Endoscopic sphincterotomy with balloon dilatation versus sphincterotomy alone for common bile duct stones removal: a randomised controlled trial.

INTRODUCTION: Endoscopic sphincterotomy (EST) plus endoscopic papillary large balloon dilatation (EPLBD) has been reported as a valid alternative to EST alone in removing common bile duct (CBD) stone. The aim of this study is to compare efficacy, and safety of these two groups of patients in removing CBD stone in Hospital Universiti Sains Malaysia (HUSM). MATERIALS AND METHODS: This is a prospective single centre randomised single blinded comparative study conducted in HUSM. The primary endpoints for this study are the overall complete stone clearance rate and complication rate, while the secondary outcome for this study are duration of procedure and rate of usage of adjunct methods. Objective data analysis is conducted using independent sample t-test and chi-squared test. RESULTS: A total of 66 patients underwent endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis which is CBD stone. 34 patients were allocated to EST plus EPLBD arm (n=34), and 32 patients were in EST alone arm (n=32) using randomisation method. For intention to treat, patients from EST alone arm that unable to achieve complete stone clearance will be switched to EST plus EPLBD arm. The overall complete stone removal rate for both groups were comparable (EST plus EPLDB: 100% versus EST alone: 93.8%; p= 0.139). The two patients from EST alone group (6.2%) that unable to achieve complete stone clearance were converted to EST plus EPLBD group for intention to treat and able to achieve complete stone clearance by EST plus EPLBD. For procedural time, both arms are comparable as well (EST plus EPLDB: 15.8 minutes vs EST alone: 15.5 minutes; p= 0.860). Complications such as pancreatitis occurred in one patient in EST plus EPLBD arm (EST plus EPLDB: 2.9 % vs EST alone: 0 %; p= 0.328), and bleeding occurred in one patient in EST alone arm (EST plus EPLDB: 0 % vs EST alone: 3.1 %; p= 0.299) , but it is not statistically significant. No perforation or cholangitis complication occurred in both groups. No adjunct usage was observed in both groups. CONCLUSION: In this study with limited sample size, both EST plus EPLBD and EST alone are effective and has comparable procedural time in removing CBD stone. Even though both methods are equally effective, EPLBD plus EST is an alternative solution if complete stone clearance is unable to achieve via EST alone.

The effect of hypoxic ischemic encephalopathy towards multi-organ complications and its early outcome at a Malaysian district hospital.

INTRODUCTION: Hypoxic ischemic encephalopathy (HIE) is a clinically defined syndrome of disturbed neurologic function in the newborn with evidence of perinatal asphyxia. Stages of HIE are categorised into mild, moderate or severe based on the Sarnat classification. Neurological dysfunction constitutes a part of the wide spectrum of hypoxic ischemic insult as affected infants can have co-existing multi-organ dysfunction which further contributes to morbidities and mortality. This study aims to determine the relationship between the severity of HIE with multi-organ complications and early clinical outcomes. MATERIALS AND METHODS: All neonates who were admitted to the NICU at Hospital Sultan Abdul Halim between January 2018 to December 2022, who fulfilled the inclusion criteria were included. Demographic data, clinical course and investigation results were retrospectively obtained from the medical records. RESULTS: From a total of 90 infants (n = 90) who fulfilled our inclusion criteria, 31 (34%) were mild, 31 (34%) were moderate and 28 (31%) were severe HIE. The mean maternal age was 27 years. Common antenatal issues include diabetes mellitus (37.8%) and anaemia (22.2%). The Apgar scores at 1 and 5 minutes, initial resuscitation requiring intubation, chest compression and adrenaline were associated with higher severity of HIE (p < 0.05). Coagulation dysfunction was the most common complication (79.7%), followed by respiratory dysfunction (33.3%), cardiac dysfunction (28.9%), renal dysfunction (16.1%), haematological dysfunction (15.6%) and hepatic dysfunction (12%). Respiratory and haematological dysfunctions were significantly associated with higher mortality (p < 0.05). There was a significant longer hospital stay (p = 0.023), longer duration of ventilation (p < 0.001) and increase in frequency of seizures (p < 0.001) when comparing moderate and severe HIE patients to mild HIE patients. With increasing severity of HIE, there was also statistically significant higher mortality (p < 0.001). CONCLUSIONS: There is a significant relationship between multiorgan dysfunction, the severity of HIE and mortality. Early anticipation of multi-organ injury is crucial for optimal early management which would reduce the mortality and improve the neurological outcome of the patients.

Clinical outcomes of acute stroke thrombolysis in neurologist and non-neurologist centres - A comparative study in Malaysia.

BACKGROUND: Thrombolytic therapy with intravenous alteplase is a well-established treatment for acute ischaemic stroke (AIS). However, in Malaysia, treatment prescription is often limited by the availability of neurologists. The objective was to compare the outcomes of acute stroke thrombolysis therapy prescribed by neurologists in the Seberang Jaya Hospital (SJH) and non-neurologists in the Taiping Hospital (TH). METHODS: In this cross-sectional study, all AIS patients who received thrombolytic therapy in SJH and TH between January 2012 and September 2019 were included. Clinical data was extracted from admission records. The outcomes assessed were the percentage of patients who achieved excellent functional outcome at 3 months (modified Rankin scale of 0 to 1), rates of symptomatic intracranial haemorrhage (SICH), and mortality. RESULTS: A total of 63 AIS patients who received thrombolytic therapy were included, of which 37 patients (58.7%) were treated in SJH. The median NIHSS on admission was 12 in SJH and 11.5 in TH. In all 21.6% of patients from SJH and 30.7% of patients from TH achieved favourable functional outcome at 3 months (p=0.412). There were no significant differences between the two centres in terms of the rates of SICH (10.8% in SJH and 3.8% in TH, p=0.314) and 3-month mortality (24.3% versus 12.5%, p=0.203). CONCLUSION: The 3-month functional outcomes and complication rates of stroke thrombolysis in hospitals with or without neurologists are not significantly different. Thus non-neurologist hospitals may be able to provide thrombolysis service to AIS patients safely and effectively.

Treatment of supragastric belching with cognitive behavioral therapy improves quality of life and reduces acid gastroesophageal reflux.

OBJECTIVES: Excessive supragastric belching (SGB) manifests as troublesome belching, and can be associated with reflux and significant impact on quality of life (QOL). In some GERD patients, SGB-associated reflux contributes to up to 1/3 of the total esophageal acid exposure. We hypothesized that a cognitive-behavioral intervention (CBT) might reduce SGB, improve QOL, and reduce acid gastroesophageal reflux (GOR). We aimed to assess the effectiveness of CBT in patients with pathological SGB. METHODS: Patients with SGB were recruited at the Royal London Hospital. Patients attended CBT sessions focused on recognition of warning signals and preventative exercises. Objective outcomes were the number of SGBs, esophageal acid exposure time (AET), and proportion of AET related to SGBs. Subjective evaluation was by patient-reported questionnaires. RESULTS: Of 51 patients who started treatment, 39 completed the protocol, of whom 31 had a follow-up MII-pH study. The mean number of SGBs decreased significantly after CBT (before: 116 (47-323) vs. after 45 (22-139), P<0.0003). Sixteen of 31 patients were shown to have a reduction in SGB by >50%. In patients with increased AET at baseline, AET after CBT was decreased: 9.0-6.1% (P=0.005). Mean visual analog scale severity scores decreased after CBT (before: 260 (210-320) mm vs. after: 140 (80-210) mm, P<0.0001). CONCLUSIONS: Cognitive behavioral therapy reduced the number of SGB and improved social and daily activities. Careful analysis of MII-pH allows identification of a subgroup of GERD patients with acid reflux predominantly driven by SGB. In these patients, CBT can reduce esophageal acid exposure.

Discordance of patient and physician health status concerns in systemic lupus erythematosus.

Objectives To compare the health status concerns of patients with systemic lupus erythematosus (SLE) and of their physicians. Methods Cross-sectional questionnaire study of SLE patients and their treating physicians at a tertiary disease-specific outpatient clinic. Patients and physicians completed a questionnaire regarding their concern about specific disease manifestations and impact on quality of life. For each item, degree of concern was rated on a five-point Likert scale and summarized as median (interquartile range). Ratings between patients and physicians were compared using Mann-Whitney U tests. Results A total of 84 patients and 21 physicians participated. Patients' predominant concerns centred on function and fatigue, whereas physicians' concerns focused on SLE-related organ complications. Of the 10 highest ranked patient concerns, only two were common to the 10 highest ranked physician concerns, while physicians rated seven significantly differently; all 10 highest ranked physician concerns were rated significantly lower by patients. The three highest ranked patient concerns (fatigue, pain and feeling worn out) were routinely assessed by 47.6%, 42.9% and 9.5% of physicians, respectively. Conclusion There was significant discordance between SLE patient and physician health status concerns. Items which were ranked highly by patients were not assessed consistently by physicians, highlighting a significant gap in healthcare communication.

Intestinal tuberculosis: a diagnostic challenge.

OBJECTIVE: To describe characteristics, presentation, time to diagnosis and diagnostic findings of patients with intestinal tuberculosis (ITB) in a low-burden country. METHOD: Retrospective study of 61 consecutive ITB patients diagnosed between 2008 and 2014 at a large East London hospital. RESULTS: Forty of sixty-one patients were male. Mean age was 34.6 years. 93% of patients were born abroad, mostly from TB-endemic areas (Indian subcontinent: 88%, Africa: 9%). 25% had concomitant pulmonary TB. Median time from symptom onset to ITB diagnosis was 13 weeks (IQR 3-26 weeks). Ten patients were initially treated for IBD, although patients had ITB. The main sites of ITB involvement were the ileocaecum (44%) or small bowel (34%). Five patients had isolated perianal disease. Colonoscopy confirmed a diagnosis of ITB in 77% of those performed. 42 of 61 patients had a diagnosis of ITB confirmed on positive histology and/or microbiology. CONCLUSION: Diagnosis of ITB is often delayed, which may result in significant morbidity. ITB should be excluded in patients with abdominal complaints who come from TB-endemic areas to establish prompt diagnosis and treatment. Diagnosis is challenging but aided by axial imaging, colonoscopy and tissue biopsy for TB culture and histology.

Exploring factors influencing outpatient radiology attendance based on Health Belief Model (HBM): A qualitative study.

INTRODUCTION: Non-attendance for radiology outpatient appointments is a global issue and is associated with adverse clinical outcomes and operational inefficiencies. This paper aims to understand the underlying factors influencing outpatient radiology attendances based on the Health Belief Model (HBM). METHODS: Purposive sampling was used to recruit patients (n=30) for in-depth semi-structured telephone interviews. Inclusion criteria comprised participants who were above 21 years old and fluent in English, while participants reliant on third-party assistance (e.g., nursing homes and prison services), to attend the appointment were excluded. The interviews were recorded and transcribed verbatim. The COREQ (Consolidated Criteria for Reporting Qualitative Research) was utilised to guide the reporting of this study. The data analysis involved a hybrid thematic analysis approach using NVivo. RESULTS: Six key themes associated with appointment adherence in radiology were identified. These themes included: 1) prioritising health and acceptance of current medical conditions; 2) the impact of perceived severity on non-attendance; 3) perceived benefits of attending appointments; 4) perceived barriers to attendance; 5) influential prompts; and 6) confidence in attendance. CONCLUSION: This is the first study of its kind to utilise the HBM to examine factors influencing attendance adherence among radiology outpatients in Singapore. Costs, prompts, and the perceived severity of the condition play pivotal roles in shaping the health-seeking behaviours of these outpatients while professionalism of healthcare staff and barriers to attendance present opportunities for providers to address patients' lack of interest towards their appointments. IMPLICATIONS FOR PRACTICE: Findings of this study will contribute to the development of personalised, targeted interventions for improving patient engagement and attendance in radiology settings.

Acute kidney injury after myeloablative cord blood transplantation in adults: the efficacy of strict monitoring of vancomycin serum trough concentrations.

BACKGROUND: Acute kidney injury (AKI) is a common medical complication after myeloablative allogeneic stem cell transplantation (SCT). We have previously performed a retrospective analysis of AKI after cord blood transplantation (CBT) in adults, and found that the maximum of vancomycin (VCM) trough levels were significantly higher in patients with AKI. Following these results, we have monitored VCM serum trough concentrations more strictly, to not exceed 10.0 mg/L, since 2008. METHODS: In this report, we performed an analysis of AKI in a new group of 38 adult patients with hematological malignancies treated with unrelated CBT after myeloablative conditioning between January 2008 and July 2011. RESULTS: Cumulative incidence of AKI at day 100 after CBT was 34% (95% confidence interval 19-50). The median of the maximum value of VCM trough was 8.8 (4.5-12.2) mg/L. In multivariate analysis, no factor was associated with the incidence of AKI. No transplant-related mortality was observed. The probability of disease-free survival at 2 years was 83%. CONCLUSION: These findings suggest that strict monitoring of VCM serum trough concentrations has a beneficial effect on outcomes of CBT.

Service evaluation of radiographer-led vetting and protocoling of Computed Tomography (CT) scan requests in a Singapore public healthcare institution.

INTRODUCTION: A service improvement project involving the vetting and protocoling of Computed Tomography (CT) scan requests by qualified CT radiographers was initiated in 2018. AIM: This study provides a comprehensive evaluation of how a radiographer-led initiative aims to ensure that the CT scan requests received by the Radiology department are clinically appropriate, which in turn will reduce interruptions to the interpretation and reporting of imaging examinations by radiologists, who might otherwise be required to attend to clinically inappropriate and wrongly protocolled CT scan requests. METHOD: Outpatient CT scan requests received from July to October 2021 were vetted and protocolled by a qualified CT-trained radiographer for parameters which included the appropriateness of the clinical indication, adequacy of patient preparation for the scan, as well as the suitability of the requested examination protocol pertaining to the need for contrast media, multiple contrast-enhanced imaging phases, and the appropriateness of the scan range. RESULTS: Poor patient preparation and insufficient or inaccurate clinical indications were the most common findings during the vetting process (71%). Out of the 64 CT scan requests with protocol errors, 77% were attributed to contrast media type errors. The odds of incorrect CT scan requests increased with the requesting clinician's rank, while there was no such significant correlation with the clinical specialty of the requesting clinician or the CT scan type. CONCLUSION: The meticulous vetting of imaging requests helps to ensure that limited imaging hardware resources are allocated to more clinically appropriate cases, correct protocols are applied to requested imaging scans, and that patients undergoing imaging are adequately prepared, thereby enhancing overall patient care. IMPLICATIONS FOR PRACTICE: Vetting of imaging requests by radiographers, who are capable to make appropriate clinical decisions related to their enhanced level of practice ensures patient safety and optimisation of Radiology resources.

Proteomic data in meningiomas: post-proteomic analysis can reveal novel pathophysiological pathways.

Meningiomas account for approximately 20% of adult primary intracranial tumours. WHO I meningiomas are the most common and are generally benign, but can progress, recur or transform to WHO II or WHO III grades over many years. A systematic review of multiple independent shotgun proteomic analyses of meningioma was performed to provide insight into underlying disease pathways. Shotgun proteomics has been conducted in seven meningioma related studies but there is considerable variation in aims, methodology, statistical power and the use of control tissue between these studies. Fifteen proteins which are different between WHO I and WHO II meningiomas and nine proteins which are different between WHO II and WHO III meningiomas have been described but without a view of their biological significance. Network analysis of proteins different between WHO I and WHO II meningiomas provided a coherent hypothesis for the involvement of these proteins in meningioma. Western blot analyses of meningioma tissue provided a measure of support for a core component in the network (involving VDAC2, APOA1 and HNF4α) but highlighted intrinsic difficulty of proteomic and biochemical analysis of meningiomas (as a consequence of gross alterations in tissue composition). Systematic review of shotgun proteomics and network analysis provides insight into meningioma pathophysiology despite the many barriers and difficulties that are inherent to this type of study.

Comparison between LMA-Classic and AMBU AuraOnce laryngeal mask airway in patients undergoing elective general anaesthesia with positive pressure ventilation.

BACKGROUND: The LMA-Classic laryngeal mask airway (Classic LMA) is an autoclavable and reusable laryngeal mask airway with strong evidence supporting its efficacy and safety. Due to the concern of infection risk particularly of prion disease, various single-use laryngeal mask devices were developed. The Ambu AuraOnce LMA (Ambu LMA) is a single use disposable laryngeal mask airway with special design that conforms better to the anatomy of the airway. OBJECTIVES: The Ambu LMA was compared to the LMA-Classic Classic LMA in respect to ease of insertion, adequacy of seal intraoperatively and postoperative complications in patients undergoing elective general anaesthesia with positive pressure ventilation. METHODS: One hundred and eighteen ASA I and II patients undergoing elective general anaesthesia were randomly allocated into receiving either the Ambu LMA or the Classic LMA. The time taken and number of attempts taken to insert the laryngeal mask was recorded. Intra-operative adequacy of seal was assessed via the amount of nitrous oxide leak using a nitrous oxide analyser. Readings were charted at 0, 20, 40 and 60 minutes of operation. Complications postoperatively (blood stains on the device and occurrence of sore throat) were also recorded. RESULTS: The success of first attempt insertion was comparable between the two groups (Classic LMA 87% versus Ambu LMA 83%). However the time of insertion was significantly shorter in the Ambu LMA group (p = 0.008). Nitrous oxide level was comparable between the two groups up to 20 minutes of operation. At 40 and 60 minutes, the Ambu LMA showed a significant lower nitrous oxide leak compared to the Classic LMA. Postoperatively, incidence of blood stains was comparable between the two groups, however the incidence of sore throat was lower in the Ambu LMA group (p = 0.025). CONCLUSIONS: This study demonstrated that the Ambu LMA was comparable to the Classic LMA in terms of the ease of insertion, but provided better seal during positive pressure ventilation with less postoperative sore throat.

The impact of common variables on non-attendance at a radiology centre in Singapore.

INTRODUCTION: With the increasing demand for medical imaging, non-attendance inhibits private and public radiology practices in Singapore from providing timely care and achieving maximal efficiency. Missed radiological appointments adversely affect clinical and economic outcomes and strain the finite healthcare resources. We examined the prevalence and predictors of patient non-attendance for radiological services at a regional public hospital in Singapore and compared them against other medical imaging centres globally. METHODS: Outpatient records of patients who were scheduled for specialised medical imaging obtained from Radiological Information System (RIS) were retrospectively reviewed. Analysed variables include patient demographics, radiology modalities, visit statuses and appointment lead times where Pearson's chi-square test and Fisher's exact test were used for categorical variables, and independent sample t-test was used for continuous variables. The association between each patient characteristic and non-attendance status was assessed using Binary Logistics Regression. Variables that showed statistical significance in univariate analysis were included in the multivariate logistic regression model to identify the independent risk factors associated with non-attendance. RESULTS: Among the 59,748 outpatient appointments with medical imaging requests, 15.5% did not turn up for their appointments. Logistic regression indicated that patient's age, ethnicity, subsidy status, house ownership, living vicinity to regional hospital cluster, appointment wait times, appointment hours and appointment months were significant factors associated with the failure to attend scheduled radiological examinations. CONCLUSION: Even though predictors of non-attendance remained consistent across medical imaging centres worldwide, Singapore reported a higher prevalence of missed appointments calling for future exploratory studies to understand the population's health-seeking behaviours and ordering patterns of clinicians. IMPLICATIONS FOR PRACTICE: Comparison and identification of these predictors will assist in the design of targeted interventions that may improve patient's adherence and utilisation of imaging services.

The 12-hour shift: radiographers' perspectives and its applicability during a pandemic.

INTRODUCTION: Traditionally, shift work for radiographers at our institution comprised of three shift patterns - morning (8am-2pm), afternoon (2pm-9pm) and night (9pm-8am). However, when COVID-19 was first detected in Singapore in January 2020, the 12-h shift was introduced for better team segregation and deployment to meet the service needs of the Emergency Department. The 12-h shift consisted of the day (9am-9pm) and night (9pm-9am) shifts. While the 12-h shift is common to nursing practices, it is new to the radiography profession within the study centre. This study explores the radiographers' perspectives of the new shift and the impact of shift patterns on radiographers' wellness and work performance compared to the original three shift patterns. METHODS: A mixed-methods design study was adopted for this single-centre evaluation. An anonymous online questionnaire was administered to radiographers who had experienced both shift types. Additionally, the number of radiographers who had taken sick leave, and images rejected and accepted from the X-ray consoles were retrospectively collected to measure the impact of the new shift. RESULTS: Radiographers experienced fatigue and appreciated the longer rest days associated with the 12-h shift. Additionally, the sick leave rates and image reject counts were more favourable with the 12-h shift pattern. CONCLUSION: The findings indicate that the extended shift hours are effective during a pandemic but may result in radiographer burnout during a prolonged outbreak. IMPLICATIONS FOR PRACTICE: Studying these variables will provide an effective starting point in understanding the efficacy and applicability of a 12-h shift system during pandemic periods.

TLR9 and TLR4 are required for the development of autoimmunity and lupus nephritis in pristane nephropathy.

Systemic lupus erythematosus is a common autoimmune disease, with kidney involvement a serious complication associated with poor prognosis. Humoral immune responses constitute the hallmark of disease, however T helper cells are required for the generation of autoantibodies, as well as the induction and progression of renal injury. Administration of pristane to genetically intact mice results in the development of hypergammaglobulinaemia with the production of lupus like autoantibodies and proliferative glomerulonephritis, with similarities to human lupus nephritis. TLRs are intricately linked to the development of autoimmunity and are involved in the development of lupus nephritis. We injected wild type, TLR9-/- and TLR4-/- mice with pristane and assessed cellular and humoral autoimmunity and renal injury, 8 months later. TLR9-/- mice demonstrated a predominant decrease in Th1 cytokine production which resulted in decreased anti-RNP antibody levels, while anti-dsDNA levels remained intact. Compared to wild type mice treated with pristane, functional and histological renal injury and glomerular immunoglobulin and complement deposition was decreased in TLR9-/- mice. TLR4-/- mice demonstrated a global decrease in both Th1, IFNγ, and Th17 associated IL-17A and IL-6 cytokine production. Autoantibody levels of anti-dsDNA and anti-RNP were both decreased. Renal injury was attenuated in TLR4-/- mice which demonstrated less glomerular immunoglobulin and complement deposition. These results demonstrate that both TLR9 and TLR4 are required for 'full-blown' autoimmunity and organ injury in experimental lupus induced by pristane.

A novel molecule, SLURP-1, enhances the survival of periodontal ligament fibroblasts.

BACKGROUND AND OBJECTIVE: The mechanism behind the survival of periodontal ligament fibroblasts is critical for the maintenance of periodontal ligament tissue. However, the number of known proteins that are involved in this action is limited. The aim of this study was to examine the role of a novel molecule, secreted mammalian Ly-6/urokinase-type plasminogen activator receptor-related protein 1 (SLURP-1), in periodontal ligament fibroblast survival. MATERIAL AND METHODS: Human periodontal ligament fibroblasts were isolated from eight healthy human donors using established protocols. Gene expression for SLURP-1 was analysed using the reverse transcriptase-polymerase chain reaction, while protein expression was examined by immunoblotting with a SLURP-1 antibody. In addition, the apoptotic effect was examined using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay. RESULTS: Messenger RNA for SLURP-1 was expressed in the periodontal ligament, gingival fibroblasts, oral keratinocytes and bone. Moreover, the protein was secreted by both periodontal ligament and gingival fibroblasts. Functional analysis revealed that SLURP-1 substantially enhanced cell survival in periodontal ligament fibroblasts by the anti-apoptotic signal phosphatidylinositol 3-kinase. CONCLUSION: These findings suggest that SLURP-1 may play an important role in the control and maintenance of the periodontal ligament by protecting the periodontal ligament fibroblasts from apoptosis.

Cardiovascular toxicity of cryopreserved cord blood cell infusion.

Although infusion of cryopreserved bone marrow or peripheral blood stem cell is associated with a variety of symptoms, there have been no reports detailing the data of infusion-related toxicities of cryopreserved cord blood (CB) units. We prospectively evaluated the incidence and significance of infusion-related toxicities in 34 adult patients undergoing unrelated CB transplantation. Cryopreserved CB units were thawed and immediately infused, unfiltered, through a central intravenous catheter without further manipulation. Heart rate, blood pressure, oxygen saturation and clinical symptoms were recorded during and after infusion. Twenty-four percent of patients experienced non-cardiovascular toxicities related to infusion. The incidence of systolic and diastolic hypertension and bradycardia was 58, 64 and 32%, respectively. Although three patients (9%) with severe systolic hypertension after the infusion required treatment with antihypertensive agents, no patients experienced life-threatening side effects or needed discontinuation of CB unit infusion. Patient or transplant characteristics had no effect on the hypertension and bradycardia related to the infusion of CB. These data suggest that infusion of cryopreserved CB without further manipulation after thawing is safe and well tolerated. However, cardiovascular toxicities including hypertension and bradycardia were frequently observed.

Preemptive therapy with ganciclovir 5 mg/kg once daily for cytomegalovirus infection after unrelated cord blood transplantation.

The efficacy and safety of preemptive therapy using ganciclovir (GCV) 5 mg/kg once daily for CMV infection after unrelated cord blood transplantation (CBT) were studied. The initial preemptive therapy with GCV 5 mg/kg once daily led to resolution of CMV antigenemia in 25 of 34 patients (74%). In the remaining 9 patients (26%), antigenemia resolved after dose-escalation of GCV or change to foscarnet therapy. Recurrence of antigenemia was seen in 18 patients (53%). A total of 12 patients received the second preemptive therapy with GCV 5 mg/kg once daily, which led to resolution of antigenemia in 11 of 12 patients (92%). The remaining 1 patient (8%) required change to foscarnet therapy. None of 34 patients developed CMV disease. Neutropenia with an absolute neutrophil number of less than 1 and 0.5 x 10(9) per liter after GCV therapy occurred in 12 (35%) and 1 (3%) patients, respectively, after the initial therapy, and in 2 (17%) and 0 (0%) patients, respectively, after the second therapy. No patients developed neutropenic fever or secondary graft failure after GCV therapy. There were no deaths directly attributable to GCV therapy. The present study suggests that antigenemia-based preemptive strategy using GCV 5 mg/kg once daily is feasible and effective for CBT recipients.

No occurrence of Pneumocystis jiroveci (carinii) pneumonia in 120 adults undergoing myeloablative unrelated cord blood transplantation.

The incidence of pneumonia caused by Pneumocystis carinii (PCP) (organism now renamed Pneumocystis jiroveci) during the early period after cord blood transplantation (CBT) was studied in 120 adults. Initially 89 patients (74%) received oral administration of 2 single-strength trimethoprim-sulfamethoxazole (TMP-SMZ) tablets twice daily from day -21. In 45 of 89 patients (51%), TMP-SMZ administration for a scheduled duration was completed. In the remaining 44 patients (49%), however, TMP-SMZ administration was discontinued prior to day -3 because of toxicity. Among these patients, 42 subsequently received aerosolized pentamidine (AP) on a median of day -13 (range, -20 to -6). Thirty-one patients (26%) received AP without TMP-SMZ administration on a median of day -14 (range, -21 to -9). None of the 120 patients were diagnosed with PCP within 100 days or 2 years after CBT; however, one patient who received AP before CBT but no prophylaxis after CBT developed cerebral toxoplasmosis on day +91. Pre-transplant prophylaxis against PCP did not significantly affect transplantation-related mortality or disease-free survival at 2 years after CBT. The results suggest that PCP during the early period after CBT can be effectively prevented by any pre-transplant prophylactic method.

The adapter protein Grb10 associates preferentially with the insulin receptor as compared with the IGF-I receptor in mouse fibroblasts.

To identify receptor-associated proteins that may contribute to the specificity of insulin and IGF-I signaling responses, a mouse embryo library was screened using the yeast two-hybrid system. Multiple receptor-interactive clones encoding the SH2 domain of the adapter protein Grb10 were isolated. Subsequent cloning of the full-length Grb10 sequence from a mouse fat cDNA library defined a previously unknown Grb10 variant, that appears to be the predominant isoform in mouse tissues. Receptor-deficient R- cells (fibroblasts from mice with homologous disruption of the IGF-I receptor gene) and transfected R- cells expressing either insulin receptors (R-IR cells) or IGF-I receptors (R+ cells) were used to investigate the specificity of Grb10 interaction with the two related receptors. Hormone-activated insulin receptors in R-IR cells coprecipitated with three species, all recognized as Grb10 isoforms by specific Grb10 antibody. Under the same conditions, Grb10 was essentially undetectable in IGF-I receptor immunoprecipitates from stimulated R+ cells. Grb10 association with insulin receptors was maximal at 10 nM insulin stimulation and sustained from 5-10 min after hormone stimulation in R-IR cells. In conclusion, Grb10 interacts preferentially with insulin vs. IGF-I receptors in intact cells and, thus, may have a role in mediating insulin receptor-specific cellular responses.