Mutational analyses of K-ras exon 2 in Thailand colorectal cancer tissue samples.

Objective: The main purpose of this study was to elucidate the genotype of K-ras gene in Thailand colorectal cancer tissue samples, especially in exon 2, which has never before been reported. Methods: 106 patients’ samples in formalin fixed paraffin embedded tissue blocks were investigated in this study. DNA was extracted and PCR was performed by using primers specific for the K-ras gene at exon 2. Direct sequencing was performed in a Genetic Analyser ABI3130 with specific software. Results: The mutation of K-ras exon 2 gene in Thailand colorectal cancer samples accounted for 37.7% of the total. The most common mutation found in this series was the G"A transition which accounted for 70%. Conclusion: The incidence of K-ras exon 2 mutation in Thailand colorectal cancer samples was remarkedly similar to previous reports.

Accuracy of multi-detector CT scan in pre-operative staging of renal cell carcinoma: Comparison of radiological and histopathological findings.

Objective: To evaluate the accuracy of pre-operative multi-detector CT scan (MDCT) compared to histopathology findings in tumor staging of renal cell carcinoma. Methods: Retrospective review of 29 renal cell carcinomas at Siriraj Hospital from 2004-2007. Two blinded radiologists evaluated the pre-operative MDCT images independently. Imaging findings were compared with surgical specimens and pathological findings. Results: A total of 29 renal cell carcinomas were proven on histopathology. The respective accuracy for overall staging of reader 1 and 2 were 0.75 and 0.65. The reader 1 and 2 reached a sensitivity of 75% and 87%, a specificity of 70% and 50% for perinephric involvement, and a sensitivity of 100% and 100%, a specificity of 63% and 54% for renal pelvis involvement. The kappa interobserver agreements for perinephric involvement and renal pelvis involvement were 0.67 and 0.83, respectively. Conclusion: False positive finding of perinephric involvement causes overstaging of Robson stage I disease or in T1-T2 disease of TNM classification. Perinephric stranding may not be reliable or specific findings, and a result of perinephric involvement in CT scan is still limited. MDCT is accurate in the pre-operative evaluation of renal cell carcinoma in Robson stage II-IV disease.

Nasopharyngeal hamartoma: A case report and literature review.

Hamartoma is a non-neoplastic tumoral lesion resulting from a developmental anomaly and is characterized by the existence of cells and mature tissues common to the place of origin. Although hamartoma is common in the lung, kidney, and intestines, it is rare in the nasal cavity, the paranasal sinuses and particularly in the nasopharynx. Within the nasal cavity, the most common site of occurrence is the posterior aspect of the nasal septum. We reported a case of 15-year-old Thai male who presented with chronic rhinitis and left eustachian tube dysfunction for several months. Nasal telescopy revealed one smooth pink mass which originated from the left eustachian tube opening and another mass originated from the roof of the nasopharynx near the posterior part of nasal septum. Tumor removal was performed by endoscopic approach, and left myringotomy and a pressure equalization tube placement was done. No postoperative complications were found. Pathological diagnosis is consistent with hamartoma. After a 3 -month follow-up period, the patient still had a small residual mass in the left eustachian tube without any symptoms. Endoscopic approach enables the satisfactory role in the treatment of this rare condition.

Immunohistochemical study for the diagnosis of Alport's syndrome.

BACKGROUND: Alport's syndrome (AS) is the most common cause of inherited glomerular disease in Thailand. The majority of cases show X-linked inheritance, which is caused by mutations in the gene coding for the alpha5 chain of type IV collagen in the glomerular basement membrane (GBM) and epidermal basement membrane (EBM). Such mutation usually leads to a reduction in protein amount, thus, immunohistochemical studies have been considered in diagnostic evaluation. OBJECTIVE: To study the expression of alpha[IV] collagen chains in the skin as an alternative approach to diagnose AS. MATERIAL AND METHOD: Eleven unrelated probands with proven AS, 7 relatives with abnormal urinalysis, 4 suspected individuals, and 8 normal controls were enrolled. A punch skin biopsy and immunofluorescence staining of the tissue specimens for alpha1, alpha3 and alpha5[IV] collagen chains was performed. RESULTS: The alpha5[IV] chain was absent in the EBM in all male AS patients while a discontinuing pattern was observed in all females except one. The findings are specific for AS with a sensitivity of 91%. Studies in relatives and suspected individuals also confirmed the advantage of this approach as demonstrated by the absence and discontinuation of alpha5[IV] staining in all males and females, respectively. We also analyzed their expressions in the kidney tissue and demonstrated abnormal alpha3 and alpha5[IV] staining in five of six samples. CONCLUSION: Immunohistochemical study of the skin should be used as a screening method in patients suspected of AS, as it is much less invasive. Moreover, it is a useful adjunct to conventional examination of biopsied renal tissue.

The effect of alpha-tocopherol on the oxidative stress and antioxidants in idiopathic IgA nephropathy.

OBJECTIVE: Nearly 25% of IgA nephropathy patients progress to end-stage renal disease over a 20-25 year follow-up period. IgA containing immune complex stimulates oxygen free radical production by mesangial cells in vitro, which may mediate glomerular injury in this disorder. Therefore, we studied whether dietary supplementation with the antioxidant agent, vitamin E, attenuates renal damage in patients with IgA nephropathy. MATERIAL AND METHOD: Twenty-eight patients with idiopathic IgA nephropathy were supplemented with vitamin E 400 mg/day for 6 months. Antioxidant enzymes, glutathione, plasma malondialdehyde (MDA), and renal function were studied after 3 and 6 months therapy. RESULT: The result of the study showed high plasma MDA and significant reduction after therapy (1.15 +/- 0.45 VS 0.86 +/- 0.30 microM, p < 0.0001). The RBC vitamin E was also elevated statistically significantly (5.07 +/- 2.42 VS 15.70 +/- 3.37 microM, p < 0.001). Glutathione peroxidase activities were decreased (38.52 +/- 15.53 VS 23.97 +/- 7.63 U/gHb, p < 0.001). Glutathione was also decreased (44.80 +/- 9.70 VS 32.45 +/- 6.74 mg/dl, p < 0.05) but there were no changes in red cell catalase and superoxide dismutase activities. Creatinine clearance, proteinuria, urine N-acetyl glucosaminidase and beta2-microglobulin also showed no improvement. CONCLUSION: Our data demonstrated the particular group of IgA nephropathy patients with low vitamin E level and high oxidative stress had significant reduction of oxidative stress after vitamin E therapy.

An analysis of 3,555 cases of renal biopsy in Thailand.

BACKGROUND: The knowledge of the epidemiology of biopsied renal diseases provides useful information in clinical practice. There are several epidemiologic population-based studies of biopsy-proven nephropathies with detailed clinicopathologic correlations that could be different according to the country analyzed. OBJECTIVE: To identify the prevalence of primary and secondary glomerular diseases and to study the trend of the pattern changes of the glomerulopathy in Thailand. MATERIAL AND METHOD: A retrospective study of percutaneous renal biopsies during a 23-year period of 1982 to 2005 was performed. A total of 3,555 consecutive native kidney biopsies in adult patients between 12 and 84 years of age were analyzed for the prevalence and changes in the 5-year interval over the two decades. RESULTS: From the clinical trial of 3,275 patients, the ratio between primary and secondary glomerular diseases was 2:1 (2154:1121). The most common primary glomerular disease (2154 patients) were IgM nephropathy (n = 986, 45.8%) followed by IgA nephropathy (n = 386, 17.9%); membranous nephropathy (n = 341, 15.8%); diffuse endocapillary proliferative glomerulonephritis (n = 114, 5.3%) and diffuse crescentic glomerulonephritis (n = 71, 3.3%). Lupus nephritis was the most prevalent cause of secondary glomerulonephritis in the present study (n = 992, 88.5%). Examination of the 5-year interval along the study period revealed a significant increase in the prevalence of IgA nephropathy and diabetic nephropathy. Prevalence of focal and segmental glomerulosclerosis rose by five times over the last two decades in contrast to IgM nephropathy, which prevalence is decreasing. CONCLUSION: There is high prevalence of IgM nephropathy, IgA nephropathy, and lupus nephritis in Thailand which is different from other countries. It could be due to various races and altered environments. The information obtained from these results is an important contribution for the understanding of the prevalence in renal diseases in Thailand. It can be used as the baseline data for making efficient research into the appropriate and beneficial way of management in the future.

A histopathological study of hearts and spleens of hamsters (Mesocricetus auratus) infected with Leptospira interrogans, serovar pyrogenes.

The effects of Leptospira interrogans on the heart and spleen of hamsters were studied histopathologically. Infected hamsters were sacrificed at 1 hour, 6 hours and on days 1, 2, 3, 4, 5 and 6 after inoculation with Leptospira interrogans serovar pyrogenes. The heart and spleen of each of the sacrificed animals were removed and processed for routine conventional light microscopy. Infected hearts showed degenerative change of the cardiac muscle cells composed of cellular swelling, condensation of chromatin granules, pyknotic nuclei and acidophilic cytoplasm. Congestion of the cardiac blood vessels and hemorrhagic areas were found. Necrosis of the cardiac muscle cells was surrounded by numerous inflammatory cells. In the spleen, cellular necrosis was found scattered throughout the splenic cord. The splenic sinusoids were dilated and congested with many hemorrhagic areas. Inflammatory cell infiltration was also noted in the splenic parenchyma and the splenic sinusoids.

Systemic lupus erythematosus in Thai children: clinicopathologic findings and outcome in 82 patients.

OBJECTIVES: To define the patterns of clinicopathologic findings and to identify the risk factors for renal failure and mortality of childhood-onset systemic lupus erythematosus (SLE) in Thailand. MATERIAL AND METHOD: The study is a retrospective analysis of clinical manifestations, laboratory data, and pathologic findings, treatment modalities, and outcome of 82 patients with biopsy-proven lupus nephritis (LN) with disease onset between I January 1987 and 31 December 1997. All children developed these first manifestations at the age 13 years or under RESULTS: Sixty-four (789%) patients were females and eighteen (22%) were males (ratio female/male = 3.5:1). The patients were followed for a mean period of 53.6 months (range 1 -141). The mean age at disease onset was 9.2 years (range 2-12.6). Class-IV LN, observed in 40 (48.8%) patients, was the most frequent histopathology on initial renal biopsy. Less frequent findings were class-II (30.5%), V (14.6%), I (3.7%) and III (2.4%) LN. Based on the renal histopathology and clinical presentations, patients were treated with corticosteroids alone or in combination with azathioprine or with intravenous cyclophosphamide (CYC). Methylprednisolone pulses were given in patients with clinically more severe disease. Follow-up biopsies, performed in 12 patients, showed no change in 4 patients, and were progressive in 8 patients. On final clinical evaluation, 20 patients died, 65% died from serious infections, 15% from cardiopulmonary complications, and 10% from end stage renal disease. As the whole group, survival rates were 89% and 74% at 12 and 60 months, respectively. The 5-year patient survival in class-II, class-IV and class- VLN patients were 83%, 67% and 64%, respectively. Within the group of class-IV LN, the 5-year survival in the patients treated with intravenous CYC was significantly better than those receiving prednisolone with or without azathioprine. Five-year kidney survival rates from the time of diagnosis to the endpoints of terminal renal failure were 94% for the whole group, and 100%, 96%, 91% in the class- V, class-II, and class-IV group, respectively. Initial presence of hypertension, hematuria, renal insufficiency were independent factors significantly associated with lower patient survival probabilities. There was no association of either patient and kidney survival with gender, age, cytopenia, and autoantibody level. CONCLUSIONS: Infectious complications were the most common cause of morbidity and mortality in our pediatric patients with SLE. The immunosuppressive agents used to treat SLE seemed to be a major contribution to the patient survival. With judicious use of corticosteroid, intravenous CYC in severe SLE showed superior efficacy over oral prednisolone with or without azathioprine.

Effect of fish oil on oxidative stress, lipid profile and renal function in IgA nephropathy.

The omega-3 polyunsaturated fatty acids in fish oil have been shown to produce beneficial effects, such as a reduction in blood pressure, proteinuria, lipid levels and inflammation. Aggregated immunoglobulin A obtained from IgA nephropathy patients induced greater oxygen free radicals in polymorphonuclear leukocytes than other glomerulopathy. All of which may affect the course of IgA nephropathy. Twenty-three adult patients with biopsy proven IgA nephropathy, with proteinuria more than 1 g/day, serum creatinine less than 3 mg/dl and blood pressure control less than 130/80 mmHg were given omega-3 polyunsaturated fatty acids (PUFA) in the form of an Omacor capsule 4 g/day equivalent to eicosapentaenoic acid (EPA) 1.88 g and docosahexaenoic acid (DHA) 1.48 g for 6 months. A 3 to 6 month follow-up was planned, with monthly evaluations of the patients. By six months, the serum triglyceride was significantly reduced (143.45 +/- 62.65 vs 91 +/- 42.89 mg/dl, p = 0.002), serum cholesterol was also reduced but not statistically significant (234.16 +/- 56.29 vs 219.76 +/- 51.25 mg/dl, p = 0.07). There was a trend of increased serum high density lipoprotein (HDL)-cholesterol (39.26 +/- 10.56 vs 42.72 +/- 8.37 mg/dl, p = 0.056). Urine beta-2-microglobulin was elevated in IgA patients and decreased statistically significant after 3 months (453 +/- 580 vs 308 +/- 274 microg/24 h, p < 0.001) and 6 months of fish oil therapy (453 +/- 580 vs 142 +/- 182, p < 0.03) while urine N-acetyl-glucosaminidase (NAG) was of no significant difference both before and after fish oil administration (21 +/- 10 vs 22 +/- 10 and 21 +/- 9 U/24 h, p = 0.08). Plasma malondialdehyde (MDA), the end product of oxidative stress was statistically, significantly decreased (1.09 +/- 0.51 vs 0.89 +/- 0.49 nmol/L, p = 0.003). The study did not show any change in blood pressure, proteinuria, or serum creatinine. The authors conclude from the results of this study that patients with idiopathic IgA nephropathy with proteinuria and mildly reduced GFR did not benefit from short-term treatment with 4 g per day of omega-3 PUFA regarding the total protein excretion and glomerular filtration rate (GFR), but the advantage was the improvement in tubular dysfunction, lipid profiles, and oxidative stress.

Percutaneous renal biopsy in children.

The authors studied the percutaneous renal biopsies performed in the Department of Pediatrics, Siriraj Hospital from January 2000 to March 2001 in order to evaluate the safety and benefit of the procedure. Eighty-five patients (90 episodes) were included in the study, aged 7.8+/-3.7 year (range 16 months to 16 years), with a male to female ratio of 1.2:1. Nephrotic syndrome (42.3%) and systemic lupus erythematosus (23.5%) were the two most common indications for biopsy. The kidney was localized by ultrasound prior to the procedure in nearly all cases (97.7%). Premedication with Ketamine was adequate in most patients (91.1%). A modified 13 G Vim-Silverman needle was used to obtain 1-4 biopsy cores. The mean number of glomeruli obtained was 44.0+/-29.9, with failure to obtain renal tissue in 6 episodes (6.6%). Percutaneous biopsy was performed twice in one patient without success and the patient eventually underwent an open biopsy. The most common complication was hematuria (74.4%), of these, gross hematuria was found in 23.3 per cent. Blood transfusion was needed in 2 patients, one of them also needed embolization to control bleeding. Transient hypotension occurred in 1 patient. Transient hypertension occurred in 6 episodes (6.6%). Muscle twitching occurred in 2 episodes and was treated with diazepam intravenously. Hypertension and muscle twitching only occurred in those who received ketamine. The Clinical Benefit Score was 2 (information yielding a definite diagnosis and/or prognosis, alternatively allowing a change in, or support of, therapy) in 89.4 per cent. It was concluded that the present practice of renal biopsy is safe, with high clinical benefit score. It remains to be studied whether an ultrasound guidance biopsy with a newer biopsy device will lower the incidence of complications even further.

Chronic granulomatous disease with disseminated trichosporonosis: A case report.

A case of a two year and three month old Thai boy with a history of recurrent bacterial infections since aged 2 months. A definite absence of superoxide activity in the patient' s granulocytes detected by nitroblue tetrazolium test indicated the diagnosis of chronic granulomatous disease. He suffered from septicemia and systemic fungal infection, resulting in death despite rigorous medical care. The postmortem findings showed extensive granulomatous inflammation in several internal organs. Tissue culture led to diagnosis of disseminated Trichosporonosis, an uncommon infection in immunocompromised patients. This is the first case report of disseminated trichosporonosis in a chronic granulomatous disease patient.

Significance of thyroglobulin in thyroid diseases detected by the immunoperoxidase method.

Thyroglobulin (TG) is a protein that synthesized from the thyroid follicular epithelium and can reflect the thyroid gland in origin together with the cellular activity. The aim of this study is to detect TG qualitatively and semiquantitatively by immunoperoxidase method in various thyroid lesions. The result shows that all of the nodular goitre (43 cases), primary diffuse hyperplasia (18 cases), adenoma 60 cases, papillary carcinoma (43 cases) and follicular carcinoma (22 cases) show cytoplasmic staining of TG in varying pattern and intensity, while only 3 out of the 7 anaplastic carcinoma show irregular cytoplasmic staining. These findings can be used in identifying the thyroid gland in origin in the metastatic lesion and the functional status of the lesion.

IgA nephropathy in Thai children.

We retrospectively studied 11 patients with IgA nephropathy admitted into the Department of Pediatrics, Siriraj Hospital from 1983 to 1993. These patients represented 2 percent of 552 patients with glomerular disease admitted at the same duration. Female to male ratio was 1.75 : 1. Average age of onset was 98.5 months (range 46-144 months). Common manifestations included macroscopic hematuria (72.7 percent), microscopic hematuria 1 patient (9.1 percent), edema (27.3 percent) and nephritic syndrome (18.2 percent). Proteinuria was found in 4 patients (36.2 percent) and 3 patients (27.2 percent) had increased serum creatinine concentration at the time of diagnosis. Serum immunoglobulin A was increased in 1 of 5 patients studied (20 percent). Percutaneous renal biopsy was performed in all cases. Nine patients had diffuse proliferative glomerulonephritis, the rest had focal segmental glomerulonephritis. Both patients with nephritic syndrome were given oral prednisolone and 1 patient with proteinuria and severe renal pathology was given the combination of prednisolone and cyclophosphamide, all responded well. Seven patients had been followed up for 1 to 9 years. Three patients (42.8 percent) had increased serum creatinine. We suggest that urine protein and renal function should be measured in all patients with IgA nephropathy at diagnosis and followed up periodically. We also recommend the use of prednisolone in patients with IgA nephropathy who presented with nephritic syndrome.

Pregnancy complicated with SLE and RPGN : A case report.

Pregnancy complicated with systemic lupus erythematosus (SLE) is notoriously variable in its presentation, course, and outcome. Renal involvement is demonstrated in half of patients. Exaggerated by pregnancy on renal function is not concluded. But renal failure is one of the leading causes of death. We report a case of lupus complicating pregnancy that no prepregnancy remission. She developed clinically pre-eclampsia and lupus nephritis in 17 weeks gestation. Flares of disease with deterioration of renal function despite corticosteroid therapy lead to stop pregnancy. Although pregnancy has been terminated, she became worse and died before starting hemodialysis. Histologic study from renal necropsy and clinical manifestation consistented with rapidly progressive glomerulonephritis (RPGN).

End-stage renal failure in children with autosomal dominant polycystic kidney disease.

Clinical presentaiton of autosomal dominant polycystic kidney disease in childhood is uncommon. When present, it is most commonly abdominal mass. Some children may present with hypertension, hematuria, or abdominal pain without enlargement kidneys but renal failure is rare and has never been reported in Thailand. We report a 10-tear-old Thai boy with end-stage renal failure due to Autosomal dominant polycystic kidney disease diagnosed by renal autopsy.

Nephropathy associated with wilms’ tumor (drash syndrome).

Nephropathy associated with Wilms’ tumor (Drash syndrome) is an uncommon disease with well-documented clinical course and prognosis regarding kidney function. We report a girl with Drash syndrome who presented with Wilms’ tumor and aniridia at the age of one year. Left nephrectomy with chemotherapy and radiotherapy were given. She remained in good health with normal renal function during the 7 years period of follow up. At the age of 9 years, she developed acute nephrotic syndrome, hypertension, and renal failure (GFR 15ml./min/1.73 square meter). Abdominal ultrasound revealed no evidence of Wilms’ tumor recurrence. Prednisolone, cyclophosphamide, and antihypertensive drugs were given. Renal function returned to normal (GFR 80/ml/min/1.73 square meter) at one month and serum albumin at 3 months after treatment. The case of nephropathy associated with Wilms’ tumor presented here has an atypical clinical manifestation as compared with the literature concerning it may throw some light on the pathogenesis of glomerulopathy in Drash syndrome.

“Epithelioid hemangioendothelimoma” an unusual lung tumor: A case report.

A 18-year-old Thai woman with preceding asymptomatic skin nodules for 4 years was admitted for the evaluation of progressive dyspnea during the past 4 months. The findings of iron deficiency anemia with diffuse nodular pulmonary infiltrates led to the open lung biopsy with simultaneous skin biopsy. The final pathological diagnosis was epithelioid hemangioendothelioma. Possible primary soft tissue tumor with lung and liver metastasis was postulated from the clinical findings ad investigative results.

Systemic fungal infection: A study of 138 autopsies.

A study of 138 autopsy cases with deep fungal infections out of a total of 3328 autopsy cases during the period 1980 to 1985 was carried out when the causal organisms were determined, 160 infections were found: 10 were caused by pathogenic fungi (Crytococcus neoformans) and the other 10 were caused by opportunistic fungi including aspergillus, candida, mucor and penicillium. A combination of more than one fungus was noted in 21 cases. The central nervous system was most likely to be affected by crytococcus, whereas the respiratory and alimentary systems were infected by aspergillus and candida, respectively. In this study, males were somewhat more commonly affected than females. Fungal infections were common in those who had underlying diseases, internal malignancies, diabetes mellitus as well as in patients with a history of prolonged use of antibiotics and corticosteroids. Compared with a previous study in the same hospital, the incidence definitely increased, although the other patterns of the systemic fungal infections showed no significant change.

Paratesticular rhabdomyosarcoma : Report of a case.

Rhabdomyosarcoma is one of the most common soft tissue sarcomas in childhood and adolescent. It usually involves the orbital and pelvic portions of the genitourinary tract and less commonly, the paratesticular tissue. Our report here is of a Thai male who complained of a painless slow growing mass in the left testicular region for 2 years. This mass was noted to have rapidly increased in size within 2 months prior to admission. Only left orchidectomy was performed and the pathological diagnosis was paratesticular embryonal rhabdyosarcoma.