Long-Term Persistence of Chikungunya Virus-Associated Manifestations and Anti-Chikungunya Virus Antibody in Southern Thailand: 5 Years After an Outbreak in 2008-2009.

Chikungunya fever, a disease caused by chikungunya virus (CHIKV), reemerged and affected over 52,000 people in southern Thailand in 2008 and 2009. The CHIKV strain involved in this outbreak was the East Central South African (ECSA) strain with the E1-A226V mutation. The prevalence of CHIKV-associated chronic discomfort varied by virus lineage. This retrospective cohort study aims to describe the CHIKV-related symptoms persisting in CHIKV-affected patients, related factors, and the presence of anti-CHIKV immunoglobulin G (IgG) antibodies 5 years after the onset of disease. From 5,344 of the study population screened, a total of 89 affected patients reported persistent arthralgia 5 years after the disease onset (nonrecovery rate = 1.7%). Of the 141 affected patients enrolled, 122 cases (86.5%; 77 cases with persistent arthralgia and 45 cases of fully recovered) still had detectable levels of anti-CHIKV IgG antibodies. Long-term persistence of chronic joint symptoms is associated with the severity of the disease during the initial phase of the infection, but not gender, age, or comorbidities. The common manifestations were arthralgia (75.3%), morning joint stiffness (39.0%), muscle pain (19.5%), and occasional joint swelling (16.9%). Chronic joint symptoms could occur in either a fluctuating or a persistent manner and usually caused moderate pain. The joints affected were mainly fingers (71.4%), wrists (51.9%), and knees (50.6%). Most patients had polyarthralgia with symmetrical joint involvement. In some cases with persistent arthralgia, atypical manifestations, including severe depression with suicide attempts, severe weight loss, and severe hair loss, were found, and some patients still experienced severe joint pain.

Proinflammatory Cytokines and Chemokines as Biomarkers of Persistent Arthralgia and Severe Disease After Chikungunya Virus Infection: A 5-Year Follow-Up Study in Southern Thailand.

Chikungunya fever is a re-emerging viral disease caused by chikungunya virus (CHIKV). The disease is generally self-limiting, but chronic arthralgia/arthritis may persist for months or years. We evaluated the expression of 12 cytokines/chemokines and matrix metalloproteinases (MMP)-1 and MMP-3 using enzyme-linked immunosorbent assays (ELISAs) and compared among patients who still had arthralgia (persistent arthralgia), patients who had fully recovered, and healthy controls. There was a significant increase in interleukin (IL)-1ß, IL-6, IL-8, monocyte chemotactic protein-1 (MCP-1), MMP-1, and MMP-3 levels in patients with persistent arthralgia in comparison to healthy controls (p < 0.05) and a significant increase in tumor necrosis factor-alpha (TNF-α), MMP-1, and MMP-3 levels in patients with persistent arthralgia in comparison to patients who had fully recovered (p < 0.05). Interferon (IFN)-γ, IL-6, and transforming growth factor beta (TGF-ß) levels tended to be increased in patients with chronic CHIKV-induced arthritis compared with fully recovered. TNF-α, IL-12, and MCP-1 levels were elevated (p < 0.05), whereas regulated on activation, normal T cell expressed and secreted (RANTES) levels were decreased in patients with severe pain compared with patients with nonsevere pain (p < 0.05). IFN-γ, IL-1ß, IL-6, and IL-8 levels tended to be elevated in patients with severe pain compared with patients with nonsevere pain. We proposed a role played by TNF-α, IL-6, IL-8, and MCP-1 in persistent arthralgia or chronic disease through the activation of MMP-1 and MMP-3. The increase in TNF-α, IL-12, and MCP-1 levels (and the tendency toward an increase in IFN-γ, IL-1ß, IL-6, and IL-8 levels) in patients with severe pain compared with patients with nonsevere pain suggests the role of these inflammatory markers in chronic disease and severity of the disease.

Primary synovial sarcoma of the abdominal wall: a case report and literature review.

Synovial sarcoma (SS) is the fourth most common type of soft tissue sarcoma, following malignant fibrous histiocytoma, liposarcoma, and rhabdomyosarcoma. It usually occurs in the extremities near the large joints of middle-aged patients. We describe a case of synovial sarcoma of the anterior abdominal wall (SSAW) in an adolescent girl and undertake a review of the literature.

Renal pelvic villous adenoma presented with mucusuria: report of a case and literature review.

Villous adenomas of the urinary tract are an uncommon condition, and appear mostly in patients where the disease occurred in the lower urinary tract. In contrast, upper urinary tract villous adenomas are a rare condition. Currently, just three cases of villous adenoma in the renal pelvis have been published. Herein, we present the fourth case of a renal pelvic villous adenoma, along with muconephrosis and mucusuria. A 73-year-old man presented with abdominal discomfort and a palpable abdominal mass. He had a history of bilateral anatrophic nephrolithotomy, 8 years and 6 years earlier. The preoperative radiographic investigation showed severe right hydronephrosis. A right nephrectomy was carried out and the intraoperative finding showed severe perinephric adhesion and a great deal of mucus in the renal pelvis. The pathological examination showed a villous adenoma and urothelial metaplasia in the kidney.

Extranodal NK/T-cell lymphoma, nasal type, includes cases of natural killer cell and αß, γδ, and αß/γδ T-cell origin: a comprehensive clinicopathologic and phenotypic study.

Extranodal NK/T-cell lymphoma (ENKTL), nasal type, may be of NK or T-cell origin; however, the proportion of T-ENKTLs and whether they are of αß or γδ type remains uncertain. To elucidate the cell of origin and detailed phenotype of ENKTL and assess any clinicopathologic associations, 67 cases of ENKTL from Thailand were investigated, together with 5 γδ enteropathy-associated T-cell lymphomas (EATLs) for comparison. In all, 70% of the ENKTL were T-cell receptor (TCR) ß,γ and, in cases tested, δ negative (presumptive NK origin); 5% were TCR γδ, 3% were TCR αß, 1% were TCR αß/γδ, and 21% were indeterminate. Out of 17 presumptive NK-ENKTLs tested, 3 had clonal TCR rearrangements. All cases were EBV and TIA-1; >85% were positive for CD3, CD2, granzyme B, pSTAT3, and Lsk/MATK; and all were CD16. Presumptive NK-ENKTLs had significantly more frequent CD56 (83% vs. 33%) and CXCL13 (59% vs. 0%) but less frequent PD-1 (0% vs. 40%) compared with T-ENKTLs. Of the NK-ENKTLs, 38% were Oct-2 compared with 0% of T-ENKTLs, and 54% were IRF4/MUM1 compared with 20% of T-ENKTLs. Only αß T-ENKTLs were CD5. Intestinal ENKTLs were EBV and had significantly more frequent CD30, pSTAT3, and IRF4/MUM1 expression but less frequent CD16 compared with γδ EATL. Significant adverse prognostic indicators included a primary non-upper aerodigestive tract site, high stage, bone marrow involvement, International Prognostic Index ≥2, lack of radiotherapy, Ki67 >40%, and CD25 expression. The upper aerodigestive tract ENKTLs of T-cell origin compared with those of presumptive NK origin showed a trend for better survival. Thus, at least 11% of evaluable ENKTLs are of T-cell origin. Although T-ENKTLs have phenotypic and some possible clinical differences, they share many similarities with ENKTLs that lack TCR expression and are distinct from intestinal γδ EATL.

Effects of autogenous growth factors on heterotopic bone formation of osteogenic cells in small animal model.

AIMS: This study used a new approach to investigate the effective concentrations of growth factors released from platelet concentrate (PC) on the bone formation capacity of osteogenically differentiated rat bone marrow stromal cells (rBMSCs). MATERIALS AND METHODS: Rat BMSCs and whole blood were harvested from 40 adult male Spraque-Dawly rats. Rat BMSCs were expanded in an osteogenic medium and seeded on inert collagenous bovine bone matrix (ICBM). Growth factors released from degranulated PC (GFs) containing TGF-ß1 1 (25ng/ml)-10ng (250ng/ml) and rhBMP-2 400ng (10µg/ml) were suspended in 40µl platelet poor plasma (PPP) and applied on the ICBM-rBMSC constructs or ICBM only, respectively. The constructs were then transplanted in autologous hosts for 4 weeks. Concurrently, osteoblastic differentiation of rBMSCs on ICBM-rBMSC-PPP constructs was characterized in vitro. RESULTS: Rat BMSCs in osteogenic medium exhibited phenotypes of mature osteoblasts. The amount of newly formed bone among groups of ICBM-rBMSC-PPP with and without GFs was not significantly different (p>0.05) and was significantly lower than a group of ICBM-PPP-BMP-2 (p<0.05). CONCLUSIONS: Autogenous GFs had no effect on the capacity of rBMSCs to form new bone. The ability to measure the bone formation capacity of transplanted autologous cells and growth factors in a small animal model was demonstrated.

Effects of long-term use of antiretroviral therapy on the prevalence of oral Epstein-Barr virus.

BACKGROUND: The objectives of this study were to determine (i) the prevalence of oral Epstein-Barr virus (EBV) in HIV-infected subjects compared to non-HIV controls and (ii) the effects of long-term use of antiretroviral therapy (ART) on the prevalence of oral EBV. METHODS: A cross-sectional study was performed in HIV-infected subjects with and without ART, and non-HIV individuals. DNA in saliva samples was extracted and used as a template to detect EBV BamH1W and EBNA1 by quantitative polymerase chain reaction. Student t-test and ANOVA test were performed to determine the prevalence rates among groups. RESULTS: Forty-nine HIV-infected subjects: 37 on ART (age range 23-54 year, mean 37 year), 12 not on ART (age range 20-40 year, mean 31 year), and 20 non-HIV controls (age range 19-53 year, mean 31 year) were enrolled. The numbers of EBV BamH1W in saliva were found to be significantly higher in HIV-infected subjects than non-HIV controls (80% vs. 20%, mean = 12118 vs. 134 copies/10(5) cells, P < 0.001). HIV-infected subjects who were on ART had significantly lower numbers of EBV BamH1W than those who were not (mean = 4102 vs. 138613 copies/10(5) cells, P = 0.011). The numbers were significantly lower in those who received long-term ART compared with short-term (mean = 1401 vs. 11124 copies/10(5) cells, P = 0.034). No significant difference was observed between the groups when using EBNA1 primers. CONCLUSIONS: Prevalence of oral EBV was significantly higher in HIV-infected subjects than non-HIV-controls. The numbers of the virus were significantly decreased by ART. Long-term use of ART did not increase oral EBV.

Impacts of HIV infection and long-term use of antiretroviral therapy on the prevalence of oral human papilloma virus type 16.

BACKGROUND: The objectives of this study were to determine (i) the prevalence and the copy numbers of oral human papilloma virus type 16 (HPV-16) in HIV-infected patients compared with non-HIV controls, and (ii) the effects of antiretroviral therapy (ART) and its duration on the virus. METHODS: A cross-sectional study was carried out in HIV-infected patients with and without ART and in non-HIV controls. Saliva samples were collected, and the DNA extracted from those samples was used as a template to detect HPV-16 E6 and E7 by quantitative polymerase chain reaction. Student's t-test and ANOVA test were performed to determine the prevalence rates among groups. RESULTS: Forty-nine HIV-infected patients: 37 on ART (age range, 23-54 years; mean, 37 years), 12 not on ART (age range, 20-40 years; mean, 31 years), and 20 non-HIV controls (age range, 19-53 years; mean, 31 years) were enrolled. The prevalence of oral HPV-16 infection and the copy numbers of the virus were significantly higher in HIV-infected patients than in non-HIV controls when using E6 assay (geometric mean = 10696 vs. 563 copies/10(5) cells, P < 0.001), but not E7 assay. No significant difference was observed between those who were and were not on ART. Long-term use of ART did not significantly change the prevalence of oral HPV-16 infection and the copy numbers of the virus (P = 0.567). CONCLUSION: We conclude that the prevalence of oral HPV-16 infection and the copy numbers of the virus are increased by HIV infection. Neither the use of ART nor its duration significantly affected the virus.

Epstein-Barr virus strains defined by the latent membrane protein 1 sequence characterize Thai ethnic groups.

Epstein-Barr virus (EBV) is ubiquitous in the human population and seroepidemiological studies have revealed that more than 90% of adults are infected with the virus in Thailand. It has been suggested that latent membrane protein 1 (LMP1) variants may differ in their tumorigenicity and geographical localization. The distribution of LMP1 variants of EBV in the Thai population was studied. A total of 259 LMP1 sequences from ten Thai ethnic groups (Lahu, Lisu, Shan, Red Karen, White Karen, Hmong, Akha, Mlabri, Moken and Urak Lawoi) were studied using direct PCR sequencing. Nucleotide sequences corresponding to the C terminus of the LMP1, including previously published sequences from central and southern Thais, were used in the phylogenetic analysis. Five strains--the B95-8 prototype, China 1, China 2, Mediterranean (Med) and SEA 2--were identified in ethnic groups in Thailand. The major strain and the distribution pattern differed by group and location. When the ethnic groups were classified by linguistic group, the prevalence of the SEA 2 strain was significantly different between Austro-Thais and other linguistic groups (P=0.0001), whereas, among Tibeto-Burman linguistic groups, the prevalence of the Med strain was different between matrilocal and patrilocal groups (P=0.0245). The distribution of LMP1 strains in ethnic minorities in Thailand is associated with ethnogeographical factors and the social/marriage system. This study thus provides evidence for the importance of interactions between populations in virus diversity.

Correlation of epidermal growth factor receptor mutation, immunohistochemistry, and fluorescence in situ hybridization in esophageal squamous cell carcinoma.

BACKGROUND: The epidermal growth factor receptor (EGFR) has become a promising target for novel anticancer therapy Evaluation of its biological profiles including gene mutation, amplification, and protein expression in esophageal squamous cell carcinoma (ESCC) is essential to establish the EGFR molecular feature(s) suitable to select patients in anti-EGFR therapy. MATERIAL AND METHOD: The subjects' specimens of ESCC at Songklanagarind Hospital were obtained and investigated for EGFR protein expression and gene amplification. Polymerase chain reaction (PCR) was performed to amplify the EGFR DNA product. The mutational status of EGFR exons 19 and 21 was analyzed using direct sequencing. The entire biological profiles of the EGFR were then correlated. RESULTS: There were 48 eligible ESCC specimens. No somatic mutation in the tyrosine kinase domain of EGFR was detected A high level of EGFR protein was exhibited in 22 patients (46%). Twenty-three patients (48%) had shown a high gene copy numbers. However, no direct correlation between EGFR protein and gene status was observed. CONCLUSION: EGFR mutations in the tyrosine kinase domain of exons 19 and 21 were absent in ESCC, whereas, protein overexpression and gene amplification was prevalent. Therefore, selection of ESCC patients for studies with anti-EGFR agents based on protein expression or gene copy number, not gene mutation, is rational.

Quantitative analysis of cell-free Epstein-Barr virus DNA in the plasma of patients with peripheral T-cell and NK-cell lymphomas and peripheral T-cell proliferative diseases.

BACKGROUND: The level of circulating EBV DNA is a prognostic marker in patients with some EBV-associated malignant diseases. OBJECTIVES: To investigate the presence and nature of Epstein-Barr virus (EBV) DNA in the plasma and to evaluate the correlation of plasma concentrations of EBV DNA with the EBV genomic status in peripheral blood T-cells and neoplastic cells and with the clinical outcome of patients with peripheral T-cell and NK-cell lymphomas (PTCL) and peripheral T-cell proliferative diseases (PTPD). STUDY DESIGN: EBV DNA in the plasma of 45 patients and 45 controls was measured using real-time PCR. The presence of the EBV genome in the isolated peripheral blood lymphocytes (CD3+ and CD3- cells) was analysed by PCR. Detection of EBV-encoded early RNA (EBER) in corresponding tumor tissues was carried out using in situ hybridization. DNase I digestion was applied to plasma samples to detect naked EBV DNA. RESULTS: Cell-free EBV DNA was detected in 32/38 (84%) of PTCL patients and 5/7 (71%) of PTPD patients, but not in the controls. Patients with EBV genome in peripheral blood CD3+ cells and EBV genome (EBER) in the tumor cells, compared to those without these findings, had significantly higher plasma EBV DNA levels. The majority of circulating EBV DNA molecules was naked form. The plasma EBV DNA levels were not related to survival. CONCLUSIONS: The concentration of EBV DNA in the plasma was not a prognostic marker in PTCL and PTPD patients.

Primary pigmented nodular adrenocortical disease with synaptophysin immunoreactivity in two thai children.

This paper reports the cases of two Thai children diagnosed with primary pigmented nodular adrenocortical disease (PPNAD). The first was a thirteen and a half year old male who presented with Cushing syndrome for three years and severe osteoporosis. He had hypercortisolemia, a non-suppressible dexamethasone suppression test, and low serum ACTH. A CT scan showed slight enlargement of both adrenal glands. A bilateral adrenalectomy was performed. The second case was a thirteen-year old female who presented with mild Cushing syndrome for one year with paradoxical response to high-dose dexamethasone suppression test. An MRI revealed suspected microadenoma of the left adrenal gland. Blood sampling showed a higher cortisol level from the left adrenal vein than from the right. A left adrenalectomy was performed, followed by a right adrenalectomy four months later. The pathologies were compatible with PPNAD. Immunostaining for synaptophysin was done in both patients. The cells in the adrenocortical micronodules of both cases were stained intensely with antiserum for synaptophysin, whereas the surrounding adrenal cortex did not.

Effect of thread pitch on pull-out strength of laparoscopic myoma screws.

AIM: The purpose of this study was to evaluate the effect of thread-pitch on pull-out strength and bending strength of buttress-thread screws designed for laparoscopic myoma extraction. METHODS: The ultimate failure load of four 5-mm diameter buttress-thread screws with 3-, 4-, 5-, and 6-mm thread pitch, 40 mm in thread-length were examined on fresh myoma specimens. The myoma tissue at each traction site was evaluated histologically to determine its density. The critical minimal pull-out strength based on moderate-density myoma group was estimated. The bending strength was also determined for each screw. RESULTS: A wide range of ultimate failure loads with a mean +/- SE of 129.3 +/- 5.5 N (range, 30.4-255.7 N) for all screws and tissue densities was recorded. In moderate-density myomas, the mean ultimate failure loads decreased linearly with increasing thread-pitch from 3 mm (148.0 +/- 9.5 N) to 6 mm (119.8 +/- 9.4 N) (test for trend: P < 0.05). Based on the criterion of a minimum pull-out strength of at least 50 N in not less than 95% of tractions in medium-density myomas, the 3-mm and 5-mm pitch screws were found to have acceptable properties. The 5-mm pitch screw had less thread-turn than the 3-mm pitch for the same thread-length and would need less application time. The bending strength also decreased with increasing thread pitch from 3 to 5 mm, then became stable at around 15 N. CONCLUSIONS: The pull-out strength of soft tissue buttress-thread screws decreased linearly with increasing thread-pitch. Thread-pitch should be considered when designing laparoscopic myoma-screws.

Clinical and epidemiological analyses of human pythiosis in Thailand.

BACKGROUND: Pythiosis is an emerging and life-threatening infectious disease in humans and animals that is caused by the pathogenic oomycete Pythium insidiosum. Human pythiosis is found mostly in Thailand, although disease in animals has been increasingly reported worldwide. Clinical information on human pythiosis is limited, and health care professionals are unfamiliar with the disease, leading to underdiagnosis, delayed treatment, and poor prognosis. METHODS: To retrospectively study the clinical and epidemiological features of human pythiosis, we analyzed clinical data from patients with pythiosis diagnosed during the period of January 1985 through June 2003 at 9 tertiary care hospitals throughout Thailand. RESULTS: A total of 102 cases of human pythiosis were documented nationwide. A substantial proportion (40%) of cases occurred in the last 4 years of the 18-year study interval. Clinical presentations fell into 4 groups: cutaneous/subcutaneous cases (5% of cases), vascular cases (59%), ocular cases (33%), and disseminated cases (3%). Almost all patients with cutaneous/subcutaneous, vascular, and disseminated pythiosis (85%) had underlying thalassemia-hemoglobinopathy syndrome. Most ocular cases (84%) were associated with no underlying disease. A majority of the patients were male (71%), were aged 20-60 years (86%), and reported an agricultural occupation (75%). Regarding treatment outcomes, all patients with disseminated infection died; 78% of patients with vascular disease required limb amputation, and 40% of these patients died; and 79% of patients with ocular pythiosis required enucleation/evisceration. CONCLUSIONS: Here, we report, to our knowledge, the largest case study of human pythiosis. The disease has high rates of morbidity and mortality. Early diagnosis and effective treatment are urgently needed to improve clinical outcomes. Because P. insidiosum is distributed worldwide and can infect healthy individuals, an awareness of human pythiosis should be promoted in Thailand and in other countries.

Analysis of LMP1 variants of EBV in Southern Thailand: evidence for strain-associated T-cell tropism and pathogenicity.

BACKGROUND: The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) has sequence heterogeneity. Some of the variants are associated with altered tumorigenic activity and show geographically specific localization. In Thailand, the EBV genome is frequently detected in circulating T cells of T-cell diseases. OBJECTIVE: To determine the role of EBV LMP1 variation in the genesis of T-cell diseases, we focused on virus factors and analyzed EBV strains in Thailand. STUDY DESIGN: EBV DNA was extracted from 18 healthy individuals and 45 patients with T-cell diseases in Southern Thailand and 30 healthy individuals in Central Thailand. By using PCR-direct sequencing method, nucleotide sequences corresponding to the carboxyl terminus of the LMP1 were determined. RESULTS: Four known strains, B95-8 prototype, China 1, China 2 and Mediterranean (Med) and two novel strains, Southeast Asia 1 (SEA 1) and Southeast Asia 2 (SEA 2) were identified. The prevalence of China 2 strain was significantly different (p=0.006) between Central and Southern Thailand. Higher prevalence (p=0.026) of 30-bp deletion type in the Southern Thais was observed. The LMP1 Med strain was associated with the worse prognosis (p=0.029). Among T-cell diseases patients, CD3(+)-cell oriented infection was recognized in SEA1 strain (p=0.025). CONCLUSION: The distribution of EBV strains may be associated with geographic/ethnic and clinical background in the Thai population. Certain EBV strains defined by their LMP1 sequence may influence cell tropism, disease association, or disease severity.

Epstein-Barr virus-associated extranodal non-Hodgkin's lymphoma of the sinonasal tract and nasopharynx in Thailand.

Epstein-Barr virus (EBV) infection is highly associated with specific subtypes of malignant lymphoma. In our previous report on nodal malignant lymphoma in Thailand, we found that 64% of classical Hodgkin's lymphoma (cHL), 51% of non-Hodgkin's lymphoma, T-cell (NHL-T), and 13% of non-Hodgkin's lymphoma, B-cell (NHL-B) were EBV-related. In the present research, we conducted a retrospective study of primary extranodal non-Hodgkin's lymphoma of the sinonasal tract (e-NHL-ST) and primary extranodal non-Hodgkin's lymphoma of the nasopharynx (e-NHL-NP) in Southern Thailand, between 1997 and 2004. EBV-encoded RNA (EBER) expression by in situ hybridization was performed in all cases and a T-cell receptor (TCR)-g gene rearrangement study was performed in NHL-T cases. There were 18 cases of e-NHL-ST and 42 cases of e-NHL-NP detected by histologic and immunohistochemistry examinations. The percentages of e-NHL-ST and e-NHL-NP as compared to nodal malignant lymphoma were 3.7% and 6.8%, respectively. Sixteen cases (88.9%) of e-NHL-ST and 7 cases (16.7%) of e-NHL-NP were NHL-T, and the remainder were NHL-B. All of the NHL-T cases in both sites were EBER-positive. Two (5.4%) of the NHL-B cases in the nasopharynx showed EBER positive. Monoclonal bands of the TCR-gamma gene were detected in 71.4% of the extranodal NK/T-cell lymphomas, nasal type, patients; 50.0% of peripheral T-cell lymphoma, unspecified, patients; and one case of angioimmunoblastic T-cell lymphoma. This study indicates a very strong association of NHL-T in the sinonasal tract or nasopharynx with EBV infection, the link apparently being weaker in NHL-B patients. The study also indicates that most cases of extranodal NK/T-cell lymphoma, nasal type, are not the germline configuration of the TCR genes.

Congenital and infantile nephrotic syndrome in Thai infants.

Congenital and infantile nephrotic syndrome reported from the Eastern world is rare and might be a different entity from that in the West. In a retrospective review of 10 nephrotic syndrome in Thai infants (5 girls and 5 boys), 7 were diagnosed with congenital nephrotic syndrome and 3 with infantile nephrotic syndrome. Two had congenital nephrotic syndrome secondary to congenital syphilis. All had edema, ascites, and failure to thrive. Of the 3 patients tested for thyroid function, all showed hypothyroidism. Two patients developed renal failure. Renal tissue was examined from 4 patients from 3 biopsies and 2 autopsies; only 1 patient showed tubular microcysts. Symptomatic therapy was performed concurrently with penicillin therapy in 2 patients having congenital syphilis. Prednisolone, cyclophosphamide, captopril, and enalapril were tried in some patients, with little effect. Five patients died from respiratory failure complicated by later infection, 1 patient died from renal failure, and 4 patients were lost to follow-up. Nephrotic syndrome in the first year of life in the Eastern world is rare. Prognosis of nephrotic syndrome in Thai infants at this time is still poor.

Epidermal growth factor receptor and cyclin D1 are independently amplified and overexpressed in esophageal squamous cell carcinoma.

PURPOSE: To assess the status of EGFR, HER-2, and CCND1 at the gene and protein levels in esophageal squamous cell carcinoma. METHODS: Dual-color FISH assays were performed using DNA probes for EGFR/CEP 7, HER-2/CEP 17, and CCND1/CEP 11. The respective proteins, furthermore, was assessed in IHC assays and correlated with patient and tumor characteristics. RESULTS: From 55 ESCCs, 8 (15%) tumors showed gene amplification and 20 (36%) had gene overrepresentation (balanced gene and chromosome 7 polysomy) for EGFR. High-level protein expression was frequent (49%), positively correlated with gene copy numbers (kappa=0.4), and associated with well-differentiated histology (p=0.02). For HER-2, gene amplification was detected in a single tumor (2%) and protein overexpression was rare (9%). CCND1 gene was amplified in 23 (42%) tumors; likewise, CCND1 protein overexpression was common (58%) and prevailed in gene overrepresentation or amplification. Only 1 patient showed gene amplification for both EGFR and CCND1. Survival was not associated with EGFR or CCND1 gene/protein status, whereas negative patients for HER-2 protein had a better survival than positive patients (p=0.04). CONCLUSIONS: Frequent overexpression and gene amplification of EGFR and CCND1 make these molecules and their pathways potential therapeutic targets for ESCC. In addition, EGFR and CCND1 appeared to be independently altered suggesting alternative mechanisms for pathway activation. Therapeutic agents targeting these molecules are urged to be tested in clinical trials and comprehensive biological analyses should be included to properly interpret the outcome.

Isolated corneal intraepithelial neoplasia.

OBJECTIVES: To report two cases of isolated corneal intraepithelial neoplasia. MATERIAL AND METHOD: The present study included 2 cases presenting with isolated corneal intraepithelial neoplasia. Both patients were treated by corneal epithelial scraping. RESULTS: The authors present the clinical picture and histopathological findings of 2 patients suffering from corneal intraepithelial neoplasia that did not arise from the corneoscleral limbus. Both patients showed no recurrence after treatment for a period of time. CONCLUSION: Isolated corneal intraepithelial neoplasia is rare. Corneal scraping may be an effective treatment.