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Biomedical subjects

M Rashid

Publications and source records attributed to M Rashid.

At least 19 recordsLinked to original sources

Immunohistochemistry increases the accuracy of diagnosis of benign papillary lesions in breast core needle biopsy specimens.

AIMS: Recent studies have suggested that benign papillary lesions without atypia [benign papilloma (BP)] diagnosed on breast core needle biopsy (CNB) may not require excision. However, most have studied only small numbers of cases and scant data are available on the utility of immunohistochemistry in the categorization of papillary lesions on CNB. In the largest published series of BP identified on CNB, we studied the impact of immunohistochemistry on the accuracy of a CNB diagnosis of BP. METHODS AND RESULTS: Breast CNBs (n = 129) with a diagnosis of papillary lesion were immunostained for calponin, p63 and cytokeratin 5/6. Haematoxylin and eosin and immunostained slides were independently reviewed by four breast pathologists. BP was the final excision diagnosis in 35 cases. With the use of immunohistochemistry, the positive predictive value (PPV) of BP diagnosis by the four individual pathologists increased from 72.7-83.3% (mean 79.2%) to 77.8-87.5% (82.1%), the negative predictive value (NPV) increased from 77.8-98.5% (88.6%) to 100% for all four participants and overall accuracy increased from 78.7-92.6% (84.7%) to 90.7-95.4% (92.8%). No case of invasive carcinoma was diagnosed as BP on CNB by any participant. The frequency of ductal carcinoma in situ following a BP diagnosis on CNB ranged from 2.5% to 4.8% (4%) but was only 0-3% (2.3%) after excluding cases that were radiologically suspicious for malignancy. CONCLUSIONS: Immunohistochemistry increases accuracy of BP diagnosis in CNB specimens. Benign papillary lesions diagnosed on CNB do not require excision in the absence of suspicious clinical/radiological findings.

Adult↗

The impact of a gluten-free diet on adults with coeliac disease: results of a national survey.

UNLABELLED: OBJECTIVE We sought to evaluate the impact of the gluten-free diet on the 5,240 members of the Canadian Celiac Association (CCA). Data are presented on 2,681 adults (>or=16 years) with biopsy-proven celiac disease (CD). METHODS: A mail-out survey was used. Quality of life was evaluated using the 'SF12', and celiac-specific questions. RESULTS: Mean age was 56 years, mean age at diagnosis was 45 years, and 75% were female. The 'SF12' summary scores were similar to normative Canadian data, but were significantly lower for females and newly diagnosed patients. Respondents reported: following a gluten-free (GF) diet (90%), improvement on the diet (83%), and difficulties following the diet (44%), which included: determining if foods were GF (85%), finding GF foods in stores (83%), avoiding restaurants (79%), and avoiding travel (38%). Most common reactions to consumed gluten (among 73%) included pain, diarrhea, bloating, fatigue, nausea, and headache. Excellent information on CD and its treatment was provided by the CCA (64%), gastroenterologists (28%), dietitians (26%) and family doctor (12%). CONCLUSIONS: Quality of life in those with CD could be increased with early diagnosis, increased availability of gluten-free foods, improved food labelling, and better dietary instruction. Education of physicians and dietitians about CD and its treatment is essential.

Canada↗

Observer variability in the histopathological reporting of core biopsies of papillary breast lesions is reduced by the use of immunohistochemistry for CK5/6, calponin and p63.

AIM: To investigate agreement on core biopsy diagnosis of papillary breast lesions, which is acknowledged as a difficult area, and to determine the effect of the use of immunohistochemistry (IHC) to assist diagnosis. STUDY DESIGN: Haematoxylin and eosin (H&E) sections of 129 core biopsies of papillary breast lesions were circulated to four observers who categorized each case as: B2 (benign), B3a (epithelial proliferation, probably benign but requiring biopsy), B3b (epithelial proliferation with cytological or architectural atypia), B4 (probably malignant but insufficient material or artefact to allow diagnosis), B5 (malignant papillary lesion). In all cases (n = 127) IHC was performed for cytokeratin (CK) 5/6, calponin, p63 (myoepithelial markers), and slides recirculated. RESULTS: There was unanimous agreement in 44% of cases on H&E only which rose to 91% after the use of IHC. Overall, unweighted kappa (Ku; five categories) rose from 0.54 to 0.91. The main effect of IHC was to reduce the use of intermediate categories (B3a, B3b and B4) and allow definitive diagnosis (B2 or B5). CONCLUSION: Agreement on H&E sections alone in papillary core biopsies of breast is only 44% (Ku = 0.54) but is significantly increased to 91% (Ku = 0.91) by the use of IHC for CK5/6, calponin and p63.

Biomarkers, Tumor↗

Evaluation of a protocol for examining nephrectomy specimens with renal cell carcinoma.

AIMS: To evaluate the practicality of use and the effectiveness of a standard protocol for examining nephrectomy specimens for renal cell carcinoma (RCC), with emphasis on the identification of vascular invasion. METHODS: A standard protocol, devised to identify the major prognostic determinants, was used to examine 79 consecutive tumours submitted to four histopathology departments. The incidence of vascular invasion found was compared with the incidence in a historical series of tumours. RESULTS: The protocol proved easy to follow, and appeared to increase the incidence of observed vascular invasion (40 of 69 cases compared with 69 of 176 cases in the historical series; p = 0.059, Fishers exact test, one sided) CONCLUSIONS: If pathological prognostic determinants are to be used for clinical management, then it is important that they are identified and recorded consistently. The protocol described provides a method of examining nephrectomy specimens that can be used in routine practice and would probably reliably identify recognised prognostic variables.

Carcinoma, Renal Cell↗

Comparison of local povidone-iodine antisepsis with parenteral antibacterial prophylaxis for prevention of infective complications of TURP: a prospective randomized controlled study.

OBJECTIVE: To determine whether antisepsis with povidone-iodine solution applied at the external urethral meatus confers protection against infective complications following transurethral resection of the prostate (TURP) and compare that with antibacterial prophylaxis. METHODS: A total of 167 patients with sterile urine undergoing TURP for benign prostatic hyperplasia (BPH) were prospectively randomized into three groups. Group A, had gauze soaked in saline applied at the urethral meatus (control group). In group B, the gauze was soaked in povidone-iodine instead of saline and group C had a single 1 g i.v. injection of cephradine at induction of anaesthesia with no treatment for the meatus. Bacteraemia, post-operative bacteriuria and other infective complications were compared in the three groups. Associations of bacteriuria at catheter removal and intra-operative bacteraemia with infective complications and with long term bacteriuria were also studied. RESULTS: Bacteriuria rate at catheter removal was not significantly different in the three groups. However, intraoperative bacteraemia and bacterial growth at the external urethral meatus was significantly lower in group C. Bacteriuria at catheter removal was significantly associated with bacterial growth at the meatus but not with long term bacteriuria at 3 months. Bacteriuria at catheter removal could not accurately predict infective complications. CONCLUSION: Post-TURP bacteriuria appears to be preceded by bacterial growth at the external urethral meatus. Antisepsis with povidone-iodine solution application at the meatus does not confer adequate protection against meatal bacterial growth as that obtained by prophylactic antibacterials. Nonetheless, neither antibacterial prophylaxis nor local antisepsis could reduce bacteriuria rate in this study.

Administration, Topical↗

Treatment of vitamin K deficiency in cystic fibrosis: Effectiveness of a daily fat-soluble vitamin combination.

OBJECTIVE: Patients with cystic fibrosis (CF) and pancreatic insufficiency (PI) commonly have vitamin K deficiency, and those with CF-associated liver disease (CFLD) have universal vitamin K deficiency. We evaluated the effectiveness of an oral fat-soluble vitamin combination (ADEKs) to treat patients with vitamin K deficiency. STUDY DESIGN: Patients with PI and CF (mean age, 15 years; range, 0.6 to 46 years) including 6 with advanced CFLD were prospectively enrolled in a study of a fat-soluble vitamin combination taken on a daily basis. None had received vitamin K supplementation for at least 4 months before the study. Fat-soluble vitamin combination supplementation was given for a minimum of 4 months; the mean vitamin K intake was 0.18 mg/d (SD = 0.1, range, 0 to 0.3). The primary outcome was change in plasma PIVKA-II (prothrombin in vitamin K absence). RESULTS: Before supplementation 58 (81%) of 72 patients had abnormal PIVKA-II levels (>2.9 ng/mL). After supplementation 29 (40%) had abnormal PIVKA-II levels (P =.001). All 6 patients with advanced CFLD had abnormal PIVKA-II levels (median, range of 20.8, 5.5 to 55 ng/mL) before treatment, which corrected to normal in 50% (4.1, 2.1 to 65 ng/mL). Four patients, 2 with CFLD, had a prolonged prothrombin time (>13.5 seconds) at both time periods. CONCLUSIONS: An oral fat-soluble vitamin combination with a modest amount of vitamin K can, as a daily supplement, improve the PIVKA-II levels in patients with PI and CF.

Adolescent↗

Aerosol particle and organic vapor concentrations at industrial work sites in Malaysia.

The objective of this study was to establish baseline data about air pollutants potentially related to nasopharyngeal carcinoma (NPC) in the Federal Territory and Selangor, Malaysia. During 1991-1993, ambient air quality was monitored at 42 work sites representing ten industrial sectors: adhesive manufacturing, foundries, latex processing, metalworking, plywood/veneer milling, ricemilling, rubber tire manufacturing, sawmilling, shoemaking, and textile related industries. At each work site, aerosol particle size distributions and concentrations of formaldehyde, benzene, toluene, isopropyl alcohol, and furfural were measured. Mean aerosol particle concentrations ranged from 61 micrograms/m3 in foundries to 5,578 micrograms/m3 in ricemills, with five industries (adhesives, metalworking, ricemilling, sawmilling, and shoemaking) exceeding the US EPA 24-hr ambient air standard for PM-10. Formaldehyde concentrations exceeded the threshold limit value (TLV) in adhesives factories. Other vapours and elements measured were well below TLVs.

Aerosols↗

Binding affinity of a newly synthesized 5-HT2 antagonist, AT-1015 (N-[2-[4-(5H-Dibenzo[a,d]cyclohepten-5-ylidene)-piperidino]ethyl]-1-formyl-4-piperidinecarboxamide monohydrochloride monohydrate), in the rabbit platelet membrane.

The object of this study was to investigate the binding affinity of a newly synthesized 5-HT2 antagonist, (N-[2-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-piperidino]ethyl]-1-formyl-4-piperidinecarboxamide monohydrochloride monohydrate) (AT-1015), in the rabbit platelet membrane using [3H]-ketanserin by radioligand binding assay method and to compare the results with other selective 5-HT2 antagonists. The results showed that AT-1015 displayed high affinity to 5-HT2 receptors in rabbit platelet membranes. The pKi value of AT-1015 was 7.40, which is slightly lower than that of ketanserin, but higher than that of cyproheptadine. On the other hand, the displacement potency of AT-1015 for 5-HT2 receptors in rabbit platelets was similar to those of sarpogrelate and ritanserin. This is the first report of the high affinity of AT-1015 in rabbit platelets.

Animals↗

Assessment of affinity and dissociation ability of a newly synthesized 5-HT2 antagonist, AT-1015: comparison with other 5-HT2 antagonists.

This study investigated the binding affinities of a newly synthesized 5-HT2 antagonist, AT-1015 (N-[2-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-piperidino]ethyl]-1-formyl-4-piperidinecarboxamide monohydrochloride monohydrate) for [3H]ketanserin bindings to 5-HT2 receptors in the rabbit cerebral cortex membranes using the radioligand binding assay method. The affinity of this compound was also compared with other 5-HT2-selective antagonists such as ketanserin, sarpogrelate, cyproheptadine and ritanserin, and the results showed that AT-1015 has a high pKi value for the 5-HT2 receptor. The rank order of these antagonists are: ritanserin > ketanserin approximately equal to AT-1015 > cyproheptadine approximately equal to sarpogrelate. We also evaluated the dissociation ability (slow or rapid) of AT-1015 in the rabbit cerebral cortex membrane and compared it with other 5-HT2 antagonists using the radioligand binding assay method. The blockade of [3H]ketanserin binding sites in the rabbit cerebral cortex induced by ketanserin and sarpogrelate was readily reversed by washing, whereas the inhibition by AT-1015, cyproheptadine and ritanserin was not readily reversed by washing. The % of control after washing are 76.10% and 49.55% for AT-1015 at 10(-7.5) and 10(-7.0) M, 67.32% and 50.17% for cyproheptadine at 10(7.5) and 10(-7.0) M, and 72.38% and 39.80% for ritanserin at 10(-9.5) and 10(-9.0) M concentrations, respectively. Thus, these findings suggest that AT-1015 has antagonistic properties towards the 5-HT2 receptor and also shows that AT-1015 slowly dissociates from the 5-HT2 receptor, whereas, ketanserin and sarpogrelate dissociate rapidly from the 5-HT2 receptor, which do not correlate with their affinity.

Animals↗

Factors affecting fertility following radical versus conservative surgical treatment for tubal pregnancy.

OBJECTIVE: The aim of this study was to analyze the fertility prognosis after conservative or radical surgery for ectopic pregnancy. Also, to identify any biological factors that may influence the fertility outcome after an ectopic pregnancy. METHODS: A retrospective study which was carried out by collating information from the patient's hospital records was performed on 137 cases of confirmed ectopic pregnancy between January 1990 and December 1995 at the Security Forces Hospital Riyadh, Kingdom of Saudi Arabia. The outcome measure of term pregnancy rate and repeat ectopic pregnancy rate was analyzed up to 3 years after the diagnosis of index ectopic pregnancy. RESULTS: Our results showed that the term pregnancy rates were not significantly different following radical or conservative surgical treatments for ectopic pregnancy, P > 0.05, (50% in the conservative group compared with 56% in the radical group). But equally important, the risk of a further ectopic was not increased in the radical surgery group, P >0.05 (11% in the conservative group as compared to 8% in the radical group). The incidence of intrauterine pregnancy rate (term pregnancy + miscarriage) was also comparable in each group. Multivariate regression analysis showed that the factors associated with higher fertility were age 30 years or less, past history of term pregnancy and a negative history of infertility (P < 0.05). CONCLUSION: No significant difference in intrauterine pregnancy rates or repeat ectopic pregnancy rates were found after radical or conservative surgical treatment for tubal pregnancy. The patient's age, previous obstetric performance and a history of infertility significantly influenced fertility following the index ectopic pregnancy.

Abortion, Spontaneous↗

Nonalcoholic steatohepatitis in children.

BACKGROUND: Nonalcoholic steatohepatitis occurs commonly in adults with obesity or diabetes mellitus. There are only a few reports of this condition in children. METHODS: Prospective consecutive clinical series. RESULTS: Between December 1985 and April 1995, 36 children (21 boys, 15 girls) were diagnosed with nonalcoholic steatohepatitis at the Hospital for Sick Children, Toronto. The median age at diagnosis was 12 years (range, 4-16 years). Most patients were referred because of elevated serum aminotransferases or abnormal hepatic sonogram. Thirty patients (83%) were obese. Two patients had diabetes mellitus at diagnosis, and it developed later in two. Fifteen patients had palpable hepatomegaly, and one of these had splenomegaly. None had physical signs of chronic liver disease. Thirteen of 36 patients had acanthosis nigricans. Serum aminotransferases were elevated in all but one patient. Tests for Wilson disease and chronic hepatitis B and C were negative. Serum lipid profiles were abnormal in 18 patients: 7 had hypercholesterolemia, and 11 had hypertriglyceridemia. Twenty-four of 31 examined had abnormal liver sonograms suggestive of fatty infiltration. Twenty-four patients underwent percutaneous liver biopsy: all showed large-droplet fat. Inflammation was present in 88% and fibrosis-cirrhosis in 75%. One 10-year-old patient had established cirrhosis at diagnosis. CONCLUSIONS: Nonalcoholic steatohepatitis occurs in children, is clinically diverse, and may not be benign.

Acanthosis Nigricans↗

A novel 5-HT(2) antagonist, sarpogrelate hydrochloride, shows inhibitory effects on both contraction and relaxation mediated by 5-HT receptor subtypes in porcine coronary arteries.

In isolated porcine coronary arteries, concentrations of 5-HT (10(-8) to 3x10(-5) mol/l), alpha-methylserotonin (alpha-Me-5-HT, 10(-8) to 3x10(-5) mol/l) and ergonovine (10(-9) to 3x10(-4) mol/l) produced contraction, whereas high concentrations (10(-5) to 10(-4) mol/l) of these drugs produced relaxation. Both sarpogrelate and ketanserin produced rightward shifts of contraction concentration-response curves induced by 5-HT and alpha-Me-5-HT at the concentration from 10(-9) to 3x10(-5) mol/l, and only sarpogrelate inhibited the relaxation at high concentrations of 5-HT and displayed 155% of maximal contraction at 10(-4) mol/l 5-HT. On the other hand, sarpogrelate and ketanserin did not show any inhibitory effects on the relaxation induced by high concentrations of ergonovine. These results suggested that sarpogrelate and ketanserin show different inhibitory effects on the relaxation induced by high concentrations of 5-HT, indicating that these two drugs may have different affinities to 5-HT receptor subtypes that may be involved in relaxation.

Animals↗

Inhibitory effects of a newly synthesized 5-HT2 receptor antagonist, AT-1015 (N-[2-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidino]-ethyl]-1-for myl-4-piperidinecarboxamide monohydrochloride monohydrate), on contraction and relaxation of pig coronary arteries induced by 5-HT and alpha-methylserotonin: comparison with ketanserin.

Inhibitory effects of a newly synthesized 5-HT2 receptor antagonist, AT-1015 (N-[2-[4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidinolethyl ]-1-formyl-4-piperidinecarboxamide monohydrochloride monohydrate) on contraction and relaxation of coronary arteries of pig hearts mediated by 5-HT2 subtypes were evaluated and these results were compared with those of ketanserin. Contraction and relaxation were determined by adding 5-HT or alpha-methylserotonin (alpha-Me-5-HT) as agonists. Although ketanserin induced rightward shifts of contraction, AT-1015 inhibited the maximal response. In addition, ketanserin inhibited relaxation induced by high concentration of agonists, but there were no inhibitory effects of AT-1015 on relaxation. Thus, these results suggest that AT-1015 is a strong non-competitive 5-HT2 antagonist in porcine coronary arteries and that this drug clearly exhibited different effects on the contraction and relaxation of coronary arteries of pig hearts from those of ketanserin.

Animals↗

The use of rectal diclofenac for post-cesarean analgesia.

OBJECTIVE: To determine whether the prophylactic use of rectal diclofenac sodium produces effective analgesia after cesarean section. METHODS: A randomized single blind controlled trial. The study period was from September 1997-April 1998. Forty patients undergoing both emergency and elective cesarean section were studied, with 20 patients in each arm. The study group received 100 mg rectal diclofenac immediately after cesarean section followed by 50 mg at 12 hours and 100 mg at 36 hours after the surgery. The control group did not receive any diclofenac suppositories. RESULTS: The results showed that the visual analogue score for pain in the study group was significantly less at 12, 18 and 24 hours after surgery (P <0.05). The amount of pethidine consumed was also significantly less (P <0.05) with 28 injections consumed in the study group as compared with 52 in the control group (each pethidine injection = 100 mg). The incidence of sedation and constipation was significantly less (P<0.05) in the study group. However, the incidence of nausea and post-operative pyrexia was comparable in the 2 groups. CONCLUSION: Rectal diclofenac provides effective analgesia when given after cesarean section. It also reduces the patients opioid requirements with a corresponding reduction in the opioid related side-effects.

Administration, Rectal↗