the first year, was associated with a greater absolute number of DAOH-a geriatric and patient-centered outcome, compared to PCI. CABG patients also had a higher probability of achieving ≥90%DAOH-with lower all-cause mortality, recurrent MI, repeat revascularization, new dialysis, and rehospitalization rates. Future randomized trials should study the impact of optimal revascularization strategies on the quality of life of older adults with multimorbidity.

Diagnosis and Management of Diffuse Large B-Cell Lymphoma: Society of Medical Oncology, Pakistan Society of Hematology, and Pakistan Society of Clinical Oncology Joint Clinical Practice Guideline.

Diffuse large B-cell lymphoma (DLBCL) is the commonest non-Hodgkin lymphoma encountered by hematopathologists and oncologists. Management guidelines for DLBCL are developed and published by countries with high income and do not cater for practical challenges faced in resource-constrained settings. This report by a multidisciplinary panel of experts from Pakistan is on behalf of three major national cancer societies: Society of Medical Oncology Pakistan, Pakistan Society of Hematology, and Pakistan Society of Clinical Oncology. The aim is to develop a practical and standardized guideline for managing DLBCL in Pakistan, keeping in view local challenges, which are similar across most of the low- and middle-income countries across the globe. Modified Delphi methodology was used to develop consensus guidelines. Guidelines questions were drafted, and meetings were convened by a steering committee to develop initial recommendations on the basis of local challenges and review of the literature. A consensus panel reviewed the initial draft recommendations and rated the guidelines on a five-point Likert scale; recommendations achieving more than 75% consensus were accepted. Resource grouping initially suggested by Breast Health Global Initiative was applied for resource stratification into basic, limited, and enhanced resource settings. The panel generated consensus ratings for 35 questions of interest and concluded that diagnosis and treatment recommendations in resource-constrained settings need to be based on available resources and management expertise.

Screening of phytochemical constituents and potential antioxidant, antibacterial and anticancerous activities of Carpesium nepalense seeds oil.

The pharmacological importance and ecofriendly nature of medicinal plants holding a unique edge in the arena of pharmaceutical industries. Therefore, the current research was aimed to evaluate the phytochemical constituents and potential antioxidant, in vitro anticancer and antibacterial activity of Carpesium nepalense seeds essential oil. The analysis performed through Gas chromatography/Mass spectroscopy confirmed the presence of different types of biologically active compounds. At the concentration of 500µg/mL, n-hexane fraction of C. nepalense showed highly significant (P<0.001) antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid and superoxide assays with the percentage inhibitions of 86.60±1.6%, 82.55±1.0% and 80.50±1.0% respectively. The extract also produced highly significant anticancerous activity against different cell lines at 500µg/mL. The significant antibacterial activity of extract was observed against bacterial strains with the zone of inhibitions of 24.3±0.8, 28.20±0.10, 22.33±0.11 and 33.22±0.10 mm respectively. The significant damage in bacterial cell membranes was also observed in atomic force microscopic analysis. In the light of obtained findings, it is concluded that C. nepalence proved to be a potential candidate as an alternative medicinal agent.

Synthesis and characterization of Schiff base of nicotinic hydrazide as antibacterial agent along with in vivo wound healing activities and atomic force microscopic study of bacterial cell wall affected by synthesized compound.

The present work reports the synthesis of Schiff base series of nicotinic hydrazide (C-1-C-5) and it's antibacterial and wound healing evaluation. The synthetic molecules were characterized with different spectroscopic techniques and explored for their antibacterial potential. The objective of this work was to explore antimicrobial agent using two types of microorganisms, one Gram-positive (S. aureus ATCC 9144) and one Gram-negative (E. coli ATCC 10536). C-2, C-4 and C-5 potentially inhibit bacterial growth (p<0.001). Atomic force microscopy (AFM) imaging was obtained to get high-resolution images of the effect of treated drugs on the bacterial morphology. The images obtained also revealed the antibacterial effects of potent molecule. The magnified pictures captured under AFM suggest significantly damaged cell surface and disturbed morphology. The compounds were further analyzed for in vivo wound healing potential on mice. The compound C-2, C-4 and C-5 heal the wounds comparatively in less time duration as compared to control group (p<0.001). Compound C-1 and C-3 took more time to heal the wound as compare to compound C-2, C-4 and C-5. The re-epithelialization process of wound in animals group treated with potent compound was highly significant (p<0.001) and faster than control. Results of this study suggest that the compounds C-2, C-4 andC-5 possess pronounced antibacterial and wound healing potential and need to be further evaluated for mechanism of action.

Caffeine inhibits hypoxia-induced nuclear accumulation in HIF-1α and promotes neonatal neuronal survival.

Apnea of prematurity (AOP) defined as cessation of breathing for 15-20 s, is commonly seen in preterm infants. Caffeine is widely used to treat AOP due to its safety and effectiveness. Caffeine releases respiratory arrest by competing with adenosine for binding to adenosine A1 and A2A receptors (A1R and A2AR). Long before its use in treating AOP, caffeine has been used as a psychostimulant in adult brains. However, the effect of caffeine on developing brains remains unclear. We found that A1R proteins for caffeine binding were expressed in the brains of neonatal rodents and preterm infants (26-27 weeks). Neonatal A1R proteins colocalized with PSD-95, suggesting its synaptic localization. In contrast, our finding on A2R expression in neonatal neurons was restricted to the mRNA level as detected by single cell RT/PCR due to the lack of specific A2AR antibody. Furthermore, caffeine (200 µM) at a dose twice higher than the clinically relevant dose (36-130 µM) had minor or no effects on several basic neuronal functions, such as neurite outgrowth, synapse formation, expression of A1R and transcription of CREB-1 and c-Fos, further supporting the safety of caffeine for clinical use. We found that treatment with CoCl2 (125 µM), a hypoxia mimetic agent, for 24 h triggered neuronal death and nuclear accumulation of HIF-1α in primary neuronal cultures. Subsequent treatment with caffeine at a concentration of 100 µM alleviated CoCl2-induced cell death and prevented nuclear accumulation of HIF-1α. Consistently, caffeine treatment in early postnatal life of neonatal mice (P4-P7) also prevented subsequent hypoxia-induced nuclear increase of HIF-1α. Together, our data support the utility of caffeine in alleviating hypoxia-induced damages in developing neurons.

Differentiation of beta thalassemia trait from iron deficiency anemia by hematological indices.

OBJECTIVE: We aimed at finding out reliable parameter in the differentiation of iron deficiency anemia (IDA) and beta-thalassemia trait (ß-TT) in the adult population subjected to Saudi Arabian Premarital Screening Program. METHODS: A total of 620 adults (age range 21-36 years) reported during February 2012 to November 2012. Tests for serum iron and ferritin were carried out in individuals showing low hemoglobin (Hb). All the selected subjects' samples were subjected to blood morphology, comparison of MCV, RBC count. Red Cell Distribution Width (RDW) was noted from the Coulter Report whereas Red Cell Distribution Width Index (RDWI) value was calculated for all the samples. RESULTS: A total of one hundred &thirty-five individuals with hypochromic microcytic anemia having normal hemoglobin F and hemoglobin A2 < 3.2% were inducted in the study. Ninety-three were diagnosed having IDA, whereas thirty-two were having ßTT. Ten individuals revealed other causes of anemia. The RBC count was higher, and MCV was much lower in ßTT as compared to IDA. Both groups were subjected to RDW and RDWI, however, RDWI which showed better sensitivity and specificity for ßTT. CONCLUSION: RDWI is a reliable and useful index for differentiation among IDA and ßTT, as compared to RDW.

Ruthenium Hydride Catalyzed Silylvinylation of Internal Alkynes Using Ethylene as an Additive.

An efficient synthetic strategy for the regiospecific silylvinylation of internal alkynes is described. This transformation is catalyzed by RuHCl(CO)(SIMes)PPh3 and provides a net 5-exo-dig trans-silylvinylation of internal alkynes. Ethylene was used to decrease reaction times and displayed altered selectivity at increased pressure. Furthermore, alkyl-substituted alkynes were acceptable substrates at 80 psi of ethylene.

Differentiation of reactive-like astrocytes cultured on nanofibrillar and comparative culture surfaces.

AIM: To investigate the directive importance of nanophysical properties on the morphological and protein expression responses of dibutyryladenosine cyclic monophosphate (dBcAMP)-treated cerebral cortical astrocytes in vitro. MATERIALS & METHODS: Elasticity and work of adhesion characterizations of culture surfaces were performed using atomic force microscopy and combined with previous surface roughness and polarity results. The morphological and biochemical differentiation of dBcAMP-treated astrocytes cultured on promising nanofibrillar scaffolds and comparative culture surfaces were investigated by immunocytochemistry, colocalization, super resolution microscopy and atomic force microscopy. The dBcAMP-treated astrocyte responses were further compared with untreated astrocyte responses. RESULTS & CONCLUSION: Nanofibrillar scaffold properties were shown to reduce immunoreactivity responses while poly-L-lysine-functionalized Aclar® (Ted Pella Inc., CA, USA) properties were shown to induce responses reminiscent of glial scar formation. The comparison study indicated that directive cues may differ in wound-healing versus quiescent situations.

Effects of glutathione-S-transferase polymorphisms on the risk of breast cancer: a population-based case-control study in Pakistan.

Cancer is widely accepted as one of the major health issues. Diet composition and exposure to environmental genotoxic and carcinogenic agents such as polycyclic aromatic hydrocarbons (PAHs) are among the causative factors for various types of cancers, including breast cancer. Low penetrance genes including glutathione S transferases (GST) in association with environmental factors can contribute greatly in the development of breast cancer. We were interested to investigate the association of the polymorphisms of GSTM1, GSTT1, GSTP1 and GSTO2 with the risk of breast cancer in the Pakistani population. One hundred women visiting the Department of Radiology and Oncology, Nishter Hospital, Multan with pathologically confirmed breast cancer, and 100 healthy volunteers from central Pakistan were enrolled in the present study. The strength of the association of various factors with breast cancer was measured by calculating odd ratios (ORs) which were determined by logistic regression. All P values cited are two-sided; differences resulting in a P value of less or equal to 0.05 were declared statistically significant. The Hardy Weinberg equilibrium was tested for the genotype proportions in the control group, as a measure of quality control. Those aged 36-45, in menopause or with a history of cancer in the family had a significantly higher prevalence of breast cancer compared with controls. The frequency of GSTM1 and GSTT1 was similar in both control and patients suggesting no association with the risk of cancer development, however GSTM1 and GSTT1 were significantly linked with the risk of breast cancer in smokers and in women with a history of breast cancer in the family respectively. Similarly women homozygous for GSTP1 or GSTO2 and with a history of breast cancer, or in menopause, were at greater risk of breast cancer than wild type or heterozygotes. Our data suggest that genetic differences in some GST genes may be linked with an increased susceptibility to breast cancer. Furthermore it also gives an insight into the interaction between the GST polymorphisms and pre-menopausal diagnosis of breast cancer.

Combined effect of menopause age and genotype on occurrence of breast cancer risk in Pakistani population.

UNLABELLED: 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. OBJECTIVE: 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. SUBJECTS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Frequency distribution of GSTM1 and GSTT1 null allele in Pakistani population and risk of disease incidence.

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.

Endoscopic injection of skeletal muscle-derived cells augments gut smooth muscle sphincter function: implications for a novel therapeutic approach.

INTRODUCTION: Sphincter function is a common problem in gastroenterology and leads to disorders such as GERD and fecal incontinence. OBJECTIVE: We hypothesized that transplantation of skeletal muscle-derived cells (MDCs) into GI sphincters may improve their function, leading to a more physiological approach to treating these disorders. DESIGN: We performed experiments to test the potential of MDCs to survive and differentiate within the GI smooth muscle in order to gain further knowledge on the biology of skeletal muscle transplantation in GI smooth muscle sphincters as well as to test the safety and feasibility of endoscopic injection of MDCs in a large animal model. SETTING: Animal laboratory. INTERVENTIONS: Adult male Sprague-Dawley rats and adult male beagle dogs were used. Rat-derived and dog-derived MDCs were prepared in vitro and labeled with DiI. DiI-labeled, rat-derived MDCs (200,000/4 muL phosphate buffered saline solution) were injected bilaterally in the pyloric wall of rats, and survival, differentiation, and in vitro contractility were assessed 1 month after transplantation. Dog-derived MDCs (4.0 x 10(6) cells) were also injected into the lower esophageal sphincter of 3 beagle dogs by using a standard variceal sclerotherapy needle after baseline esophageal manometry and pH monitoring. The dogs were treated with daily cyclosporine, and 2 weeks later esophageal manometry was repeated and the esophagus was examined histologically. Differentiation of grafted cells was assessed by immunofluorescence, using specific antibodies to markers of the smooth muscle phenotype (smooth muscle actin) and of the skeletal muscle phenotype (skeletal muscle myosin). RESULTS: In rats, grafted MDCs were visualized based on DiI fluorescence and were found to be localized within the muscle wall and in the muscularis mucosa. In vitro organ bath studies showed a significant increase in the contractile response of the pyloric sphincter to exogenous acetylcholine. In dogs, MDC injection resulted in a significant increase in baseline lower esophageal sphincter pressure. Further, in 1 dog with significant baseline acid reflux, MDC injection resulted in a reduction of acid reflux, with the fraction of time with pH <4 decreasing from 26.5% to 1.5%. Transplanted MDCs were seen adding bulk to the lower esophageal area and were well-integrated into the surrounding tissue. Immunofluorescence analysis revealed weak expression of skeletal muscle myosin in grafted MDCs and no expression of smooth muscle actin in either rats or dogs. LIMITATIONS: Animal study. CONCLUSION: MDCs can survive and integrate into GI smooth muscle and augment their contractile response. Thus, they may have potential for the treatment of a variety of conditions.

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).

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.

Frequency and magnitude of anxiety and depression in patients with psoriasis vulgaris.

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.

Endoscopic closure of colon perforation compared to surgery in a porcine model: a randomized controlled trial (with videos).

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.

Endoluminal suturing may overcome the limitations of clip closure of a gaping wide colon perforation (with videos).

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.

Endoluminal clip closure of a circular full-thickness colon resection in a porcine model (with videos).

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.

Frequency and pattern of psychiatric disorders in patients with vitiligo.

BACKGROUND: Vitiligo affects one to four percent of the population, regardless of age, race or sex. People with this disorder may experience emotional stress, particularly if vitiligo develops on visible areas of the body, such as face, hands, arms, feet, or on the genitals. Some feel embarrassed, ashamed, depressed, or worried about how others will react. Severel indices have been used from time to time to measure the extent of psychiatric disabilty caused by skin disorders. Regarding vitiligo, not much work has been done in Pakistan. This study was aimed to determine the frequency and pattern of psychiatric disorders amongst patients with vitiligo. METHODS: This cross sectional study was conducted in the Departments of Psychiatry and Dermatology, Ziauddin University, KDLB campus, Karachi and Institute of Surgery and Medicine, Karachi from April 2004 to March 2006. Clinically diagnosed cases of vitiligo, belonging to both sexes, aged above 15 years, fulfilling the inclusion criteria were enrolled in the study. The study was conducted in 2 stages. In the first stage, psychiatric illness was detected with the help of GHQ 12 (Urdu version), a validated tool for screening general population. In the second stage, "Psychiatric Assessment Schedule", Urdu version was administrated to every patient with high scores as per GHQ 12 to differentiate between the most frequent psychiatric disorders. All the findings were recorded, compiled and tabulated. RESULTS: A total of 100 patients comprising 62 females and 38 males ranging between 15-60 years with a mean age of 24.6 years completed the study. Exposed parts of the body were involved in 64 patients while covered sites in 36. Of the patients studied, 54 were married and 46 unmarried. In accordance with the GHQ-12 screening, 42 patients were positive for psychiatric caseness comprising 26 females and 16 males, 17 patients being married. Psychiatric caseness featured in patients below 30 years of age (28 patients) and those having exposed parts of the body being involved (27 patients). On evaluation with Psychiatric Assessment Schedule (PAS), major depressive illness (15), was the most frequent psychiatric illness followed by generalized anxiety (10), mixed anxiety and depression, social phobia, agarophobia and sexual dysfunction. CONCLUSION: Psychiatric caseness has a probable association with vitiligo, the frequency being influenced by variables of disease and life. Major depression and anxiety remain the most common psychiatric disorders in these patients.