Effect of BRAF mutational status on expression profiles in conventional papillary thyroid carcinomas.

BACKGROUND: Whereas 40 % to 70 % of papillary thyroid carcinomas (PTCs) are characterized by a BRAF mutation (BRAFmut), unified biomarkers for the genetically heterogeneous group of BRAF wild type (BRAFwt) PTCs are not established yet. Using state-of-the-art technology we compared RNA expression profiles between conventional BRAFwt and BRAFmut PTCs. METHODS: Microarrays covering 36,079 reference sequences were used to generate whole transcript expression profiles in 11 BRAFwt PTCs including five micro PTCs, 14 BRAFmut PTCs, and 7 normal thyroid specimens. A p-value with a false discovery rate (FDR) < 0.05 and a fold change > 2 were used as a threshold of significance for differential expression. Network and pathway utilities were employed to interpret significance of expression data. BRAF mutational status was established by direct sequencing the hotspot region of exon 15. RESULTS: We identified 237 annotated genes that were significantly differentially expressed between BRAFwt and BRAFmut PTCs. Of these, 110 genes were down- and 127 were upregulated in BRAFwt compared to BRAFmut PTCs. A number of molecules involved in thyroid hormone metabolism including thyroid peroxidase (TPO) were differentially expressed between both groups. Among cancer-associated molecules were ERBB3 that was downregulated and ERBB4 that was upregulated in BRAFwt PTCs. Two microRNAs were significantly differentially expressed of which miR492 bears predicted functions relevant to thyroid-specific molecules. The protein kinase A (PKA) and the G protein-coupled receptor pathways were identified as significantly related signaling cascades to the gene set of 237 genes. Furthermore, a network of interacting molecules was predicted on basis of the differentially expressed gene set. CONCLUSIONS: The expression study focusing on affected genes that are differentially expressed between BRAFwt and BRAFmut conventional PTCs identified a number of molecules which are connected in a network and affect important canonical pathways. The identified gene set adds to our understanding of the tumor biology of BRAFwt and BRAFmut PTCs and contains genes/biomarkers of interest.

Effect of thawing rate and post-thaw culture on the cryopreserved fetal rat islets: functional and morphological correlation.

The ability of the fetal pancreatic islet cells to multiply rendered them a potential tissue for transplantation studies to cure diabetes. A bank of fetal islets could be created with proper storage in liquid nitrogen. The aim of this study is to evaluate the effect of thawing rate and post-thaw culture on the structural and functional integrity of isolated cryopreserved islets of rat fetuses. Fetal rat islets were isolated by the collagenase digestion, cultured for three days, and then cryopreserved using dimethylsulphoxide as cryoprotectant and the step-rate cooling to -40 degrees C before immersing them in liquid nitrogen. The islets were thawed by the slow or fast warming rates using hyperosmolar sucrose solution and then cultured for 1 or 2 days. Insulin and C-peptide contents of the slow thawed islets were higher than those of the control. In the fast thawed islets the contents were similar to those of the control. Insulin and C-peptide release in response to glucose for the slow thawed islets were lower than those of the control and in the fast thawed islets they were similar to that of the control. Histological examination showed irregular periphery and fragmented central part of the large slowly thawed islets, which showed also variable immunohistochemical reaction to anti-insulin serum, ranging from strongly positive reaction to markedly weak reaction. Fast thawed islets showed mostly regular periphery and their reaction to the anti-insulin serum was slightly weaker than that of the control islets. It was concluded that fast thawing and post-thaw culture is much better than slow thawing, as indicated by nearly normal insulin and C-peptide content and release and intact structural integrity.

Delayed presentation of traumatic diaphragmatic rupture.

We present a case of traumatic diaphragmatic rupture that presented two years after the initial thoracic injury. The patient presented with intestinal obstruction and colonic perforations. Through laparotomy, the diaphragmatic defect was repaired and the colonic perforations were closed. The patient had an uneventful post-operative recovery.

Wandering spleen.

Congenital malformations of the spleen are rare. We report 3 cases of wandering spleen presented as abdominal or pelvi-abdominal mass. Two patients were suffering from chronic lower abdominal pain with thrombosed splenic pedicle and the third patient had an acute abdomen. All patients underwent splenectomies. Abdominal ultrasound, computerized tomography, Doppler ultrasound, and radioisotope studies were used to confirm the diagnosis. The clinical, diagnostic and treatment modalities are discussed.

Structural study on cultured isolated fetal rat pancreatic islets.

OBJECTIVE: To perform a morphometric and structural study of the cultured isolated fetal rat pancreatic islets. METHODS: Islets of the fetal rat pancreas, aged 22 days were isolated by the standard procedure of collagenase digestion and culture technique. The islets were cultured for 1, 2, 3, 4 and 5 days. The islets were counted under a dissecting microscope and islet diameter and purity were measured under a phase contrast microscope fitted with a calibrated grid. The islet specimens were fixed in buffered neutral formalin, dehydrated in alcohol and embedded in parablast. Sections were stained with hematoxylin and eosin. This study was conducted in King Fahd Medical Research Center, Faculty of Medicine, King Abdul-Aziz University, Kingdom of Saudi Arabia, during 2003 and 2004. RESULTS: The purity of the cultured islets gradually increased with time and was significantly different between the cultured groups. The number of the cultured islets gradually decreased with time. The islet diameter gradually increased with culture period. The islet purity and diameter were significantly different between the cultured groups. Parablast sections stained with hematoxylin and eosin showed that the shape and histological structure of the cultured islets were intact. CONCLUSION: The results of the present work represent an extensive morphometric structural study of isolated cultured fetal islets. The culture islet diameter and purity showed gradual increase with culture period, while the islet number showed gradual decrease.

Spontaneous rupture of hepatocellular carcinoma.

Hepatocellular carcinoma is the most common malignancy among males and the 7th among female patients in the Kingdom of Saudi Arabia. This is due to the endemicity of hepatitis B and hepatitis C. Spontaneous rupture of hepatocellular carcinoma is rare. We report 4 cases of spontaneous rupture of hepatocellular carcinoma. Initial control of bleeding was achieved surgically in 3 patients and by embolization in the 4th patient. All patients had very good hepatic reserve as reflected by Child-Pugh scoring (A & B). We found that the incidence of ruptured hepatocellular carcinoma among 85 patients was 4.7%. The prognosis of this subgroup of patients is poor as reflected by the low median survival ranging from 6-16 weeks.

Sympathetic chain Schwannoma.

Schwannomas are rare, benign, slowly growing tumors arising from Schwann cells that line nerve sheaths. Schwannomas arising from the cervical sympathetic chain are extremely rare. Here, we report a case of a 70-year-old man who presented with only an asymptomatic neck mass. Physical examination revealed a left sided Horner syndrome and a neck mass with transmitted pulsation and anterior displacement of the common carotid artery. Computed tomography (CT) showed a well-defined non- enhancing mass with vascular displacement. The nerve of origin of this encapsulated tumor was the sympathetic chain. The tumor was excised completely intact. The pathologic diagnosis was Schwannoma (Antoni type A and Antoni type B). The patient has been well and free of tumor recurrence for 14 months with persistence of asymptomatic left sided Horner syndrome. The clinical, radiological and pathological evaluations, therapy and postoperative complications of this tumor are discussed.

Comparison of students' performance in the traditional oral clinical examination and the objective structured clinical examination.

OBJECTIVE: To find out whether the objective structured clinical examination (OSCE) using standardized patients allows the same evaluation of students as the traditional oral clinical examination (TOCE) using real patients. METHODS: The results of 4 cohorts of students (904 students) in the end of posting examination (using the TOCE), and the end of year examination (using OSCE) during the academic years 2003-2006 at King Abdulaziz University, Faculty of Medicine, Jeddah, Kingdom of saudi Arabia were analyzed retrospectively. Spearman's correlation coefficient was calculated for comparison of performance in the different parts of the 2 examinations. RESULTS: There was a strong positive correlation between the results of the OSCE and the final grade of the students (r=0.786), and between the TOCE and the final grade of the students (r=0.591). The coefficient for correlation between the results of the OSCE and TOCE was 0.406. CONCLUSION: The OSCE can be used for the evaluation of clinical skills like the TOCE with better objectivity and reliability.

Mediastinal parathyroid adenoma.

We present two cases that developed clinical, biochemical and radiological evidences of primary and secondary hyperparathyroidism. In the first case the adenoma was removed through a transcervical incision and in the second case the supernumerary adenoma was removed through sternotomy. Post operatively, patients had normal serum calcium and iPTH with complete disappearance of symptoms.

Hepatocellular carcinoma with cutaneous metastasis.

We report a 60-year-old male patient with hepatocellular carcinoma HCC who presented with cutaneous metastasis of the chest wall and ribs destruction. The tumor was advanced, and the patient died next day.