Biomedical subjects

Ponlapat Rojnuckarin

Publications and source records attributed to Ponlapat Rojnuckarin.

12 recordsLinked to original sources

PubMed2007

Severe beta(0) thalassemia/hemoglobin E disease caused by de novo 22-base pair duplication in the paternal allele of beta globin gene.

beta Thalassemia is a major public health concern in Southeast Asia. A prevention program has been implemented in Thailand comprising mass carrier screening and genetic testing. In this study, a Thai girl with severe beta thalassemia/hemoglobin (Hb) E disease was born from the mother with Hb E trait and the genotypically normal father. DNA sequencing revealed novel 22-bp tandem duplication in the paternal allele of beta globin gene, producing a severely truncated product. A short recurring nucleotide at the insertion site suggested a predisposition to this mutation. Therefore, spontaneous beta globin mutations occasionally occur in normal population. Its clinical significance is noteworthy in countries with high prevalence of beta thalassemia.

Alleles↗

PubMed2007

Utilization review of concomitant use of potentially interacting drugs in Thai patients using warfarin therapy.

PURPOSE: In Thailand, there has been no study determining the concomitant use of medications, known to potentially interact with warfarin, in patients receiving warfarin therapy. This paper examined the frequency of which specific interacting drugs were concomitantly used in warfarin users. METHODS: We retrospectively examined the database of warfarin outpatient medical records from a regional 756-bed hospital located in the north of Thailand. All patients receiving warfarin from 10 June 1999 to 4 August 2004 were reviewed to identify all drugs possessing interaction potential with warfarin. The potential of significant interactions were divided into high, moderate and low, according to the extent of evidence documented in textbooks and literature. RESULTS: Among 1093 patients receiving warfarin therapy, 914 (84%) patients received at least one potentially interacting drug and half of them (457 patients) received at least one drug with high potential for interaction. The most frequently concomitant drug that increased INR was acetaminophen (63%, 316/457). Propylthiouracil was the most frequently concomitant drug that decreased INR response (4%, 19/457), while diclofenac was the most frequently concomitant drug that increased bleeding risk (16%, 73/457). CONCLUSIONS: About a half of patients receiving warfarin therapy was prescribed concomitant drug(s) that has a high potential of interactions with warfarin. These patients should be closely monitored and counselled to watch for signs and symptoms of bleeding and thrombosis to avoid adverse events associated with drug interactions.

Acetaminophen↗

PubMed2006

A randomized, double-blind, placebo-controlled trial of antivenom for local effects of green pit viper bites.

Although systemic administration of antivenom can promptly reverse coagulopathy, efficacy on local effects of viper venom remains to be determined. Currently, there has been no proven specific treatment for snakebite patients with severe local effects. This study is a randomized, double-blind, placebo-controlled trial. Patients bitten by green pit vipers (Trimeresurus albolabris or T. macrops) with marked limb swelling, but no severe coagulopathy requiring antivenom, were randomized to receive either equine F(ab')2 antivenom, or placebo. Twenty-eight cases were included, 14 in each group, and they had their limb circumferences measured on days 1, 2, 4 and 6 after interventions. The percentage reduction in limb circumference was significantly better in the antivenom group compared with the placebo group (ANOVA, P = 0.03), especially in the first 24 h (1.14 vs. 3.62%, in placebo and antivenom group, respectively, P = 0.014). The reduction in pain score was similar. The plasma venom levels were not different at presentation but lower in the antivenom group 24h after intervention (P = 0.033). These data suggest that intravenous antivenom could accelerate local oedema resolution in humans. However, the degree is not clinically significant, and, therefore, general use is not recommended.

Adult↗

PubMed2006

Rituximab-CHOP-ESHAP vs CHOP-ESHAP-high-dose therapy vs conventional CHOP chemotherapy in high-intermediate and high-risk aggressive non-Hodgkin's lymphoma.

With currently available combination chemotherapy regimens, the outcome of the patients newly diagnosed with aggressive non-Hodgkin's lymphoma (NHL) identified as 'high' and 'high-intermediate' risk groups according to the international prognostic index (IPI) is still unsatisfactory and a more innovative therapy is urgently required to improve the survival of the patients. The purpose of this study was to compare the efficacy of rituximab given in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and ESHAP (etoposide, methylprednisolone, high-dose Ara-C, cisplatin) vs CHOP-ESHAP and upfront high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) vs standard CHOP in patients aged < or = 65 years old newly diagnosed with 'high' and 'high-intermediate' risk aggressive lymphoma enrolled onto two consecutive treatment trials at the institute. Between May 1995 - July 2002, 84 patients, aged 15 - 65 years old, with newly diagnosed aggressive NHL and an age-adjusted IPI of 2 or 3 were enrolled. The median age of the patients was 38 years (range 15 - 65). The baseline demographic features, in particular the major prognostic variables, were similar between the treatment groups. Patients treated with rituximab-CHOP-ESHAP received eight cycles of rituximab (375 mg m(-2) on day 1 of cycles 1 - 6 and days 21 and 28 of cycle 7) plus CHOP (day 3 of cycles 1, 3 and 5) and ESHAP (day 3 of cycles 2, 4 and 6 and day 1 of cycle 7) at 21-day intervals. Patients enrolled onto the CHOP-ESHAP-HDT arm (n = 23) were treated with three courses of CHOP and then switched to two or four cycles of ESHAP followed by HDT. Patients treated with CHOP alone (n = 25) were treated with the standard eight cycles of CHOP. The rate of complete remission was significantly improved with rituximab-CHOP-ESHAP compared with either CHOP-ESHAP-HDT or CHOP alone (67% compared with 44% and 36%, respectively; p = 0.043). With a median follow-up time of 53 months, the 5-year overall survival (OS) was improved by the addition of rituximab-61% with rituximab-CHOP-ESHAP, compared with 43% for CHOP-ESHAP-HDT and 24% for CHOP alone (p = 0.088). Significant increases in failure-free survival (FFS) and disease-free survival (DFS) (61% and 96%), compared with CHOP-ESHAP-HDT (34% and 90%) and CHOP (16% and 44%; p = 0.002 and p < 0.001, respectively) were observed. Compared to CHOP, rituximab-CHOP-ESHAP yielded significantly superior OS (p = 0.014), FFS (p < 0.001) and DFS (p < 0.001). The survivals, however, were not significantly different from patients treated with CHOP-ESHAP-HDT. It is concluded that rituximab-ESHAP-CHOP is superior over standard CHOP and fares comparably to upfront HDT/ASCT in previously untreated patients with aggressive lymphoma. A prospective randomized controlled trial is warranted to confirm these results.

Adolescent↗

PubMed2005

Molecular cloning of novel serine proteases and phospholipases A2 from green pit viper (Trimeresurus albolabris) venom gland cDNA library.

Green pit viper (Trimeresurus albolabris) is the most common venomous snake responsible for bites in Bangkok. It causes local edema and systemic hypofibrinogenemia resulted from the thrombin-like, as well as the fibrinolytic effects of the venom. However, the amino acid sequences of these venom proteins have never been reported. In this study, we have cloned five novel serine proteases from the Thai T. albolabris venom gland cDNA library. They were all closely homologous to the corresponding serine proteases from Chinese green viper (Trimeresurus stejnegeri), suggesting the evolutionary proximity of the two species. In addition, their functional activities could be deduced. There were predicted to be two thrombin-like enzymes (GPV-TL1 and GPV-TL-2), two isoforms of a fibrinogenolytic enzyme (albofibrase) and a plasminogen activator (GPV-PA), suggesting that defibrination syndrome in patients is a combination of these enzymatic effects. By multiple sequence alignment, no conserved residue or motif responsible for distinct functions of snake venom serine proteases could be observed. Moreover, one Lys 49 and one Asn 49 phospholipase A2 (PLA2) genes were cloned. Lys 49 PLA2 was predicted to devoid of catalytic activity, but showed a carboxy terminal cytotoxic region. No Asp 49 PLA2 was found in 150 clones screened. This explains the marked limb edema but no hemolysis in patients. These novel serine proteases have potentials to be therapeutic anti-thrombotic and thrombolytic agents in the future.

Animals↗

PubMed2005

Von Willebrand factor (vWF) antigen levels and function in healthy Thais.

Type I von Willebrand disease (vWD) is very common in caucasians. Its genetic basis is possibly heterogenous, lying both within and out of the vWF gene locus. We sought to investigate vWF levels in the Thai population, to compare with those of western countries. The vWF antigen and activity were measured using ELISA and Collagen Binding Assay (CBA), respectively, in 311 healthy Thai volunteers. The mean age was 32.3, ranging from 18 to 75 years. Fifty-four percent were female. Low vWF antigen and activity (below 50 U/dl) were found in 3.5% and 10.2%, respectively. Around 75% and 20% of these cases had O and A blood groups, respectively. Three (0.96%) had definitely low levels of vWF (vWF antigen level below 35 U/dl), suggesting the diagnosis of vWD. Similar to previous studies, vWF levels were lowest in subjects with group O blood. We found that subjects with blood group A had higher vWF levels than group O subjects, but significantly lower vWF levels than those with group B. The average ratio between the vWF activity and antigen was 0.96, ranging from 0.66 to 1.66. These ratios were inversely correlated with age (p=0.047), suggesting a decline in vWF activity per vWF protein with advancing age. Low levels of vWF are common in healthy Thais. Clinicians should be aware of vWD in bleeding patients and beware low levels of vWF in therapeutic plasma products, especially from blood groups O and A.

Adolescent↗

PubMed2005

Protein S deficiency is common in a healthy Thai population.

Currently, venous thromboembolism is a growing menace in Asians, approaching to that of Western countries. The most common genetic mutations causing thrombosis in Caucasians are factor V Leiden and prothrombin mutation. However both are very rare in Asians. On the other hand, natural anticoagulant protein (protein S, protein C and antithrombin) deficiencies are more common in Asian than in Western thrombotic patients. The prevalence of these deficiencies is very low in healthy Caucasians (0.02-0.3%). It is possible that the prevalence is higher in an Asian general population. However there have been very few prevalence studies to prove this hypothesis. Protein S deficiency was found in 3.7% (13/352, 95% confident interval 1.72-5.66) healthy Thais. Seven of them were type III deficiency. Similar to previous studies, total and free protein S levels were lower in females, but positively and negatively correlated with age, respectively. In contrast, one protein C deficiency (0.27%, 1/370) and no antithrombin deficiency (0/206) were detectable in our population. Furthermore, the authors found that antithrombin was significantly lower in women and there was a positive correlation between protein C activity and age. In conclusion, protein S deficiency is more common in Thais than in Caucasians. This result remains to be confirmed by a large population-based study.

Adolescent↗

PubMed2004

Mantle cell lymphoma in Thai patients.

Mantle cell lymphoma (MCL) is a disease entity recently introduced into the new lymphoma classification, therefore, the clinical features as well as therapeutic outcomes in Thai patients with MCL has never been described The authors herein retrospectively analysed 21 newly diagnosed patients with MCL at King Chulalongkorn Memorial Hospital from January 1997 to December 2002. The median age of the patients was 54 years (range, 38-79). Male:female was 4:1. Generalized lymphadenopathy (67%) was the most common presenting feature. The majority of patients (85%) had advanced disease (stage III, IV, Ann Arbor system). Fifty-six percent of the patients were classified as the high- and high-intermediate risk group by the international prognostic index. Most patients were treated with CHOP (vincristine, cyclophosphamide, doxorubicin, prednisolone) or CVP (vincristine, cyclophosphamide, prednisolone) regimen. The overall complete remission rate was 59%. With a median follow-up of 13 months (range, 1-62 months), the rates of overall, progression-free and disease-free survivals were 32%, 9% and 20%, respectively. Sixty-seven percent of the patients had relapse/progressive disease after follow-up. In conclusion, the clinical features as well as the outcomes of Thai patients with MCL were comparable to patients in Western countries. Newly diagnosed patients should be treated with novel modalities other than conventional CHOP chemotherapy in order to improve the outcomes.

Adult↗

PubMed2003

Recurring thrombocytopenia associated with structured treatment interruption in patients with human immunodeficiency virus infection.

In a structured treatment interruption (STI) trial, 3 of 23 patients in a CD4 cell count-guided treatment arm developed recurring thrombocytopenia associated with the interruption of antiretroviral therapy. All 3 patients had slightly low or normal platelet counts before initiating antiretroviral therapy. STI may play a role in inducing thrombocytopenia in patients with human immunodeficiency virus infection.

Adult↗

PubMed2003

Megakaryocytes require thrombospondin-2 for normal platelet formation and function.

Mice that lack the matricellular angiogenesis inhibitor, thrombospondin-2 (TSP2), display a bleeding diathesis, despite normal blood coagulation and the lack of thrombocytopenia. Although platelets do not contain detectable levels of TSP2, TSP2-null platelets are compromised in their ability to aggregate in vivo in response to denudation of the carotid artery endothelium, and in vitro following exposure to adenosine diphosphate (ADP). Megakaryocytes (MKs) show high levels of TSP2 by immunohistochemical analysis of bone marrow. However, when cultured in vitro, MKs contain little TSP2 protein or mRNA. These findings suggest that most TSP2 is acquired from the bone marrow microenvironment. Consistent with this hypothesis, MKs take up recombinant TSP2 in an integrin-dependent manner when it is supplied in the culture medium. Furthermore, uptake of TSP2 in vitro affects MK differentiation and proplatelet formation. The functional significance of this process is supported by the presence of ultrastructural abnormalities in TSP2-null bone marrow, including extensive fragmentation of the peripheral zone in MKs and failure of this zone to form close associations with vascular sinuses. We conclude that the uptake of TSP2 by MKs from the marrow milieu is required for proper MK function and the release of functionally competent platelets.

Animals↗

PubMed2003

Laboratory identification of lupus anticoagulants using the combination of activated partial thromboplastin time and Russell's viper venom at two phospholipid concentrations.

The most appropriate combination of tests for lupus anticoagulants (LA) is unknown. The standard double centrifugation method to prepare plasma was inadequate for platelet elimination, interfering with kaolin clotting time and mixing studies. In the present study, the percentage correction of activated partial thromboplastin time (APTT) and Russell's viper venom time (RVVT) by high compared with low concentrations of phospholipid was used for both screening and confirmation of LA. Abnormality in either one was reported as positive. The specificity of the tests in 122 individuals without LA was 100 per cent for RVVT and 96.7 per cent for APTT, which yielded false positive by heparin. The mixing study was omitted from the authors' strategy without decreasing the specificity. In 795 patients with thrombosis, LA was detectable in 6.03 per cent. The sensitivity of diluted activated partial thromboplastin time (dAPTT) and diluted Russell's viper venom time (dRVVT) alone, compared with the combination of the two was 83.3 per cent and 79.2 per cent respectively. Therefore, this new test scheme is a simple, inexpensive and efficient method for Thai patients.

Antiphospholipid Syndrome↗

PubMed2002

JAK2, complemented by a second signal from c-kit or flt-3, triggers extensive self-renewal of primary multipotential hemopoietic cells.

Defining signals that can support the self-renewal of multipotential hemopoietic progenitor cells (MHPCs) is pertinent to understanding leukemogenesis and may be relevant to developing stem cell-based therapies. Here we define a set of signals, JAK2 plus either c-kit or flt-3, which together can support extensive MHPC self-renewal. Phenotypically and functionally distinct populations of MHPCs were obtained, depending on which receptor tyrosine kinase, c-kit or flt-3, was activated. Self-renewal was abrogated in the absence of STAT5a/b, and in the presence of inhibitors targeting either the mitogen-activated protein kinase or phosphatidylinositol 3' kinase pathways. These findings suggest that a simple two-component signal can drive MHPC self-renewal.

Animals↗