Effects of land use configuration, seasonality and point source on water quality in a tropical watershed: A case study of the Johor River Basin.

Land use plays a significant role in determining the spatial patterns of water quality in the Johor River Basin (JRB), Malaysia. In the recent years, there have been several occurrences of pollution in these rivers, which has generated concerns over the long-term sustainability of the water resources in the JRB. Specifically, this water resource is a shared commodity between two states, namely, Johor state of Malaysia and Singapore, a neighbouring country adjacent to Malaysia. Prior to this study, few research on the influence of land use configuration on water quality have been conducted in Johor. In addition, it is also unclear how water quality varies under different seasonality in the presence of point sources. In this study, we investigated the influence of land use and point sources from wastewater treatment plants (WWTPs) on the water quality in the JRB. Two statistical techniques - Multivariate Linear Regression (MLR) and Redundancy Analysis (RA) were undertaken to analyse the relationships between river water quality and land use configuration, as well as point sources from WWTPs under different seasonality. Water samples were collected from 49 sites within the JRB from March to December in 2019. Results showed that influence from WWTPs on water quality was greater during the dry season and less significant during the wet season. In particular, point source was highly positively correlated with ammoniacal­nitrogen (NH3-N). On the other hand, land use influence was greater than point source influence during the wet season. Residential and urban land use were important predictors for nutrients and organic matter (chemical oxygen demand); and forest land use were important sinks for heavy metals but a significant source of manganese.

A two-in-one Janus NIR-II AIEgen with balanced absorption and emission for image-guided precision surgery.

Fluorescence imaging in the near-infrared II (NIR-II, 1000-1700 nm) region opens up new avenues for biological systems due to suppressed scattering and low autofluorescence at longer-wavelength photons. Nonetheless, the development of organic NIR-II fluorophores is still limited mainly due to the shortage of efficient molecular design strategy. Herein, we propose an approach of designing Janus NIR-II fluorophores by introducing electronic donors with distinct properties into one molecule. As a proof-of-concept, fluorescent dye 2 TT-m, oC6B with both twisted and planar electronic donors displayed balanced absorption and emission which were absent in its parent compound. The key design strategy for Janus molecule is that it combines the merits of intense absorption from planar architecture and high fluorescence quantum yield from twisted motif. The resulting 2 TT-m, oC6B nanoparticles exhibit a high molar absorptivity of 1.12 ⨯104 M-1 cm-1 at 808 nm and a NIR-II quantum yield of 3.7%, displaying a typical aggregation-induced emission (AIE) attribute. The highly bright and stable 2 TT-m, oC6B nanoparticles assured NIR-II image-guided cancer surgery to resect submillimeter tumor nodules. The present study may inspire further development of molecular design philosophy for highly bright NIR-II fluorophores for biomedical applications.

A framework for assessing the adequacy of Water Quality Index - Quantifying parameter sensitivity and uncertainties in missing values distribution.

Water quality monitoring is a pillar in water resource management, but it can be resource intensive, especially for developing countries with limited resources. As such, Water Quality Indices (WQI) are developed to summarise general water quality, but efforts to assess the utility, flexibility, and practicality of WQI have been limited. In this study, we introduced an additional step to the traditional WQI development framework by introducing an adjusted form of WQI (WQIADJUSTED) to handle missing values, and capitalise on the remaining available information for the development of a WQI. A Sub-WQI was also developed to address local water quality conditions. WQI results (weighted and non-weighted) developed using different parameter optimisation methods, namely Multivariate Linear Regression and Principal Component Analysis were compared. To build upon the current framework, a new procedure was developed to assess the adequacy of WQI based on the sensitivity analysis of parameters and uncertainties associated with each parameter's missing values distribution. The number of observations needed for the development of a robust WQI was optimised with respect to user-defined acceptable change in WQI, based on Monte Carlo probabilistic simulation. The Johor River Basin (JRB), Malaysia is used as a case-study for the application of this new framework. The JRB serves as an important resource for Johor, one of the most populous state in Malaysia, and Singapore, a country south of Johor. WQIMLR performed better in explaining the general water quality than WQIPCA for weighted water quality parameters. Optimisation of sampling frequency revealed that around 130 samples will be required if a 2% change in WQI can be tolerated. The results (specific to the JRB) also revealed that total coliform is the most sensitivity parameter to missing values, and the distribution of sensitive parameters are similar for both WQINON-ADJUSTED and WQIADJUSTED.

Pre-closure assessment of elevated arsenic and other potential environmental constraints to developing aquaculture and fisheries: The case of the Mae Moh mine and power plant, Lampang, Thailand.

Our assessment of 30 water bodies in the vicinity of the Mae Moh coal mine and power station in northern Thailand does not indicate substantial water quality management challenges to developing fisheries/aquaculture in peripheral reservoirs and streams. Negative water quality issues such as high concentrations of arsenic (2-17 µg/L) and ions including sulfate (868-2605 mg/L), sodium (217-552 mg/L), and total ammonia (<1-5 mg/L) were associated with groundwater and surface water resources on the facility, as well as the stream network draining from it. Total dissolved solids were also very high, ranging from 658 to 3610 mg/L. Six of seven ponds tested had As concentrations in the range of 5-17 µg/L. Although these levels are less than the Thai regulation for industrial effluent, they are elevated over background surface water concentrations. The highest concentration in a contaminated stream was 10.54 µg/L As, which is only slightly above the WHO (2017) regulation of 10 µg/L for drinking water. Ponds, contaminated streams, and deep subsurface water should not be used for fisheries/aquaculture without extensive remediation/treatment. Concentrations of these water parameters in peripheral streams and reservoirs were not of environmental concern. High water hardness (161-397 mg/L CaCO3 and potential ionic imbalances may be the greatest hindrances to developing sustainable fisheries and aquaculture in reservoirs in the study area. Routine monitoring of inorganic As species and other contaminants in water is needed to assess the full extent of arsenic risk at the site following closure.

Water Use by Inland Aquaculture in Thailand: Stakeholder Perceptions, Scientific Evidence, and Public Policy.

This paper assesses the significance of stakeholder discourses on uses of water by aquaculture for public policy. Our discourse analysis focuses on the experiences with inland aquaculture in Thailand, drawing from interviews with stakeholders, and evidence in public documents such as newspapers and television news reports. A key finding is that fish farms suffer significant losses from polluted run-off entering water bodies where fish are grown. Mass mortality events in river cage culture, in particular, attract media attention and are the core of the aquaculture-as-victim discourse. Fish farms are also adversely impacted by river management and current water allocation policies. Inland shrimp farming has received more negative media and scientific attention than fish farming, and is the focus of the aquaculture-as-villain discourse. A third, aquaculture-as-benign discourse, is used widely to describe fish pond culture, and more rarely to promote aquaculture in low-quality water bodies or as part of integrated nutrient and waste re-use farming systems. The findings strongly imply that aquaculture farmers should be included as a stakeholder in the management of watersheds and rivers, as well as the negotiation and allocation of water resources. They also suggest a need for aquaculture development policies to pay closer attention to water quality and allocation issues.

Real-world Effectiveness and Safety of Vedolizumab for the Treatment of Inflammatory Bowel Disease: The Scottish Vedolizumab Cohort.

BACKGROUND & AIMS: Vedolizumab is an anti-a4b7 monoclonal antibody that is licensed for the treatment of moderate to severe Crohn's disease and ulcerative colitis. The aims of this study were to establish the real-world effectiveness and safety of vedolizumab for the treatment of inflammatory bowel disease. METHODS: This was a retrospective study involving seven NHS health boards in Scotland between June 2015 and November 2017. Inclusion criteria included: a diagnosis of ulcerative colitis or Crohn's disease with objective evidence of active inflammation at baseline (Harvey-Bradshaw Index[HBI] ≥5/Partial Mayo ≥2 plus C-reactive protein [CRP] >5 mg/L or faecal calprotectin ≥250 µg/g or inflammation on endoscopy/magnetic resonance imaging [MRI]); completion of induction; and at least one clinical follow-up by 12 months. Kaplan-Meier survival analysis was used to establish 12-month cumulative rates of clinical remission, mucosal healing, and deep remission [clinical remission plus mucosal healing]. Rates of serious adverse events were described quantitatively. RESULTS: Our cohort consisted of 180 patients with ulcerative colitis and 260 with Crohn's disease. Combined median follow-up was 52 weeks (interquartile range [IQR] 26-52 weeks). In ulcerative colitis, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 57.4%, 47.3%, and 38.5%, respectively. In Crohn's disease, 12-month cumulative rates of clinical remission, mucosal healing, and deep remission were 58.4%, 38.9%, and 28.3% respectively. The serious adverse event rate was 15.6 per 100 patient-years of follow-up. CONCLUSIONS: Vedolizumab is a safe and effective treatment for achieving both clinical remission and mucosal healing in ulcerative colitis and Crohn's disease.

Temporal Variability of Faecal Contamination from On-Site Sanitation Systems in the Groundwater of Northern Thailand.

We investigated the impacts of on-site sanitation systems to local groundwater. In this year-long study, we monitored the response of faecal contamination levels to hydroclimatological factors including rainfall and groundwater table. Concentration of faecal indicators-E. coli (ESC), Enterococcus (ENT), nitrate-in thirteen pairs of shallow and deep wells were determined every 7-14 days. All samples from shallow wells were tested positive for faecal contamination (ESC and ENT > 1 MPN/100 mL) but concentration varies. A maximum of 24,000 MPN/100 mL were recorded in some shallow wells. Water from deep wells showed lower susceptibility to contamination with only 4 and 23% of samples tested positive for ESC and ENT, respectively. Concentrations of ESC and ENT were lower too, with a maximum of 5 MPN/100 mL and 28 MPN/100 mL, respectively. Fluctuation in contamination among the wells was described by four archetypal responses to hydroclimatological forcing: (i) flushing during the onset of wet season, (ii) dilution over the course of the wet season, (iii) concentration during the dry season, and (iv) synoptic response to storms. Previous studies attempting to link the prevalence of faecal/waterborne diseases and temporal factors (e.g., dry vs wet season) have produced differing outcomes. Our study may help explain the relevant hydrological mechanisms leading to these varying observations. Presently, most communities in Thailand have access to 'improved' sanitation systems. However, due to the unsustainable implementation of these systems, the otherwise viable drinking-water resources in the form of the abundant local groundwater has become a genuine health hazard.

Hydrological connectivity and Burkholderia pseudomallei prevalence in wetland environments: investigating rice-farming community's risk of exposure to melioidosis in North-East Thailand.

In our analysis of 136 water samples from wetland environments (rice paddies, natural wetland sites, man-made water bodies) in rural areas of North-East Thailand, Burkholderia pseudomallei was most prevalent in rice paddies (15 of the 30 positive sites). The high prevalence in the water of rice fields is indicative of the inherent vulnerability of farmers in rural agricultural areas in this area of Thailand and likely other locations in the tropics. Nearly all B. pseudomallei-positive sites were found within the vicinity of a large wetland associated with the Chi River, in the month of July 2014. Positive samples were found in water ranging in pH from 5.9 to 8.7, salinity ranging from 0.04 to 1.58 ppt, nitrate ranging from 0 to 10.8 ppm, and iron ranging from 0.003 to 1.519 ppm. Of these variables, only iron content was statistically higher in B. pseudomallei-positive versus B. pseudomallei-negative sites, suggesting that increasing concentrations of iron may encourage the growth of this bacterium, which is responsible for melioidosis. Our results, when combined with data from other published studies, support the notion that B. pseudomallei can exist in a wide range of environmental conditions. Thus, we argue that health safety education is a more appropriate means of addressing farmer vulnerability than chemical or physical alterations to fields at large scales. Further, it may be important to investigate melioidosis through transdisciplinary approaches that consider the complex social and ecological contexts in which the disease occurs.

Prevalence of Cryptosporidium and Giardia in the water resources of the Kuang River catchment, Northern Thailand.

A catchment-scale investigation of the prevalence of Cryptosporidium and Giardia in the Kuang River Basin was carried out during the dry and rainy seasons. Water samples were collected from the Kuang River and its tributaries as well as a major irrigation canal at the study site. We also investigated the prevalence of gastrointestinal parasitic infection among dairy and beef cattle hosts. Cryptosporidium and/or Giardia were detected in all the rivers considered for this study, reflecting their ubiquity within the Kuang River Basin. The high prevalence of Cryptosporidium/Giardia in the upper Kuang River and Lai River is of a particular concern as both drain into the Mae Kuang Reservoir, a vital source of drinking-water to many local towns and villages at the research area. We did not, however, detected neither Cryptosporidium nor Giardia were in the irrigation canal. The frequency of Cryptosporidium/Giardia detection nearly doubled during the rainy season compared to the dry season, highlighting the importance of water as an agent of transport. In addition to the overland transport of these protozoa from their land sources (e.g. cattle manure, cess pits), Cryptosporidium/Giardia may also be re-suspended from the streambeds (a potentially important repository) into the water column of rivers during storm events. Faecal samples from dairy and beef cattle showed high infection rates from various intestinal parasites - 97% and 94%, respectively. However, Cryptosporidium and Giardia were only detected in beef cattle. The difference in management style between beef (freeranging) and dairy cattle (confined) may account for this disparity. Finally, phylogenetic analyses revealed that the Cryptosporidium/Giardia-positive samples contained C. ryanae (non-zoonotic) as well as Giardia intestinalis assemblages B (zoonotic) and E (non-zoonotic). With only basic water treatment facilities afforded to them, the communities of the rural area relying on these water supplies are highly at risk to Cryptosporidium/Giardia infections.

Untangling the Complexity of Liver Fluke Infection and Cholangiocarcinoma in NE Thailand Through Transdisciplinary Learning.

This study demonstrates how a transdisciplinary learning approach provided new insights for explaining persistent Opisthorchis viverrini infection in northern Thailand, as well as elucidating problems of focusing solely on the parasite as a means of addressing high prevalence of cholangiocarcinoma. Researchers from diverse backgrounds collaborated to design an investigative homestay program for 72 Singaporean and Thai university students in five northeast Thai villages. The students explored how liver fluke infection and potential cholangiocarcinoma development are influenced by local landscape dynamics, aquatic ecology, livelihoods, food culture and health education. Qualitative fieldwork was guided daily by the researchers in a collaborative, co-learning process that led to viewing this health issue as a complex system, influenced by interlinked multidimensional factors. Our transdisciplinary experience has led us to believe that an incomplete understanding of these linkages may reduce the efficacy of interventions. Further, viewing liver fluke infection and cholangiocarcinoma as the same issue is inadvisable. Although O. viverrini infection is an established risk factor for the development of cholangiocarcinoma, multiple factors are known to influence the likelihood of acquiring either. Understanding the importance of the current livelihood transition, landscape modification and the resulting mismatch between local cultures and new socio-ecological settings on cholangiocarcinoma initiation and liver fluke transmission is of critical importance as it may help readjust our view of the respective role of O. viverrini and other socioeconomic risk factors in cholangiocarcinoma etiology and refine intervention strategies. As demonstrated in this study, transdisciplinary approaches have the potential to yield more nuanced perspectives to complex diseases than research that focuses on specific aspects of their epidemiology. They may therefore be valuable when designing effective solutions to context-sensitive diseases such as liver fluke infection and cholangiocarcinoma.

Fluoride: A naturally-occurring health hazard in drinking-water resources of Northern Thailand.

In Northern Thailand, incidences of fluorosis resulting from the consumption of high-fluoride drinking-water have been documented. In this study, we mapped the high-fluoride endemic areas and described the relevant transport processes of fluoride in enriched waters in the provinces of Chiang Mai and Lamphun. Over one thousand surface and sub-surface water samples including a total of 995 collected from shallow (depth: ≤ 30 m) and deep (> 30 m) wells were analysed from two unconnected high-fluoride endemic areas. At the Chiang Mai site, 31% of the shallow wells contained hazardous levels (≥ 1.5 mg/L) of fluoride, compared with the 18% observed in the deep wells. However, at the Lamphun site, more deep wells (35%) contained water with at least 1.5mg/L fluoride compared with the shallow wells (7%). At the Chiang Mai site, the high-fluoride waters originate from a nearby geothermal field. Fluoride-rich geothermal waters are distributed across the area following natural hydrological pathways of surface and sub-surface water flow. At the Lamphun site, a well-defined, curvilinear high-fluoride anomalous zone, resembling that of the nearby conspicuous Mae Tha Fault, was identified. This similarity provides evidence of the existence of an unmapped, blind fault as well as its likely association to a geogenic source (biotite-granite) of fluoride related to the faulted zone. Excessive abstraction of ground water resources may also have affected the distribution and concentration of fluoride at both sites. The distribution of these high-fluoride waters is influenced by a myriad of complex natural and anthropogenic processes which thus created a challenge for the management of water resources for safe consumption in affected areas. The notion of clean and safe drinking water can be found in deeper aquifers is not necessarily true. Groundwater at any depth should always be tested before the construction of wells.

Bilineal T lymphoblastic and myeloid blast transformation in chronic myeloid leukemia with TP53 mutation-an uncommon presentation in adults.

Bilineal blast transformation of myeloid and T lymphoid type is a rare event in chronic myeloid leukemia. Here, we report a case in which an adult presented with high white cell counts and lymphadenopathy. Bone marrow studies confirmed the presence of 9 and 22 chromosomal translocation, and a diagnosis of chronic myeloid leukemia in chronic phase was made. Examination of a lymph node showed both myeloid and T lymphoblastoid blast crisis. Molecular studies demonstrated the presence of BCR-ABL fusion transcripts in both the myeloid and the T lymphoblastic component, indicating that the myeloid and T lymphoid blast crisis components shared common progenitors. TP53 deletion was demonstrated by fluorescence in situ hybridization.

A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias.

BACKGROUND: Ponatinib is a potent oral tyrosine kinase inhibitor of unmutated and mutated BCR-ABL, including BCR-ABL with the tyrosine kinase inhibitor-refractory threonine-to-isoleucine mutation at position 315 (T315I). We conducted a phase 2 trial of ponatinib in patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). METHODS: We enrolled 449 heavily pretreated patients who had CML or Ph-positive ALL with resistance to or unacceptable side effects from dasatinib or nilotinib or who had the BCR-ABL T315I mutation. Ponatinib was administered at an initial dose of 45 mg once daily. The median follow-up was 15 months. RESULTS: Among 267 patients with chronic-phase CML, 56% had a major cytogenetic response (51% of patients with resistance to or unacceptable side effects from dasatinib or nilotinib and 70% of patients with the T315I mutation), 46% had a complete cytogenetic response (40% and 66% in the two subgroups, respectively), and 34% had a major molecular response (27% and 56% in the two subgroups, respectively). Responses were observed regardless of the baseline BCR-ABL kinase domain mutation status and were durable; the estimated rate of a sustained major cytogenetic response of at least 12 months was 91%. No single BCR-ABL mutation conferring resistance to ponatinib was detected. Among 83 patients with accelerated-phase CML, 55% had a major hematologic response and 39% had a major cytogenetic response. Among 62 patients with blast-phase CML, 31% had a major hematologic response and 23% had a major cytogenetic response. Among 32 patients with Ph-positive ALL, 41% had a major hematologic response and 47% had a major cytogenetic response. Common adverse events were thrombocytopenia (in 37% of patients), rash (in 34%), dry skin (in 32%), and abdominal pain (in 22%). Serious arterial thrombotic events were observed in 9% of patients; these events were considered to be treatment-related in 3%. A total of 12% of patients discontinued treatment because of an adverse event. CONCLUSIONS: Ponatinib had significant antileukemic activity across categories of disease stage and mutation status. (Funded by Ariad Pharmaceuticals and others; PACE ClinicalTrials.gov number, NCT01207440 .).

Biological properties of sodium alkyl methyl ester sulfonate/alkyltrimethylammonium bromide surfactant mixtures.

Quaternary ammonium compounds (QACs) are commonly used as disinfectant in medical care, food industry, detergents and glue industries. This is due to a small concentration of QACs is sufficient to inhibit the growth of various bacteria strains. In this work, the inhibitive power of cationic surfactants, alkyltrimethylammonium bromide (C(n)TAB) in the presence of anionic surfactants, sodium alkyl methyl ester α-sulfonate (C(n)MES) was studied. The growth inhibition test with gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria were used to determine the toxicity of single and mixed surfactants. Results from this work showed that certain mixed surfactants have lower minimum inhibition concentration (MIC) as compared to the single C(n)TAB surfactants. Besides that, it was also found that alkyl chain length and the mixing ratios of the surfactants play a significant role in determining the mixture inhibitive power.

Attainment of at least a very good partial response after induction treatment is an important surrogate of longer survival for multiple myeloma.

The importance of achieving a very good partial response or better (≥VGPR) after induction treatment of myeloma has traditionally only been discussed in the context of high-dose therapy with auto-SCT (HDT/auto-SCT). Of late, the advent of novel agents for induction treatment has resulted in improved CR and VGPR rates, which are comparable with those observed with HDT/auto-SCT. We show that in an unselected group of 179 myeloma patients with diverse baseline characteristics, and treated with different modern induction regimens within a single institution, the attainment of ≥VGPR with or without HDT/auto-ASCT represents a major surrogate marker of better clinical outcomes. On the basis of a 1-year landmark survival analysis, patients achieving ≥VGPR enjoy a significantly longer PFS, which translated to a longer OS. Superseding the adverse effects of advanced age, high International Staging System (ISS) stage, adverse cytogenetics and independent of the transplant status, the attainment of ≥VGPR emerged as the single most significant predictor of long-term survival on multivariate analysis.

Stem cell transplantation programme at Singapore General Hospital.

The adult transplant programme at Singapore General Hospital (SGH) was established in 1985 and more than 820 transplants have been performed to date. An average of about 60 adult transplants (autologous and allogeneic) are performed each year. Transplants offered at SGH run the range from autologous to mismatched cord and unrelated transplants. Special interests of the transplant programme include non-myeloablative transplants in aplastic anaemia, cell therapy protocols including cytokine-induced killer cells, patterns of GVHD, cord blood transplantation for autoimmune diseases and graft engineering. A cGMP (good manufacturing practice) cell therapy laboratory was recently established to facilitate bench-to-bedside translational cell therapy trials. A BMT consortium has been formed among the various paediatric and adult transplant centres for harmonization of protocols and research activities.

Pseudoretinoblastoma in enucleated eyes of Asian patients.

INTRODUCTION: Retinoblastomas of the eye are a cause of childhood blindness and have a high rate of mortality, as well as a hereditary mode of transmission. Other conditions that mimic retinoblastomas are known as pseudoretinoblastomas, and are managed differently. Although pseudoretinoblastoma and the accuracy of retinoblastoma diagnosis have been reviewed in Caucasian patients, published studies in Asian patients are lacking. The purpose of this article is to report our experience with pseudoretinoblastomas in two major ophthalmological centres in Asia. METHODS: A case series of 28 enucleations carried out for suspected retinoblastoma at the Singapore National Eye Centre and KK Women's and Children's Hospital, Singapore, between January 1991 and December 2002, is reported. All cases were subjected to a detailed history from parents, followed by external ocular examination, slit-lamp biomicroscopy and binocular indirect ophthalmoscopy. Ancillary studies, such as B-scan ultrasonography and computed tomography, were employed as necessary to confirm the diagnosis. Histology was obtained on all cases. RESULTS: Of the 28 cases, 25 (89 percent) were found on histological analysis to be retinoblastomas. Three (11 percent) were pseudoretinoblastomas. There were two cases of Coat's disease and a case of presumed ocular toxocariasis. These three cases were described in detail. CONCLUSION: Although our sample size is small, the percentage of confirmed retinoblastomas was found to be only slightly higher than that found in western countries. Our findings are consistent with their findings that Coat's disease and presumed ocular toxocariasis are the more common causes of pseudoretinoblastoma.

Zoledronate inhibits proliferation and induces apoptosis of imatinib-resistant chronic myeloid leukaemia cells.

Although imatinib mesylate has revolutionized the treatment of chronic myeloid leukaemia (CML), resistance to the drug, manifesting as relapse after an initial response or persistence of disease, remains a therapeutic challenge. In order to overcome this, alternative or additional targeting of signaling pathways downstream of Bcr-Abl may provide the best option for improving clinical response. Bisphosphonates, such as zoledronate, have been shown to inhibit the oncogenicity of Ras, an important downstream effector of Bcr-Abl. In this study, we show that zoledronate is equally effective in inhibiting the proliferation and clonogenicity of both imatinib-sensitive and -resistant CML cells, regardless of their mechanism of resistance. This is achieved by the induction of S-phase cell cycle arrest and apoptosis, through the inhibition of prenylation of Ras and Ras-related proteins by zoledronate. The combination of imatinib and zoledronate also augmented the activity of either drug alone and this occurred in imatinib-resistant CML cells as well. Since zoledronate is already available for clinical use, these results suggest that it may be an effective addition to the armamentarium of drugs for the treatment of CML.

Integrated hydroxyapatite implant and non-integrated implants in enucleated Asian patients.

INTRODUCTION: This study compares the outcome and complications of integrated hydroxyapatite implant and non-integrated orbital implants following enucleation in Asian patients. MATERIALS AND METHODS: This is a retrospective study of enucleated patients with coralline hydroxyapatite implants versus non-integrated implants (acrylic, glass and silicone) at the Singapore National Eye Centre from January 1991 to December 2000. The outcomes measured were implant migration, extrusion, socket infection, conjunctival dehiscence and implant exposure. Statistical analysis was done using the 2-sample t-test. RESULTS: Twenty-one patients had the hydroxyapatite implant and 38 non-integrated implants (27 acrylic, 9 glass and 2 silicone). The mean duration of follow-up was 2.7 years and 4 years for the hydroxyapatite implant and non-integrated implants respectively. Three patients with pre-existing severe socket contracture before enucleation surgeries were excluded from the study. Four cases of implant migration, 4 cases of implant extrusion and 3 cases of socket infection were encountered; all were sockets fitted with non-integrated implants. There was a higher rate of conjunctival dehiscence for sockets with hydroxyapatite implants (6 out of 21) compared to sockets with non-integrated implants (3 out of 35). This was statistically significant (P = 0.048). CONCLUSIONS: Implant complications of migration, extrusion and socket infection were found in non-integrated implants and none in coralline hydroxyapatite implants, which had a significantly higher rate of conjunctival dehiscence. Most of these were easily managed with only a small number progressing to implant exposure.