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Biomedical subjects

M M Ahmed

Publications and source records attributed to M M Ahmed.

At least 19 recordsLinked to original sources

Thyroid dysfunction and thyroid autoimmunity in Saudi type 2 diabetics.

Diabetes mellitus and thyroid disease are common endocrine disorders in the general population. To investigate the association between thyroid dysfunction, thyroid autoimmunity and Saudi type 2 diabetics, a random sample of 100 Saudi type 2 diabetics and 100 age- and sex-matched controls were studied. The mean age was 54 years for diabetics and 55 years for controls while the male:female ratios were 1:1.6 and 1:14 respectively. GAD65ab were found in 26% diabetics and 2% controls (p=0.001). Thyroid autoimmunity were detected in 10% diabetics vs. 5% controls (p=0.05), while thyroid dysfunction was found in 16% and 7% respectively (p=0.03). In GAD65ab-positive diabetics, thyroid autoimmunity was observed in 27% vs. 4% GAD65ab-negative diabetics (p=0.02) and thyroid dysfunction was reported in 42% and 7% respectively. We conclude that thyroid dysfunction and autoimmunity are common in Saudi type 2 diabetics. Further studies are needed on the cost effectiveness of thyroid screening in diabetics.

Autoimmunity↗

Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis in 2 patients with end-stage renal disease on hemodialysis.

Nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis (NFD/NSF) is a newly recognized disorder occurring in patients with renal failure. It is manifested by progressive cutaneous and systemic fibrosis involving the extremities and the trunk with usual sparing of the face and internal organs. NFD/NSF can lead to joint contractures and painful disability. The etiology is unknown and there are no proven effective treatments. NFD/NSF must be distinguished from other clinically similar disorders such as scleroderma, scleromyxedema, and eosinophilic fasciitis among a myriad of others. NFD/NSF can pose many diagnostic challenges to physicians; however, a team of experienced rheumatologists, nephrologists, dermatologists, and dermatopathologists is essential in identifying this disorder. We report 2 new cases of NFD/NSF in patients on hemodialysis.

Adult↗

Metallic stents in large bowel obstruction: experience in a District General Hospital.

INTRODUCTION: Metallic stents are used increasingly in the palliation of malignant large bowel obstruction. Stenting has also been used in the setting of acute obstruction, allowing appropriate patient preparation for an elective colectomy. METHODS: Uncovered metallic stents were inserted using a combined endoscopic/radiological technique in patients presenting with large bowel obstruction. RESULTS: Seventeen patients (10 female, mean age 75.2 years) presented with large bowel obstruction, 14 due to malignancy and 3 secondary to diverticular stricture. Technical success was achieved in 13/17 with clinical success in 12 of these 13. There were no perforations or procedure related deaths. One stented patient had elective surgery. The five patients with clinical/technical failure required emergency surgery. CONCLUSION: The result of our preliminary experience in the use of metallic stents is encouraging. Metallic stents should be available in all hospitals as part of a multimodality approach in treating large bowel obstruction.

Adult↗

Genetic haemochromatosis presenting as porphyria cutanea tarda.

Porphyria cutanea tarda (PCT) is the commonest form of porphyria. It can be inherited or acquired. We present a case of genetic haemochromatosis with associated PCT. Venesection led to improvement in both conditions. We highlight the need for the awareness of PCT and its associated conditions.

Aged↗

Effect of memantine on the levels of glial cells, neuropeptides, and peptide-degrading enzymes in rat brain regions of ibotenic acid-treated alzheimer's disease model.

It has been implicated that glia activation plays a critical role in the progression of Alzheimer's disease (AD). However, the precise mechanism of glia activation is not clearly understood yet. In our present studies, we confirmed our previous results where change the levels of neuropeptides and peptidases in ibotenic acid (IBO) infusion into the rat nucleus basalis magnocellularis, an animal model of AD. Furthermore, we extended our study to investigate a possible protection effect of co-administration on the changes of neuropeptides, and neuronal and glial cells in IBO-infused rat brain by memantine treatment. The levels of substance P and somatostatin were decreased in the striatum and frontal cortex 1 week after IBO infusion, and recovered to the control level by memantine treatment, indicating the involvement of neuropeptides in AD pathology. Furthermore, the immunohistochemical and enzymatic studies of GFAP and CD 11b, and peptidylarginine deiminase, markers of glia, in the striatum and frontal cortex showed the increase in IBO-treated rat brain as compared with controls, while co-administration of memantine and IBO no increase of astrocytes and microglia activation was observed. The present biochemical and immunohistochemical results suggest that glia activation might play an important role to the pathology of AD, and correlate with the changes of neuropeptide levels in AD brain that is recovered by memantine treatment.

Alzheimer Disease↗

Esophageal involvement in cicatricial pemphigoid: a rare cause of dysphagia.

Cicatricial pemphigoid is a rare, autoimmune, blistering disorder affecting the mucous membranes and skin. Esophageal involvement affects a small proportion of affected individuals and may present up to 10 years after the initial onset of the disease. We present a case of esophageal cicatricial pemphigoid that presented initially as linear IgA disease. We describe the successful treatment of dysphagia by graded esophageal dilatations.

Deglutition Disorders↗

Effects of Taxol plus radiation on the apoptotic and mitotic indices of mouse intestinal crypt cells.

PURPOSE: In this study we investigated the effect of Taxol, radiation, or Taxol plus radiation on highly proliferative normal tissue--the intestinal crypt cells of Swiss albino mice. MATERIALS AND METHODS: Swiss-albino mice, 3-4 months old, were used in this study. Taxol was administered by bolus intravenously through the tail vein. Radiation was given using a linear accelerator. There were four treatment categories, which comprised a total of 34 groups. Each group consisted of five animals. The first category was a control category which comprised one group (n = 5). The second treatment category was Taxol alone which comprised three groups (n = 15). The third treatment category was radiation alone which comprised three groups (n = 15). The fourth treatment category was Taxol plus radiation which comprised 27 groups (n = 135). Mice were killed 24 h after Taxol or radiation or combined administration using ether anesthesia. Using a light microscope, apoptotic and mitotic indices were counted on jejunal crypt cells of mice that were stained with hematoxylin-eosin. Differences between groups were statistically evaluated with Student's t-test. RESULTS: Taxol caused a dose-dependent increase in apoptosis (P = 0.045) and decreased the mitotic index (P = 0.006) at high doses. Similarly, radiation caused a dose-dependent increase in apoptosis (P = 0.046) and decreased the mitotic index (P = 0.299) at higher radiation doses. Compared to radiation alone, Taxol caused a significant induction of apoptosis (P = 0.010). In combination, no significant radiosensitizing effect of Taxol was observed (enhancement ratio < 1), when compared to radiation alone. However, an increase in apoptosis was observed after 24 h of Taxol exposure when compared to 12 or 48 h of Taxol exposure (P = 0.0001 and P = 0.0001). CONCLUSION: These findings suggest that Taxol did not cause a radiosensitizing effect in intestinal crypt cells. However, a 24-hour pretreatment of Taxol exposure followed by radiation caused significant induction of apoptosis and reduction of the mitotic index when compared to other Taxol timing sequences. Thus, the lack of a radiosensitizing effect of Taxol in these proliferative cells may be due to enhanced mitotic death rather than apoptotic death.

Animals↗

Adsorptive stripping voltammetric determination of antihypertensive agent: diltiazem.

Adsorptive stripping voltammetry was used to determine the antihypertensive agent diltiazem in phosphate buffer (pH 7.0). The adsorptive cathodic peak was observed at -1.72 V vs. Ag/AgCl. The peak response was characterized with respect to pH, preconcentration time, possible interferences, accumulation potential and supporting electrolytes. The obtained results were analyzed and the statistical parameters were calculated. The proposed method was applied to determine the mentioned drug in pharmaceutical formulation (capsule) and urine. The detection limit is 1x10(-8) M (4.5 ng ml(-1)) using 180 s preconcentration time, whereas the lower limit of detection is 6x10(-9) M (2.7 ng ml(-1)).

Antihypertensive Agents↗

Fate of postharvest-applied dichlorvos in stored and processed dates.

The fate of dichlorvos (DDVP) on dates after storage and processing of postharvest-treated fruits has been investigated. Residues were determined using GC-ECD after extraction of the fruits. A postharvest application was made to fruits at different stages of maturity: khalal fruits (mature full colored stage), rutab fruits (soft brown stage), and the mature tamer fruits (hard raisin-like stage). The fate of the residues was followed during the storage at refrigerated, room, and summer average temperatures (3, 22, and 43 degrees C). The amount of residues absorbed varied with the level of maturity. The rate of the loss of the residues was found to follow first-order kinetics. First-order rate constants were calculated for the different levels of maturity. The rate of the loss of DDVP increased as the temperature of storage increased. Also, it decreased with increasing maturation of the dates, which was characterized by a decrease in moisture content as well as water activity and an increase in sugar content. The period of storage study was limited by the time of maturation to the next stage. Most common home-cooking methods, including dehydration, jam-making, and syrup-making, resulted in significant decreases in residue levels. Only 0-13% of initial DDVP residues was detected in final products.

Chromatography, Gas↗

Early growth response-1 gene: potential radiation response gene marker in prostate cancer.

This study was undertaken to determine whether the transcription factor EGR-1 expression: (1) in the primary tumor, correlates with radiation response in terms of complete local tumor control with no evidence of disease or recurrence and no evidence of metastasis; (2) in the postirradiated biopsies correlates with residual tumor; and (3) correlates with the expression of Egr-1 target genes such as TP53, pRB, and Bax. The authors analyzed: (1) 25 pretreated surgically resected paraffin-embedded primary adenocarcinomas of the prostate for the presence of EGR-1 expression and mutation, and correlated this with clinical endpoints such as serum prostate-specific antigen levels and current clinical status; (2) 27 postirradiated biopsies of prostate for the presence of EGR-1 expression, and correlated these findings to the residual tumor status; and (3) 12 prospective prostate tumor specimens for EGR-1 expression and its target genes. EGR-1 expression was determined by immunohistochemistry and mutations were screened in two regions of the Egr-1 gene (trinucleotide AGC repeats in transactivation domain [TD] and poly A tract in 3'UTR) by polymerase chain reaction-single strand conformational polymorphism analysis. Of 25 patients, 18 patients showed expression of EGR-1. EGR-1 overexpression correlated with treatment failure. No correlation with EGR-1 overexpression and its target genes was found, which may indirectly suggest that overexpressed EGR-1 may lack transactivation function. In summary, EGR-1 overexpression in the mutant form may provide an indication of clinical failure (local recurrence or metastasis).

Adenocarcinoma↗

Low dose fractionated radiation enhances the radiosensitization effect of paclitaxel in colorectal tumor cells with mutant p53.

BACKGROUND: The current study was undertaken to investigate the influence of wild-type or mutant p53 status on the radiosensitizing effect of paclitaxel in colorectal tumor cell lines. METHODS: HCT-116 (contains wild-type p53) and HT-29 (contains mutant p53) established from moderately differentiated colorectal carcinomas were used in this study. Colony-forming assay was performed after exposure to either different radiation doses (0.5-6 gray [Gy]) or paclitaxel (1-10 nM) or in combination. Induction of p53 and p21(waf1/cip1) by these treatments were determined by immunocytochemistry and Western blot analysis. RESULTS: Radiation caused an increase in nuclear p53 and p21(waf1/cip1) proteins in HCT-116 cells, indicating that p53 functionally induced p21(waf1/cip1). However, induction of nuclear p53 and p21(waf1/cip1) protein was not evident in HT-29 cells, suggesting that p53 was not functional in these cells. Survival data showed that the HCT-116 cells (survival fraction of exponentially growing cells that were irradiated at the clinically relevant dose of 2 Gy [SF(2)] = 0.383; dose required to reduce the fraction of cells to 37% [D(0)] = 223 centigray [cGy]) were significantly sensitive to ionizing radiation (P < 0.008) when compared with the HT-29 cells (SF(2) = 0.614; D(0) = 351 cGy). Paclitaxel caused a higher degree of clonogenic inhibition in HCT-116 (D(0) = 0.7 nM) than HT-29 (D(0) = 1.11 nM) cells (P < 0.06). When paclitaxel and radiation were combined, an enhanced radiosensitizing effect (P < 0.05) was observed in HCT-116 cells (SF(2) = 0.138; D(0) = 103 cGy), whereas in HT-29 cells no significant radiosensitization of paclitaxel was observed (SF(2) = 0.608; D(0) = 306 cGy). However, pretreatment with paclitaxel followed by multifractionated low dose radiation (0.5- or 1-Gy fractions for a total dose of 2 Gy) significantly enhanced the radiosensitizing effect in both HCT-116 and HT-29 cells. CONCLUSIONS: The results of the current study suggested that multifractionated radiation given at very low doses after exposure of cells to paclitaxel conferred a potent radiation sensitizing effect irrespective of p53 status.

Antineoplastic Agents, Phytogenic↗

Ionizing radiation down-regulates p53 protein in primary Egr-1-/- mouse embryonic fibroblast cells causing enhanced resistance to apoptosis.

In this study, we sought to investigate the mechanism of the proapoptotic function of Egr-1 in relation to p53 status in normal isogenic cell backgrounds by using primary MEF cells established from homozygous (Egr-1(-/-)) and heterozygous (Egr-1(+/-)) Egr-1 knock-out mice. Ionizing radiation caused significantly enhanced apoptosis in Egr-1(+/-) cells (22.8%; p < 0.0001) when compared with Egr-1(-/-) cells (3.5%). Radiation elevated p53 protein in Egr-1(+/-) cells in 3-6 h. However, in Egr-1(-/-) cells, the p53 protein was down-regulated 1 h after radiation and was completely degraded at the later time points. Radiation elevated the p53-CAT activity in Egr-1(+/-) cells but not in Egr-1(-/-) cells. Interestingly, transient overexpression of EGR-1 in p53(-/-) MEF cells caused marginal induction of radiation-induced apoptosis when compared with p53(+/+) MEF cells. Together, these results indicate that Egr-1 may transregulate p53, and both EGR-1 and p53 functions are essential to mediate radiation-induced apoptosis. Rb, an Egr-1 target gene, forms a trimeric complex with p53 and MDM2 to prevent MDM2-mediated p53 degradation. Low levels of Rb including hypophosphorylated forms were observed in Egr-1(-/-) MEF cells before and after radiation when compared with the levels observed in Egr-1(+/-) cells. Elevated amounts of the p53-MDM2 complex and low amounts of Rb-MDM-2 complex were observed in Egr-1(-/-) cells after radiation. Because of a reduction in Rb binding to MDM2 and an increase in MDM2 binding with p53, p53 is directly degraded by MDM2, and this leads to inactivation of the p53-mediated apoptotic pathway in Egr-1(-/-) MEF cells. Thus, the proapoptotic function of Egr-1 may involve the mediation of Rb protein that is essential to overcome the antiapoptotic function of MDM2 on p53.

Adaptor Proteins, Signal Transducing↗

Characterization of a newly established human pancreatic carcinoma cell line, UK Pan-1.

BACKGROUND: A highly tumorigenic cell line designated as UK Pan-1 was established in a surgically removed human pancreatic adenocarcinoma and characterized as having many of the genotypic and phenotypic alterations commonly found in pancreatic tumors. METHODS: The cell line was characterized by its morphology, growth rate in monolayer culture and soft agar, tumorigenicity in nude mice, and chromosomal analysis. Furthermore, the status of p53, Ki-ras mutation and transforming growth factor (TGF)-/receptor expression were determined. The characteristics of UK Pan-1 were compared with those of other commonly used pancreatic carcinoma cell lines. RESULTS: Quiescent UK Pan-1 cells could be stimulated to proliferate in growth factor free nutrient media, indicating a growth factor independent phenotype. UK Pan- 1 cells grew in soft agar and rapidly formed tumors in nude mice. This cell line possesses a mutation at codon 12 of the c-Ki-ras-2 gene that is commonly found in pancreatic carcinoma. Fluorescence in situ hybridization showed that two alleles of p53 tumor suppressor gene were present in UK Pan-1. However, sequencing analysis revealed a mutation in one allele at exon 8, codon 273 (G to A; Arg to His). Additional growth assays indicated that the cell line was insensitive to negative growth regulation induced by exogenous TGF-beta. Molecular analysis of the TGF-beta signaling pathway showed that UK Pan-1 did not express appreciable levels of the TGF-beta receptor type I, II, or III mRNAs, but did express DPC4 mRNA. Karyotype analysis revealed an 18q21 deletion indicating a possible loss of heterozygosity for DPC4, as well as other chromosomal deletions and rearrangements. CONCLUSIONS: This study indicates that UK Pan-1 is a highly tumorigenic cell line possessing a molecularly complex pattern of mutations that may be used as a model to further the understanding of the mechanisms responsible for the development of pancreatic carcinoma.

Adenocarcinoma↗

Deep vein thrombosis at King Abdul Aziz University Hospital.

OBJECTIVE: To study the incidence of deep vein thrombosis and pulmonary embolism at King Abdul Aziz University Hospital. To determine the risk factors, use of different diagnostic modalities, treatment given and to compare our findings with those reported in the literature. METHODS: Retrospective study which included all cases of deep vein thrombosis and pulmonary embolism admitted to the medical ward of King Abdul Aziz University Hospital during the period between January 1994 till March 1999 were analyzed. RESULTS: Total of 75 patients were diagnosed to have deep vein thrombosis with mean age of 44.16 +/- 14.5 years and male:female ratio of 1:2. Doppler ultrasound was used for the diagnosis in 56 of 75 patients (75%). Pulmonary embolism as a complication of deep vein thrombosis developed in 24 of 75 patients (32%). Prolonged immobilization was found to be the most common risk factor 17 of 75 (23%). All the patients were treated with conventional heparin followed by warfarin. CONCLUSION: As discussed, our results are comparable with those reported in the literature. Post operative patients who are anticipated to have prolonged immobilization should receive prophylactic anti coagulation with subcutaneous heparin. Thrombophillia screening should be reserved for those with recurrent deep vein thrombosis or patients with positive family history.

Adult↗

High-dose spatially-fractionated radiation (GRID): a new paradigm in the management of advanced cancers.

PURPOSE: With the advent of megavoltage radiation, the concept of spatially-fractionated (SFR) radiation has been abandoned for the last several decades; yet, historically, it has been proven to be safe and effective in delivering large cumulative doses (> 100 Gy) of radiation in the treatment of cancer. SFR radiation has been adapted to megavoltage beams using a specially constructed grid. This study evaluates the toxicity and effectiveness of this approach in treatment of advanced and bulky cancers. METHODS AND MATERIALS: From January 1995 through March 1998, 71 patients with advanced bulky tumors (tumor sizes > 8 cm) were treated with SFR high-dose external beam megavoltage radiation using a GRID technique. Sixteen patients received GRID treatments to multiple sites and a total of 87 sites were irradiated. A 50:50 GRID (open to closed area) was utilized, and a single dose of 1,000-2,000 cGy (median 1,500 cGy) to Dmax was delivered utilizing 6 MV photons. Sixty-three patients received high-dose GRID therapy for palliation (pain, mass, bleeding, or dyspnea). In 8 patients, GRID therapy was given as part of a definitive treatment combined with conventionally-fractionated external beam irradiation (dose range 5,000-7,000 cGy) followed by subsequent surgery. Forty-seven patients were treated with GRID radiation followed by additional fractionated external beam irradiation, and 14 patients were treated with GRID alone. Thirty-one treatments were delivered to the abdomen and pelvis, 30 to the head and neck region, 15 to the thorax, and 11 to the extremities. RESULTS: For palliative treatments, a 78% response rate was observed for pain, including a complete response (CR) of 19.5%, and a partial response (PR) of 58.5% in these large bulky tumors. A 72.5% response rate was observed for mass effect (CR 14.6%, PR 52.9%). The response rate observed for bleeding was 100% (50% CR, 50% PR) and for dyspnea, a 60% PR rate only. A relatively higher response rate (CR 23.3%, PR 60%) was observed in patients who received GRID treatment in the head and neck area. No grade 3 late skin, subcutaneous, mucosal, GI, or CNS complications were observed in any patient in spite of these high doses. In the 8 patients who received GRID treatment for definitive treatment, a clinical CR was observed in 5 patients (62.5%) and a pathological complete response was confirmed in the operative specimen in 4 patients (50%). CONCLUSION: The efficacy and safety of using a large fraction of SFR radiation was confirmed by this study and substantiates our earlier results. In selected patients with bulky tumors (> 8 cm), SFR radiation can be combined with fractionated external beam irradiation to yield improved local control of disease, both for palliation and selective definitive treatment, especially where conventional treatment alone has a limited chance of success.

Dose Fractionation, Radiation↗

Hepatitis C viral load, genotype and histological severity in patients with bleeding disorders.

We report the relationship between hepatitis C virus (HCV) titre, liver histology and HCV genotype in patients with bleeding disorders. One hundred and thirty-two RIBA-2-positive patients, including 56 who were also HIV positive, were identified at our centre. Fifty of these patients, including nine who were HIV infected, underwent percutaneous liver biopsy. Liver histology was assessed using a modified histological activity index (HAI). Qualitative serum HCV PCR was positive in 87 (87%) of the 101 patients tested including 43 of 50 biopsied patients. HCV RNA titres, measured by quantitative PCR, were significantly higher in HIV-positive patients compared with HIV-negative patients (P < 0.05) but were not related to HAI, mean factor concentrate usage, duration of HCV infection or HCV genotype. There was no relationship between HCV genotype and HAI. Qualitative HCV PCR was positive in 30 of 43 liver biopsies tested. Biopsy PCR-positive and -negative cohorts were not distinguished by HAI or serum HCV titre. We conclude that although serum HCV PCR is useful in confirming the presence of HCV infection in patients with bleeding disorders, little meaningful information concerning the severity of the disease can be obtained from serum HCV quantification.

Adult↗

Long-term stability of anterior segmental maxillary osteotomy.

The long-term stability of anterior segmental maxillary osteotomy was evaluated in 11 patients. Both the Wunderer and down-fracture procedures were used. The patients were examined periodically until 18 months after surgery. Operative and postoperative cephalograms were compared; a more reliable method was utilized to assess the displacement of the osteotomy segment. Linear and angular measurements were used for evaluation of relapse. No major complications were recorded, and no correlation was found between the magnitude of segment repositioning and degree of relapse. Positional changes at the end of the study, though statistically significant, were clinically acceptable and subjectively undetectable. Results emphasized the merits and potential of the surgical osteotomy. Satisfactory correction of anterior maxillary excess was achieved, with absolute improvement in esthetics and occlusion.

Adult↗