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A Rashid

Publications and source records attributed to A Rashid.

At least 19 recordsLinked to original sources
PubMed2006

Stability of E-cadherin methylation status in gastric mucosa associated with histology changes.

BACKGROUND: We have previously shown reversal of E-cadherin methylation in gastric mucosa from patients with dyspepsia at week 6 after Helicobacter pylori-eradication therapy. But the long-term methylation status of these patients was unknown. AIM: To investigate the methylation status at E-cadherin at year 3 after H. pylori-eradication therapy. METHODS: 35 patients (25 with and 10 without H. pylori eradicated) enrolled in our previous study were recruited into the present study (year 3 analysis). Methylation at E-cadherin was evaluated by methylation-specific polymerase chain reaction method. RESULTS: There was no difference in age and sex distribution in the two groups. Methylation at E-cadherin in patients with H. pylori eradicated at weeks 0, 6 and year 3 were 52%, 20% and 20%, respectively. Concordant methylation status at week 6 and year 3 was 92%. Methylation at E-cadherin in patients without H. pylori at weeks 0, 6 and year 3 were 50%, 60% and 60%, respectively. Concordant methylation status between week 6 and year 3 was 90%. Stability of E-cadherin methylation status was associated with histological changes. No association between E-cadherin methylation status and age was observed. CONCLUSION: The methylation pattern is stable for a long period, thus suggesting the effect of environment on methylation.

Anti-Bacterial Agents↗
PubMed2006

CSF -neurofilament correlates with outcome after aneurysmal subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating event. Following the bleeding, a number of pathophysiological changes and clinical factors determine outcome. Not surprisingly, attempts to predict outcome based on a single factor have failed. The neurological status graded at admission to hospital and distributions of the blood on CT are the strongest predictors. There is evidence that cerebrospinal fluid (CSF) proteins may serve as markers of the extent of brain damage. The present study is focused on the light unit of neurofilament protein (NFL), previously not evaluated in aSAH. Lumbar puncture (LP), neurological grading according to World Federation of Neurological Surgeons (WFNS) and neurological examination according to the National Institute of Health Stroke Scale (NIHSS) were performed in 48 consecutive patients with aSAH 10-14 days after the hemorrhage. CSF-NFL concentrations were analyzed using an ELISA. Outcome was assessed after 1 year and categorised according to the extended Glasgow Outcome Scale (GOSE). A significant correlation between CSF-NFL and GOSE was detected at follow up after 1 year. CSF-NFL also correlated with WFNS and NIHSS on the day of the lumbar puncture. CSF-NFL is a biochemical marker of brain damage correlating to neurological status and long-term outcome after aneurysmal subarachnoid hemorrhage.

Adult↗
PubMed2006

Critical interactions between TGF-beta signaling/ELF, and E-cadherin/beta-catenin mediated tumor suppression.

Inactivation of the transforming growth factor-beta (TGF-beta) pathway occurs often in malignancies of the gastrointestinal (GI) system. However, only a fraction of sporadic GI tumors exhibit inactivating mutations in early stages of cancer formation, suggesting that other mechanisms play a critical role in the inactivation of this pathway. Here, we show a wide range of GI tumors, including those of the stomach, liver and colon in elf+/- and elf+/- / Smad4+/- mutant mice. We found that embryonic liver fodrin (ELF), a beta-Spectrin originally identified in endodermal stem/progenitor cells committed to foregut lineage, possesses potent antioncogenic activity and is frequently inactivated in GI cancers. Specifically, E-cadherin accumulation at cell-cell contacts and E-cadherin-beta-catenin-dependent epithelial cell-cell adhesion is disrupted in elf+/- / Smad4+/- mutant gastric epithelial cells, and could be rescued by ectopic expression of full-length elf, but not Smad3 or Smad4. Subcellular fractionation revealed that E-cadherin is expressed mainly at the cell membrane after TGF-beta stimulation. In contrast, elf+/- / Smad4+/- mutant tissues showed abnormal distribution of E-cadherin that could be rescued by overexpression of ELF but not Smad3 or Smad4. Our results identify a group of common lethal malignancies in which inactivation of TGF-beta signaling, which is essential for tumor suppression, is disrupted by inactivation of the ELF adaptor protein.

Animals↗
PubMed2006

Eradication of Helicobacter pylori infection reverses E-cadherin promoter hypermethylation.

BACKGROUND: E-cadherin methylation is important in gastric carcinogenesis. Reversing hypermethylation may halt the carcinogenic process. We have previously reported that Helicobacter pylori infection is associated with E-cadherin methylation in chronic gastritis patients. AIM: To examine if eradication of H pylori could reverse E-cadherin methylation. METHODS: Patients with dyspepsia and positive for H pylori infection, with a mucosal biopsy showing chronic active gastritis, were randomised to receive H pylori eradication therapy (group 1, n = 41) or no treatment (group 2, n = 40), and were followed up prospectively. Gastric mucosae were taken for methylation assay at week 0 (before treatment) and week 6 (after treatment). Archived specimens of intestinal metaplasia with H pylori infection (n = 22) and without (n = 19) were retrieved for methylation analysis. Methylation was assessed using methylation specific polymerase chain reaction and sequencing. RESULTS: Methylation at E-cadherin was detected in 46% (19/41) and 17% (7/41) of patients at weeks 0 and 6, respectively, in group 1 (p = 0.004); 78.9% (15/19) of specimens were unmethylated after eradication of H pylori. Mucosal biopsy showed chronic inactive gastritis in 35 patients, intestinal metaplasia in one, and normal mucosa in five at week 6. Methylation was detected in 47.5% (19/40) and 52.5% (21/40) of patients at weeks 0 and 6, respectively, in group 2 (P = 0.5). Gastric mucosal biopsy showed persistent chronic active gastritis in all cases. Methylation frequency did not differ in H pylori positive or negative intestinal metaplastic specimens (72.7% v 63%; p = 0.5). CONCLUSION: H pylori eradication therapy could reverse methylation in patients with chronic gastritis. This demonstrates an environmental effect on methylation.

Amoxicillin↗
PubMed2006

Psychiatric assessment of patients with self-inflicted lacerations to the wrist and forearm admitted to a nonpsychiatric ward: the experience of a regional plastic surgery unit.

In 1984, the Department of Health (DoH) recommended that all patients with deliberate self-harm (DSH) must have a mental assessment before discharge. DSH patients, especially those with lacerations to wrist and forearm, are a regular source of admission to plastic surgery units. In Northern Ireland, the regional plastic surgery service is provided at the Ulster Hospital, which does not have an on-site psychiatric department. Consequently, it was often difficult to arrange a psychiatrist assessment for these patients on the ward even when the assessment was required urgently. The objective of this study was to develop and validate a protocol that would ensure that these patients were assessed and followed up for their mental health as recommended by the DoH. In the absence of clear guidelines from the DoH and utilising the existing arrangement between Accident and Emergency (A&E) and the psychiatric services, all referring A&E departments were instructed at the time of referring patients with DSH to wrist and forearm to arrange a psychiatric examination before transferring the patient to the plastic surgery unit. Data were collected retrospectively (August 2002-October 2002) and prospectively (November 2002-October 2003) and comprised demographic features, previous history of self-harm, conduct of the patient in A&E and the ward, length of stay in the hospital and various aspects of psychiatric assessment and follow-up. In total, 42 referrals were made during the period studied. The average age was 28 years with a male to female ratio of 2:1. The average hospital stay was two days. Despite difficulties, our practice was found effective in ensuring psychiatry assessment and follow-up without risking the patient's physical health. The study also highlighted the need for collaboration between plastic surgeons and psychiatrists to improve services in regards to DSH patients.

Adolescent↗
PubMed2005

Severe paediatric pulmonary hypertension: new management strategies.

Pulmonary hypertension is a significant complication in many paediatric disease states. This article discusses current understanding of pulmonary hypertension and includes definition, diagnosis, and management. A description of the latest advances in targeted pharmacological therapy in children is also provided as well as impact on morbidity and mortality.

Anticoagulants↗
PubMed2004

Breast necrosis following harvest of internal mammary artery.

The use of internal mammary artery is well established not only in cardiac surgery for coronary artery bypass grafting but also in plastic surgery for breast reconstruction with free autologus tissue. The complications that follow harvest of internal mammary artery for heart surgery usually relate to the wound. This case report documents the first case of complete breast infarction following such a procedure in a patient who had no prior history of breast pathology. The histology of the breast showed extensive calcification of the intima and media of small to medium sized vessels, a condition called calciphylaxis, which is largely unknown outside the fields of nephrology and dermatology.

Breast↗
PubMed2004

Significance of post-chemoradiation biopsy in predicting residual esophageal carcinoma in the surgical specimen.

Pathologic complete response in the resected esophagus can be achieved in approximately 30% of patients with locally advanced esophageal or gastroesophageal junction carcinoma after preoperative chemoradiation therapy. These patients tend to have a longer survival than those who have less than pathologic complete response. Post-chemoradiation esophageal biopsy (PCEB) is used to check for the presence of residual tumor before a definitive resection is performed, but the clinical significance of PCEB findings is not clear due to the possibility of sampling bias and the superficial nature of the specimen obtained. We evaluated the use of PCEB (defined as biopsy taken within 30 days before esophagectomy) in predicting residual cancer in post-treatment esophagectomy specimens. PCEB was performed in 65 of 183 (36%) patients with locally advanced esophageal or gastroesophageal junction carcinoma, who received preoperative chemoradiation therapy. The cancer status in PCEB was correlated with the residual cancer in the esophagectomy specimens. PCEB had no cancer in 80% (52 of 65) of patients (Bx-negative) and cancer in 20% (13 of 65) of patients (Bx-positive). There was no difference in the presence of residual cancer (either in esophagus or lymph node) in esophagectomy specimens between Bx-negative patients (77%, 40 of 52) or Bx-positive patients (92%, 12 of 13), P = 0.44. The positive predictive value of biopsy was 92% (12 of 13), negative predictive value 23% (12 of 52), sensitivity 23% (12 of 52) and specificity 92% (12 of 13). There was no difference in the residual cancer staging in the esophagectomy specimen between Bx-positive and Bx-negative patients. In contrast, residual metastatic carcinoma in lymph nodes was more frequent in Bx-positive patients (69.2%, 9 of 13) than in Bx-negative patients (28.8%, 15 of 52), P = 0.01. Our data suggest that PCEB is a specific but not a sensitive predictor of residual cancer following esophagectomy. Bx-positive patients tend to have more frequent residual tumor in lymph nodes. The utility of PCEB in predicting residual cancer in the lymph nodes needs to be explored further along with molecular predictors of response to preoperative therapy.

Biopsy, Needle↗
PubMed2003

An analysis of calls to an out-of-hours palliative care advice line.

An advice line was set up by a specialist palliative care hospice to improve the provision of out-of-hours palliative care to primary care teams, i.e. from 17.00 to 09.00 h during the week and at weekends and bank holidays. A senior member of nursing staff or medical staff answered all calls. During the first year of operation, 98 calls were received. The majority of callers were GPs (55%) and community nurses (34%). The advice requested was largely related to management of pain and the use of opiates, e.g. breakthrough dose of opiates and conversion of drugs to syringe drivers. Recommendations from this study include the provision of continuing education on management of terminally ill patients, and improved communication between primary care teams, providers of out-of-hours primary care and specialist palliative care teams.

Holidays↗
PubMed2003

Promoter methylation of E-cadherin gene in gastric mucosa associated with Helicobacter pylori infection and in gastric cancer.

BACKGROUND: E-cadherin is an adhesion molecule involved in tumour invasion/metastasis. Silencing of E-cadherin by promoter CpG methylation has been shown in both familial and sporadic gastric cancers. Helicobacter pylori is a class I carcinogen in gastric cancer. AIMS: This study was undertaken to investigate the association between methylation of E-cadherin and H pylori in gastric mucosa from dyspeptic patients, and in intestinal metaplasia and primary and metastatic adenocarcinoma from surgical specimens of patients with gastric cancer. METHODS: E-cadherin methylation was studied using methylation specific polymerase chain reaction in microdissected tissue from biopsies or surgical resection specimens. E-cadherin expression was studied by immunohistochemistry. RESULTS: E-cadherin methylation was present in 31% (11/35) of gastric mucosae from dyspeptic patients, and was associated with H pylori infection (p=0.002), but was independent of the age of the patient or presence or absence of gastritis. E-cadherin methylation was present in 0% (0/8) of normal mucosa, 57% (12/21) of intestinal metaplasias, and 58% (15/26) of primary and 65% (21/32) of metastatic cancers. E-cadherin methylation status was concordant in 92% (11/12) of intestinal metaplasias and primary cancers, and in 85% (17/20) of primary and metastatic cancers from the same resected specimen. E-cadherin methylation in gastric cancer was associated with depth of tumour invasion (p=0.02) and regional nodal metastasis (p=0.05). CONCLUSION: E-cadherin methylation is an early event in gastric carcinogenesis, and is initiated by H pylori infection.

Adenocarcinoma↗
PubMed2002

Acute myocardial infarction: profile and management at a tertiary care hospital in Karachi.

OBJECTIVE: Acute Myocardial Infarction (AMI) is a rising epidemic in developing countries. While studies in the West have established the characteristics and management of AMI patients, comprehensive data reflecting these issues in the Pakistani subjects is scarce. This study examined the profile and management of AMI in patients hospitalized at a tertiary care hospital in Karachi, Pakistan. METHODS: Three hundred forty four patients admitted in 1998 with the diagnosis of AMI met our inclusion criteria. Data on presentation, investigations, monitoring and therapy was obtained. Chi-square and t tests were used to analyze the data. RESULTS: Out of 344 patients with AMI, 71% were males; 58% had a Q wave MI. Majority of the patients who presented within 2 hours of symptom onset (36%), had chest pain. Patients with dyspnea and no chest pain were more likely to present after 12 hours of the onset of symptoms. In-house mortality was found to be 10.8%. Low HDL and diabetes was associated with in-hospital complications. Twenty nine percent of patients were given thrombolytic therapy with a mean door-to-needle time of 1 hour 36 minutes; 33% of patients who were eligible of Streptokinase did not receive it. Cardiac catheterization was performed in 28% patients. Echocardiography and Exercise Tolerance Test, both under utilized, were performed in 67% and 16% of patients, respectively. Two hundred sixteen (70%) patients discharged from hospital were contacted via telephone and the 1-year mortality rate among them was 28%. CONCLUSION: The profile and management of AMI was in coherence with earlier, Western studies. Chest pain units need to be established in the Emergency Room. Patients should be risk stratified prior to discharge. Public awareness regarding primary and secondary prevention and symptoms of AMI needs to be increased.

Adult↗
PubMed2002

An evaluation of cefaclor in Pakistani children with pharyngotonsillitis.

OBJECTIVE: To assess the efficacy, safety of cefaclor for the treatment of pharyngotonsillitis in Pakistani children. METHOD: Pakistani children between the ages of two to twelve years and diagnosed with pharyngotonsillitis were eligible to participate in the study. Cefaclor was administered three times daily for a total dose of 20-40 mg/kg/day, depending on the severity of the infection, for 7 days. Patients were evaluated on the basis of symptomatic response and antibiotic susceptibility pattern as a result of bacteriological examination. RESULTS: Based on observed pre-therapy signs/symptoms of infection with pharyngotonsillitis, 99% of patients (95% CI=94.9% to 100.0%) were reported as having a symptomatic response of Cure or Improvement by end of study. Group A b-haemolytic Streptococci was the most prevalent pathogen isolated pre-therapy (occurring in 45% of patients). Of all patients for whom this pathogen was isolated, 64% had complete eradication by end of therapy, while there was persistence or superinfection in 36% of patients. Only 9 occurrences of non-serious adverse events were observed among 7 of the 107 patients, including diarrhea (5), nausea (1), vomiting (1), rash (1) and stomatitis (1). CONCLUSION: Based on the high symptomatic response rate of 99% and the positive safety data, cefaclor was found to be effective and safe in treating Pakistani children with pharyngotonsillitis.

Anti-Bacterial Agents↗
PubMed2001

Instabilotyping: comprehensive identification of frameshift mutations caused by coding region microsatellite instability.

Coding region frameshift mutation caused by microsatellite instability (MSI) is one mechanism contributing to tumorigenesis in cancers with MSI in high frequency. Mutation of TGFBR2 is one example of this process. To identify additional examples, a large-scale genomic screen of coding region microsatellites was conducted. 1115 coding homopolymeric loci with six or more nucleotides were identified in an online genetic database. Mutational screening was performed at 152 of these loci in 46 colorectal tumors with MSI in high frequency. Nine loci were mutated in > or =20% of tumors, 10 loci in 10-20%, 24 loci in 5-10%, 43 loci in <5%, and 66 loci were not mutated in any tumors. The most frequently mutated novel loci were the activin type II receptor gene (58.1%), SEC63 (48.8%), AIM 2 (47.6%), a gene encoding a subunit of the NADH-ubiquinone oxidoreductase complex (27.9%), a homologue of mouse cordon-bleu (23.8%), and EBP1/PA2G4 (20.9%). This genome-wide approach identifies coding region MSI in genes or pathways not implicated previously in colorectal tumorigenesis, which may merit functional study or other additional analysis.

3' Untranslated Regions↗
PubMed2001

Biallelic inactivation of the APC gene is associated with hepatocellular carcinoma in familial adenomatous polyposis coli.

BACKGROUND: Certain primary hepatic tumors have been associated with familial adenomatous polyposis (FAP), a condition caused by germline mutations of the adenomatous polyposis coli (APC) gene. However, a genetic association between FAP and hepatocellular carcinoma (HCC) has not been shown. This study tested the hypothesis that biallelic inactivation of the APC gene contributed to the development of HCC in a patient with FAP and a known germline mutation of the APC gene at codon 208, but no other risk factors for HCC. METHODS: Total RNA and genomic DNA were isolated from the tumor, and in vitro synthesized protein assay and DNA sequencing analysis were used to screen for a somatic mutation in the APC gene. RESULTS: A somatic one-base pair deletion at codon 568 was identified in the wild-type allele of the APC gene. CONCLUSIONS: To the authors' knowledge, this study provides the first evidence that biallelic inactivation of the APC gene may contribute to the development of HCC in patients with FAP.

Adenomatous Polyposis Coli↗
PubMed2001

Mylotarg (gemtuzumab ozogamicin) therapy is associated with hepatic venoocclusive disease in patients who have not received stem cell transplantation.

BACKGROUND: Mylotarg (Wyeth-Ayerst Laboratories, St. Davids, PA) is the brand name for a calicheamicin-conjugated humanized anti-CD33 monoclonal antibody (gemtuzumab ozogamicin, CMA-676) and has been approved recently for the treatment of a subset of elderly patients who have relapsed acute myeloid leukemia (AML). Mylotarg is associated with an incidence of approximately 20% Grade 3 or 4 hyperbilirubinemia and liver transaminitis in this patient population. Hepatic venoocclusive disease (VOD) has been reported in patients who have undergone stem cell transplantation (SCT) after Mylotarg therapy. Outside of the SCT setting, VOD has been associated very rarely with cytotoxic therapy. METHODS: The authors assessed the incidence of VOD in 119 patients who were receiving Mylotarg-containing non-SCT regimens. VOD was diagnosed through the use of standard Seattle and Baltimore criteria. RESULTS: A cohort of 119 (61 previously untreated, 58 with relapsed disease) patients with AML (92 patients), advanced myelodysplastic syndrome (25 patients), or chronic myeloid leukemia in blast phase (2 patients), received Mylotarg-based regimens. Fourteen (12%) developed VOD. The diagnosis of VOD was supported by histology in 2 patients and radiologic studies in a further 10 patients. Five (36%) of 14 patients with VOD had received no prior antileukemic cytotoxic therapy, including 2 patients who received single-agent Mylotarg therapy. CONCLUSIONS: Mylotarg was shown to be associated with the development of potentially fatal VOD in patients with leukemia who had not received SCT. VOD occurred when Mylotarg was used either as a single agent or when it was given with other cytotoxic agents. VOD occurred in Mylotarg-treated patients who had received no prior cytotoxic therapy. The current study concluded that risk factors for VOD should be assessed when considering Mylotarg therapy, and that attempts to avoid and treat VOD are warranted in patients who receive Mylotarg therapy.

Adolescent↗