Winyou Mitarnun

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.

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

PurposeTo assess the status of EGFR, HER-2, and CCND1 at the gene and protein levels in esophageal squamous cell carcinoma.MethodsDual-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.ResultsFrom 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).ConclusionsFrequent 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.

Extranodal NK/T-cell lymphoma, nasal type, includes cases of natural killer cell and αβ, γδ, and αβ/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 &agr;&bgr; or &ggr;&dgr; 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 &ggr;&dgr; enteropathy-associated T-cell lymphomas (EATLs) for comparison. In all, 70% of the ENKTL were T-cell receptor (TCR) &bgr;,&ggr; and, in cases tested, &dgr; negative (presumptive NK origin); 5% were TCR &ggr;&dgr;+, 3% were TCR &agr;&bgr;+, 1% were TCR &agr;&bgr;/&ggr;&dgr;+, 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 &agr;&bgr; 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 &ggr;&dgr; 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 &ggr;&dgr; EATL.

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.

High tumor necrosis factor-α levels in the patients with Epstein–Barr virus-associated peripheral T-cell proliferative disease/lymphoma

We have attempted to find out any relationships between circulating tumor necrosis factor (TNF)-alpha levels and Epstein-Barr virus (EBV) associated peripheral T-cell and NK-cell proliferative disease/lymphoma (PTPD/L) status. The distribution of TNF-alpha level was significantly higher (P<0.05) in patients than in controls. Patients carrying EBV genome in their peripheral T-cells showed higher TNF-alpha levels than the patients with EBV negative peripheral T-cells (P<0.001). Among patients whose peripheral T-cells were positive for EBV genome, TNF-alpha levels between the wild type LMP-1 gene carriers and the 30-bp deletion type LMP-1 gene carriers were compared and the wild type LMP-1 gene carrier group showed significantly higher TNF-alpha levels (P<0.01). As for the outcome of the patients and TNF-alpha levels, significant differences were observed between dead and alive with disease group (P<0.001), and dead and alive with complete remission group (P<0.01). Since circulating TNF-alpha levels in PTPD/L patients correlate with the disease and EBV infection status, it may be possible that monitoring of the TNF-alpha levels will be a useful prognostic marker.

Non-fatal acute renal failure due to wasp stings in children

We report two children who developed acute renal failure after multiple wasp stings. Each case involved intravascular hemolysis which caused acute renal failure, volume overload, hypertension, anemia, hyponatremia, hyperkalemia, and metabolic acidosis. Peritoneal dialysis was required for short periods. The children recovered completely with blood urea nitrogen and creatinine returning to normal within 3 months. One child had a renal biopsy which showed mild tubulointerstitial nephritis. Although there is no specific treatment or antivenom, dialysis and supportive care have proved to be successful.

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. Students 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.

Tubulointerstitial renal failure in childhood leptospirosis.

We report three children with tubulointerstitial renal failure following leptospirosis. All had acute nonoliguric renal failure with mild hypocalemia and mild metabolic acidosis. Maximum blood urea nitrogen (BUN) and creatinine were 217 and 7.1 mg/dl, respectively, on the 6th day of disease, and no patient required dialysis. They presented with acute febrile illness and dehydration, and required intravenous fluid supplements. Myalgia, vomiting, and bleeding were found in two children. Abdominal pain, arthralgia, diarrhea, and conjunctival suffusion were found in one child. Only one child, who had an underlying disease of beta-thalassemia/Hb E, had jaundice, hepatosplenomegaly, anemia, and thrombocytopenia. Penicillin treatment was given in one case. All recovered, with normal renal function. The leptospirosis complement fixation test was used to confirm diagnosis. L. batavia was considered the etiologic agent in two of the children.

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.

Hepatic cytotoxic T-cell infiltrates in patients with peripheral T-cell proliferative diseases/lymphomas: Clinicopathological and molecular analysis

Seventy patients with various types of peripheral T‐cell proliferative disease/lymphoma who manifested with prolonged fever, weight loss, anemia, lymphadenopathy, hepatosplenomegaly and elevated serum levels of alkaline phosphatase and/or lactate dehydrogenase were evaluated. Histopathological examination of the livers revealed T‐cell infiltration into the hepatic sinusoids and portal tracts. The morphology of the infiltrated T cells varied from mature small lymphocytes to malignant lymphoid cells. The liver pathology was classified into four groups on the basis of cellular atypia. Group A and group B showed mature lymphoid cell infiltration; however, only group B had multiple large areas of hepatocellular necrosis. Group C showed atypical lymphoid cell infiltration and in group D malignant lymphoid cell infiltrates were demonstrated. The majority of the antigenic phenotypes of these T‐cell infiltrates were CD3+, CD4–, CD8+, CD20–, CD45RO+, CD56–, CD57–, TIA‐1+ and βF1–. Epstein–Barr virus RNA in the nuclei of the infiltrated T cells was recorded in 38.6% of the patients and was more common in groups C and D. Patients in groups B, C and D had a very poor prognosis, median survival was only 1 month, whereas median survival in group A patients was 36 months. Chemotherapy was not effective in improving survival.  Monoclonal  band/s  of  T‐cell  receptors  (TCR) β and/or γ gene rearrangements were detected in 88.6% of patients, and DNA‐sequence analysis showed high identity to the human TCR germline gene.