P53 alterations in a group of Egyptian colorectal cancer patients

The p53 gene is located on human chromosome 17p13.1 and consists of 11 exons. Deficiencies in the p.53 gene can cause the cancerous cells to spread to distant organs. The most common p53 abnormalities that can lead to metastasis of colorectal tumours are mutation and deregulation of the gene. Aim of the study in the present study, we assessed the presence of P53 gene mutations and p53 protein expression and their prognostic significance in 43 patients with colorectal cancer. Histopathological examination of colonoscopic biopsies specimens, chest and abdomen CT were done for all patients. Genomic DNA was extracted, and exons 4-8 of the p53 gene were amplified, and analyzed for mutations by single strand conformation polymorphism [SSCP] and direct sequencing. The production of p53 proteins was studied by immunohistochemistry [IHC]. Results P53 mutations were found in 27/43 [63%] cases. A total of 11 types of p53 gene mutations were found by direct sequencing. More than half of these mutations appear in three hot spot codons: 175, 248 and 273. The SSCP analysis demonstrate that most common p53 gene alterations were found in exon 5 [35%]. IHC detected 34 tumors [79%] with protein overexpressior [when a cut point of 20% positive cells] and 25 tumours [58%] [When a cut point of >/= 50% positive cells were used]. it was found that p53 mutation analysis corresponds well with p53 immunohistochemistry [p < 0.001]. The majority of gene mutations were found in tumours from the rectum and distal colon. No statistical signitficant relation was found between P53 gene mutations and Duke's staging [P > 0.05]. However, a significant statistical relation was found between P53 gene mutations and prognosis in the studied colorectal cancer patients [p < 0.05]. Molecular and cellular evaluation. of p53 is clinically important, and there are strong indications, especially in colorectal cancer, that mutational status and mutational position in the P53 gene have a prognostic value. However the study of other genes involved in colorectal cancer is necessary

Endoscopic retrograde cholangiopancreatography in infants and children with cholestasis

Reports of ERCP in children are still limited. We present an experience with ERCP in 50 consecutive patients of the pediatric group. Children with obstructive jaundice indicated for ERCP are included in this study. ERCP was performed using the Olympus XPJ 230 in children older than one year, whereas in children less than one year old an Olympus PJF fiber duodenoscope was used. ERCP was able to diagnose 17 patients [34%] with choledochal cysts. Nine [18%] cases with choledocholithiasis either associated with hemolytic anemia or not were diagnosed and treated by ERCP [ES and stone extraction]. Fourteen cases with suspicion of EHBA were examined by ERCP and EHBA was diagnosed in 5 main out of 6 patients. In eight patients ERCP examination revealing normal biliary ductal system was very helpful and exploratory laparotomy to exclude EHBA was avoided. Two cases with parasitic worms obstructing the CBD were diagnosed by ERCP and treated also by ES and worm extraction by basket. Three cases of Caroli's disease [intrahepatic biliary radicles dilatation] were also diagnosed by ERCP and drainage of the IHBR also achieved by ES and internal biliary prosthesis placement in two of these patients. One case with sclerosing cholangitis was confirmed by ERCP. Biliary obstruction by thick inspissated bile was diagnosed and treated by ERCP in one case. Two postoperative obstruction of biliary system one case an old blocked stent was removed. The other case was diagnosed with ligated CBD and was sent back for revision of surgery. One case with congenital hepatic fibrosis and dilated IHBR on ultrasound was examined by ERCP which showed no IHBR dilatation and therefore excluding associated Caroli's disease. Only two cases with mild post ERCP, cholangitis and pancreatitis. ERCP is an important diagnostic modality in infants and children with cholestasis offering valuable detailed information on the biliary and pancreatic ductal system and it has the advantage over MRCP and CT in offering diagnostic as well as therapeutic capabilities, with very minimal complications

Clinical and molecular analysis of P53 gene mutation events in colorectal cancer patients

This study aimed to investigate the role of p53 gene mutations and deletion events in 46 patients with colorectal cancer [histologically diagnosed]. Immunohistochemistry and PCR/SSCP [polymerase chain reaction and single strand conformational polymorphism] were used to improve the accuracy of the currently used staging systems. P53 mutations were found in 25/46 cases. The majority of gene mutations were found in tumors from the left colon. There was no statistical relation between P53 gene mutations reported and Dukes staging. Meanwhile, there was a significant statistical relation between p53 gene mutations and the prognosis of the cases. The study showed that codon 175 was the most unstable one and that nucleotide mutation CGC to CAC was the commonest mutation form. The application of p53 mutation gene analysis may have clinical implications in colorectal cancer patients. However, the study of other genes involved in colorectal cancer is necessary

Efficacy of cystatin C as a screening test for reduced glomerular filtration rate

The objective of this study was to evaluate the efficacy of cystatin C as a screening test for reduced glomerular filtration rate [GFR] in comparison to S. creatinine and to assess whether cystatin C is performed differentially in either glomerular or tubular renal diseases or not. This study involved 105 patients with different renal diseases they were admitted as inpatients in Internal Medicine Department at Ain Shams University Hospital, and were classified according to GFR ml/min/1.73 m[2] into : group I patients, n = 35, GFR >/= 70 ml/min/1.73 m[2] group II patients, n = 33, GFR [< 70 - >/= 50] ml/mins/1.73m[2] and group III patients, n= 37, GFR < 50ml/min/1.73m[2], and a control group of 30 volunteers with matched age and sex to evaluate the reference value of cystatin C. All groups were subjected to the following : complete history taking and thorough clinical examination. Kidney function tests including : Bun, S. creatinine, creatinine clearance, 24 hours urinary proteins quantitation, [99m]Tc DTPA renal isotope scanning for accurate evaluation of glomerular filtration rate [GFR]. Abdominal U/S with full comment on the kidneys. Qualitative assessment of urinary proteins. Assessment of serum cystatin C by DAKO cystatin C pet kit which is particle enhanced turbidimetric immunassay. Our results revealed that the mean S. cystatin C was 7.9 +/- 3.8, 14.3 +/- 8.2 and 16.2 +/- 3.6 mg/l in groups I, II and III respectively when compared with that of the control group with a mean of 0.9 +/- 1 mg/l it was statically highly significant [F = 61.8, P < 0.01]. S. cystatin C was more sensitive than S. creatinine in reflecting the true GFR, this was specially observed in group I patients [mild renal impairment] as their mean serum creatinine was still within its normal range 0.97 +/- 0.4 mg/dl, while their mean GFR measured by both creatinine clearance and isotope clearance was 68.3 +/- 4.7, 67.5 +/- 45 ml/min/1.73 m[2] respectively. Meanwhile, their mean S. cystatin C was 7.9 +/- 3.8 mg/l statistically highly significant than that of the control group with a mean of 0.9 +/- 1 mg/l, [P < 0.05]. Also there was statistically non significant correlation between S. cystatin C and S. creatinine in group I patients [r = 0.1, P > 0.05] while there was significant correlation between them in group II and III patients [r = 0.38, 0.59, P < 0.05]. Moreover, S. cystatin C has a significant negative correlation with GFR measured by both creatinine clearance [r = -0.37, -0.54 and -0.48] and radioisotope clearance [r = -0.34, -0.35 and -0.37], [P < 0.05] in groups I, II and III respectively, i.e., throughout the whole range of renal impairment. Cystatin C had non significant correlation with either age or sex of the patients. While, S. creatinine had a significant correlation with creatinine clearance and isotope clearance in group II and III patients, i.e., with advanced renal diseases, but not with group I patients [mild renal impairment]. Also S. cystatin C had higher sensitivity [90% [vs] 83%] and negative predictive value [NPV] [89 [vs] 80] than S. creatinine in assessing GFR measured by both creatinine clearance or by radioisotope clearance. There was non significant difference regarding the mean S. cystatin C between subgroup [A] [glomerular diseases] and subgroup [B] [tubular diseases] within the same GFR category [P > 0.05]. S. cystatin C was more sensitive and superior to S. creatinine in detecting reduced GFR measured by both creatinine and radioisotope clearance. S. cystatin C is more efficacious than S. creatinine as a screening test as it had a higher sensitivity and higher negative predictive values than S. creatinine. In detecting reduced GFR. The efficacy of cystatin C is independent on either glomerular or tubular renal diseases and showed a high degree of reproducibility

Neuropeptide Y: a modulator of apoptosis in systemic lupus erythematosus

Systemic lupus erythematosus [SLE] is a multisystem disease characterized by the production of pathological autoantibodies and altered humoral and cellular immune responses. The death receptor Fas is known to induce apoptosis upon interaction with its ligand with consequent activation of caspases and is reported to have an important role in the pathogenesis of SLE. Recently, it has been reported that the nervous system interacts with and directly modulates the immune response through the production of certain neuropeptides as neuropeptide Y [NPY]. To assess the serum level of NPY in SLE patients and to investigate its correlation with the activity of the disease, the level of Fas expression on mononuclear cells and the incidence of apoptosis in SLE patients. The study was conducted on 20 SLE patients and 10 healthy controls. Fas expression was assessed with flow cytometry using mouse antihuman FITC conjugated anti-CD95. The% of apoptotic cells was assessed after cell culture with flow cytometry using propidium iodide staining. NPY was assessed with competitive radioimmunoassay kit for both patients and controls. Both Fas and NPY levels were found to be significantly elevated in SLE as compared with healthy controls [p< 0.01]. Moreover, both levels were found to correlate significantly with the activity score of the disease and with each other. However, despite the elevated Fas expression, the% of apoptotic cells are not significantly increased in SLE compared to healthy controls. Fas expression could be considered a marker of lymphocyte activation in SLE. The presence of high levels of neuropeptides as NPY reflects the link between nervous and immune system. NPY could play an important role as endogenous modulator of the immune response in SLE probably through their inhibiting effect on Fas ligand expression and so switch the lymphocytes to an apoptosis resistant phenotype, which could lead to the activation of autoreactive cells. Thus neuropeptide Y may play an important role in the pathogenesis of SLE

Study of the impact of some hormones on brith weight

The aim of the present work was to study the relationship of neonatal leptin, insulin and human placental lactogen [hPL] to birth weight, gender difference and the maternal levels. Serum leptin, insulin and hPL were assessed in the cord blood of 60 neonates and the venous blood of their mothers. The neonates were classified according to their birth weight into 23 appropriate for gestational age [AGA] 20 large for gestational age [LGA] and 17 small for gestational age [SGA]. Data showed insignificant correlation of maternal hPL with insulin and leptin in both maternal and neonatal samples. Neonatal leptin, insulin and maternal hPL are important hormones that regulate the fetal growth and development. Insulin and leptin levels were significantly higher in the maternal blood than in the cord blood. Moreover, insignificant correlation was found regarding both hormones in the two compartments. Neonatal leptin and insulin showed no gender difference in neonates of different birth weights. The association of neonatal leptin or insulin with birth weight and the significant positive correlation between both are the determinative factors for the fetal birth weight

Computed tomography of the abnormal sella: Correlation with clinical and hormonal findings

Computed tomography [CT] findings are presented in four groups of 37 patients, all of whom had evidence of an abnormal sella. Of the group of 14 patients with a pituitary tumour, 7 had hormonal studies available and all of these correlated with the CT diagnosis. In the group of 17 cases suspected of having an empty sella, the initial CT established the diagnosis conclusively in 11. Of the remaining 6, the diagnosis of empty sella was confirmed by CT with metrizamide cisternography in 4 cases, whilst the diagnosis remained uncertain in 2 patients who did not return for further investigation. The third group comprised 6 patients who were being followed up after surgical removal of pituitary adenoma, and two of these showed radiological evidence of recurrence supporting clinical and hormonal findings. In the last group of 2 patients, the sellar abnormalities remained undefined as they did not return for further investigation. In all 21 patients who had hormonal assays available in this series, the findings correlated diagnostically with those of CT