The Different MRI Features of Hepatocellular Adenoma and Hepatocellular Carcinoma.

Background: Hepatocellular adenomas (HCAs) are benign tumours that may be broken down into three different molecular pathogenic categories: catenin activator, hepatic cell nuclear agent 1 (HNF- 1) that has been inactivated, and Inflammatory hepatic adenomas are a genetic and pathological subtype of hepatic adenoma. Methodology: An analysis of 50 HCA cases was conducted to identify the magnetic resonance imaging characteristics that were specifically related to each HCA subtype IV. This method included 50 patients in total for the study, with 30 of them being new cases. Four cases involving medicine, pathology, surgery, and radiology were gathered and examined. Results: As per these analyses for inactivated HNF-1, the sure predictive esteem about homogeneous indicator spillage on the compound shift pictures could have been as high as 100%, negative predictive quality could have been as high as 94.7%, affectability could have been as high as 86.7%, and specificity could have been as high as 100%. Enhancement of the solid blood vessels to support the ongoing and future stages of the portal vein change. It took a certain predictive quality of 88.5%, a negative predictive worth of about 84%, an affectability of about 85.2%, and more specificity of about 87.5% to diagnose incendiary HCA from the predominant signs seen for T2W successions linked with late constant upgrades. Conclusions: Both HNF-1-mutated HCAs and incendiary HCAs need to be associated with specific magnetic resonance imaging phenotypes characterized independently as having diffused lipid repartition and sinusoidal expansion.

Pneumorrhachis Following Neck Penetrating Injury: A Case Report.

The development of air in the spinal canal is an uncommon and usually asymptomatic event. Also known as pneumorrhachis (PNR), the main information about this phenomenon is based on a few case reports published previously. It is highly difficult to identify this entity clinically, and in most publications, PNR was incidentally identified during image procedures, mainly computed tomography (CT) scans. With the advancement of technology and the development of guidelines for the treatment of penetrating and neck injuries, the number of PNR diagnosis has increased. It is also a common agreement among the articles reviewed that the least common cause of PNR is traumatic events. This report presents a rare case of pneumorrhachis as a consequence of a penetrating neck injury. The studied patient was a 27-year-old female with multiple stab wounds on the left posterior side of the neck and left shoulder, thereby developing left-side body weakness as a consequence of the wound. The patient was immediately evaluated and managed by the emergency team, and as the patient was vitally stable, she was shifted to an urgent CT scan. CT scan showed subarachnoid air focus, multiple extradural air foci, and spinal cord injury on the cervical spine. This patient was treated conservatively, but her neurological symptoms persisted until discharge.

Comparison of Three Circular Frames in Lower Limb Deformity Correction: A Biomechanical Study.

Background The use of circular frames in correcting lower limb deformity is well-established and has evolved dramatically over the years. Three new frames have been introduced recently, and this study is set to compare them in terms of accuracy and efficiency in correcting a similar long bone deformity. These frames are the Taylor Spatial Frame (TSF; Smith & Nephew, London, United Kingdom), the Truelok Hexapod System (TL-HEX; Orthofix, Lewisville, Texas), and Orthex (OrthoPediatrics, Warsaw, Indiana). Methods This is a biomechanical study comparing the above three types of circular frames to correct similar deformities in Sawbones models. The deformities that are compared were: (1) 30° valgus deformity of the distal femur; (2) 30° varus deformity of the proximal tibia. Each frame was applied to the deformed bone in the standard way that we apply to normal bone. X-rays were taken before and after the deformity correction. The frames' software was used to estimate the deformities. The variations between the software's estimations and the known bone deformities were compared. Residual deformity after initial correction and the number of re-programmings was compared among these three frames. The least residual deformity and re-programming is the favorable outcome. Results All the Sawbones models had a 30° actual coronal angulation. The Orthex software estimated the deformity at around 25.35° (SD 4.6), TSF 25.6° (SD 2), and TL-HEX 29.87° (SD 2.1). One-way analysis of variance (ANOVA) showed a significant difference in the findings (P-value 0.014). Accuracy was measured by comparing the residual deformity in angulation in the coronal plane after the first and second correction. The Orthex median residual deformity was 1°, TSF was 2.5°, and TL-HEX was 3° with a range of less than 5° for all of them. The independent samples Kruskal-Wallis test shows that there is no significant difference between the three groups (P=0.549). The frequency of strut changes required throughout the correction was not significant among the three frames using the Fisher exact test (P=0.336). TSF struts are not designed to be readjusted. Conclusion The three frames were comparable in terms of accurate correction of the two deformities, strut changes, and strut adjustments. The TL-HEX frame software was superior to other frames in terms of analyzing the deformity but the difference, although statistically significant clinically, was not.

Effects of healthy psychological course.

The aim of this research is to prepare a healthy psychological course and study its impact on the levels of serum uric acid (SUA) and pessimism and depression. The research sample was limited to teaching staff of the Iraqi State Universities in Baghdad, who were retired at 63-65 years of age. Data were collected by independent group experimental approach via pre- and posttest measurements. The study sample consisted of 21 people with cases of pessimism and depression. The sample was randomly chosen based on their consent to do pre- and posttests and to be subjected to healthy psychological approach. After collecting the data obtained from the samples and processing them statistically, the results showed that the healthy psychological course had a positive effect on the levels of SUA, pessimism, and depression of the research sample.

Effects of Obesity on the pulmonary function test

Aim: To evaluate the effects of increasing BMI on the Respiratory function. Introduction: There is a worldwide increasing prevalence of overweihgt and obesity. Researchers have found that obesity affects the respiratory function leading to different respiratory medical illnesses, including asthma and obstructive deep apnea. The effect of obesity on the pulmonary functiion is assisted using different anthropometric measurements, like BMI, waist circumference, skin fold, etc. So the aim of this study is to evaluate the effect of increasing BMI on different respiratory function test measures. Methods: 23 adult males with BMI of 25 and above were included in the study and compared with 18 normal weight adult males with BMI of (18-24.99) regarding different measures of PFT like: FVC, FEV1, PEFR and FEF. Results: no significant difference was found between the two groupsñ. Conclusions: there were no effects of increasing BMI on the respiratory functions

Direct head injury caused by a tear gas cartridge. Questions on safety: A case report from Iraq and review of the literature.

INTRODUCTION AND BACKGROUND: Primary injuries from tear gas weapons include injuries to the visual and respiratory systems and skin. However, few studies have reported direct mechanical brain injuries from tear gas weapons. CASE REPORT: A 27-year-old male presented to the emergency department of a neurosurgery teaching hospital in Baghdad, Iraq, with a penetrating head injury of unknown source. DISCUSSION: Tear gas weapons are considered safe, but tear gas exposure causes severe complications. Traumatic brain injuries as a direct effect of tear gas bombs are rarely reported in the literature. Tear gas cartridge injuries should be managed in the same manner as any penetrating brain injury, with appropriate neuromonitoring. This monitoring is crucial for the detection and prevention of secondary brain insults. CONCLUSION: Emergency medicine specialists and neurosurgeons should be aware that tear gas weapons are not always safe, and they should anticipate chemical, thermal and mechanical side effects of tear gas weapons. The literature and our results suggest that these weapons should not be considered civil and harmless.

The E-wave propagation index (EPI): A novel echocardiographic parameter for prediction of left ventricular thrombus. Derivation from computational fluid dynamic modeling and validation on human subjects.

BACKGROUND: To describe the derivation and validation of a novel echocardiographic metric for prediction of left ventricle thrombus (LVT). METHODS: Computational fluid dynamic modeling using cardiac CT images was used to derive a novel echocardiography-based metric to predict the presence of LVT. We retrospectively reviewed 25 transthoracic echocardiograms showing definite LVT (LVT group). We then randomly selected 25 patients with LVEF ≥55% (Normal EF group) and 25 patients with severe cardiomyopathy (CMP) with LVEF ≤40% without evidence of LVT (CMP group). The E-wave Propagation Index (EPI) was measured as the E-wave velocity time-integral divided by the LV length. An EPI>1 indicates penetration of the mitral jet into the apex whereas an EPI<1 is indicative of incomplete apical washout. The mean EPI was compared between the three groups. Crude and adjusted odd ratios of EPI and LVT association were also measured. RESULTS: Mean EPI was highest for the normal EF group and lowest in the LVT group (1.7 vs. 0.8; p<0.0001). Mean EPI also differed significantly between LVT and CMP groups (0.8 vs. 1.2; p<0.0001). 88% of the LVT group had EPI <1.0 compared to only 20% of the CMP group (p<0.0001). Among the LVT and CMP groups, an EPI <1 increased the odd ratio of LVT by 53.7 times (95% CI: 6.9-416) controlling for LVEF and LV volume. CONCLUSIONS: The E-wave propagation index is a novel, easily-obtainable, echocardiographic metric to evaluate apical LV flow. An EPI of less than 1 is an independent predictor of LVT formation.

Association of global DNA hypomethylation with clinicopathological variables in colonic tumors of Iraqi patients.

BACKGROUND/AIM: Colorectal cancer (CRC) ranks sixth among the most common 10 cancers in Iraq. It is a foremost public health dilemma and there is improved interest in understanding the fundamental principles of its molecular biology. DNA methylation in cancer has become the issue of passionate investigation. As compared with normal cells, the malignant cells show major disruptions in their DNA methylation patterns. We aimed to assess the association of global DNA hypomethylation in colonic adenomas and carcinomas of Iraqi patients, measured by immunohistochemistry of 5-methylcytosin, with different clinicopathological variables. PATIENTS AND METHODS: Thirty tissue paraffin blocks from patients with colorectal adenomas, 30 tissue paraffin blocks from patients with colorectal adenocarcinomas, and 30 samples of apparently normal colonic tissue taken from autopsy cases as a control group were included in the present study. From each block, two sections of 5 µm thickness were taken, one section was stained with Hematoxylin and Eosin for revision of histopathological diagnosis and one section was immunohistochemically stained for 5-methylcytosine (5mC) and digitally analyzed by AperioImageScope software. RESULTS: The mean digital value of 5mC immunohistochemical expression was sequentially decreased during neoplastic progression from normal colonic tissue into adenoma and then to carcinoma. The mean digital value of 5mC expression was significantly lower in large size adenomas (≥1 cm), and those with severe dysplasia. Concerning carcinoma cases, 5mC expression was significantly lower in stage C2. CONCLUSIONS: The immunohistochemical evaluation of 5mC yields refined information on colorectal tumor biology in adenoma and carcinoma. Global DNA hypomethylation reflected by low immunohistochemical expression of 5-mC is associated with advanced colorectal adenomatous polyps suggesting that it is an early event in colorectal carcinogenesis. Also this hypomethylation can reflect bad prognosis of patients with colorectal cancer by its correlation to higher tumor stage.

Effect of intravenous infusion of iodinated contrast media on the coronary blood flow in dogs.

BACKGROUND: Coronary computed tomography angiography (CCTA) is obtained using peripheral intravenous iodinated contrast agents (ICA) injection. There is continuing attempts to derive coronary physiological information like coronary blood flow (CBF) and/or fractional flow reserve from CCTA images. However, no data is available regarding the effect of peripheral intravenous injection of ICA on CBF. METHODS: A series of 4 experiments was performed using healthy mongrel dogs. All dogs underwent anesthesia and open thoracotomy with placement of ultrasound flowmeter to one of the coronary artery to provide real time absolute CBF measurements. Different infusion protocols of Isovue-370 and Visipaque-320 were injected into a peripheral vein. Similar doses of normal saline injection were performed to be used as controls. The effect of iodinated contrast media injection on absolute coronary blood flow was monitored and recorded. RESULTS: Injection of normal saline in the peripheral vein did not produce any significant increase in CBF. Peripheral intravenous injection of ICA resulted in a consistent increase of 40-73% in absolute CBF as recorded 5 minutes post-contrast administration. The contrast effect starts about 30 seconds and peaks at about 2 minutepost-contrast injection then slowly fades away in the following 10-15 min. The increase in the CBF was dose related. There was greater increase in the CBF to 50 ml infusion compared to 25 ml infusion of both Visipaque and Isovue. CONCLUSIONS: Peripheral venous administration of iodinated contrast-media in dogs results in a dose related, significant and prolonged increase in CBF.

Paan without tobacco: an independent risk factor for oral cancer.

Oral cancer is the second most common cancer in women and the third most common in men in Pakistan. Tobacco is smoked and chewed extensively in Pakistan. Paan is a quid of piper betel leaf that contains areca nut, lime, condiment, sweeteners, and sometimes tobacco, which is also used extensively. We did this study to clarify the independent association of paan and oral cancer. Between July 1996 and March 1998, we recruited biopsy-proven, primary cases of oral squamous-cell carcinoma, from 3 tertiary teaching centers in Karachi, Pakistan, and controls pair-matched for age, gender, hospital and time of occurrence, excluding persons with a past or present history of any malignancy. There were 79 cases and 149 controls. Approximately 68% of the cases were men, 49 years old on average, the youngest being 22 years old and the eldest 80. People with oral submucous fibrosis were 19.1 times more likely to develop oral cancer than those without it, after adjusting for other risk factors. People using paan without tobacco were 9.9 times, those using paan with tobacco 8.4 times, more likely to develop oral cancer as compared with non-users, after adjustment for other covariates. This study identifies an independent effect of paan without tobacco in the causation of oral cancer. Its findings may be of significance in South Asian communities where paan is used, and among health-care providers who treat persons from South Asia.

National reevaluation of staging in Wilms tumor.

In order to evaluate if incorrect staging of Wilms tumor resulted in inadequate treatment a retrospective reevaluation was performed. During 1982-1990 153 patients were treated in Sweden. The review revealed that 6 cases were not Wilms tumor and 25 cases had incomplete information. The remaining material consisted of 122 cases. The survey of the charges revealed that the initial distribution was stage I 58, stage II 17, stage III 21, stage IV 15 and stage V 11. The stage was changed in 12 cases, mainly in the initial stage I. The causes for changing of the stage were thick needle puncture preoperatively in 4, capsule histologically not intact 4, tumor not radically excised 2, tumor rupture peroperatively 1 and lymph node malignancy 1. The staging procedure cannot be safely performed by a single doctor. It is dependent on cooperation in a pediatric oncologic team including the pediatric surgeon.

Plasma and urine levels of methotrexate and 7-hydroxymethotrexate in children with ALL during maintenance therapy with weekly oral methotrexate.

A new high-performance liquid chromatographic assay was used to determine methotrexate (MTX) and its main metabolite, 7-hydroxymethotrexate (7-OH-MTX), in the plasma (n = 17) and urine (n = 14) of children (age 3-12 years) on maintenance therapy for acute lymphocytic leukemia (n = 14) or non-Hodgkin's lymphoma (n = 3). Each child received oral doses of weekly MTX (4.0-29 mg/m2) and daily 6-mercaptopurine (40-111 mg/m2). Plasma samples were collected daily from two children during the 1-week dose interval. A limited sampling strategy was designed, whereby 2 days of blood sampling were used in the other 15 patients. Morning urine samples were collected daily for 1 week following MTX intake from 14 of the children. MTX was detectable in all plasma and urine samples for the entire dose interval. The main metabolite, 7-OH-MTX, could be detected in plasma and urine from all patients on the first day after dose intake but only in a few patients during the whole dose interval. Interpatient variability of MTX and 7-OH-MTX levels was high at all points during the week. Significant correlation were found between the urinary MTX levels on days 2 and 7 and plasma MTX levels on day 2 after intake. No significant correlation was found between drug levels in plasma or urine and liver function tests in the children showing signs of mild liver injury. This assay provides a tool for further studies on the role of pharmacokinetics for the clinical effects of weekly oral low-dose MTX given alone or in combination with 6-mercaptopurine.

Relapse factors during maintenance therapy of acute lymphoblastic leukemia in children.

A statistical analysis of possible risk factors for relapse during maintenance therapy (MT) for acute lymphoblastic leukemia (ALL) has been performed. The patient material consists of 64 patients. Twenty-six patients were classified as standard risk (SR), 21 as intermediate risk (IR), and 17 as high-risk (HR) patients. Seventeen patients relapsed and 50 patients (78%) are alive at a median observation period of 86 months (range 39-146 months). Mean white blood cell count (mean WBC) based on weekly determinations, duration of treatment interruption, and the number of infectious episodes were calculated in each patient during the first 6 months of MT. In analyses starting at 6 months after the beginning of MT, these factors were related to relapse risk, time to relapse, and time to infection. Using the median WBC value (3.9 x 10(9)/L) of all patients during the first 6 months as a cutoff point, 14 patients with levels higher, and 3 patients with levels lower relapsed (p = .0004). Adjustment of mean WBC for leukemia risk groups had no influence on the analysis. Time to relapse was related to duration of interruption of MT (p less than .01). Time to relapse was not related to leukemia risk groups. Infection frequency was higher in HR patients compared to SR and IR risk patients (p = .04). As WBC level had a prognostic value and was previously shown to be related to 6-mercaptopurine (6-MP) peak plasma concentration, monitoring 6-MP plasma levels during MT could be helpful for optimizing treatment.

Intraindividual variation in 6-mercaptopurine pharmacokinetics during oral maintenance therapy of children with acute lymphoblastic leukaemia.

Intraindividual variation in 6-mercaptopurine (6-MP) kinetics has been little studied. It has now been examined in 18 children with acute lymphoblastic leukaemia (ALL). On 2 to 4 occasions in each patient drug concentrations in plasma and red cells were followed for 4 h after administration by means of HPLC. The mean individual coefficient of variation (C.V.) in AUC was 57.9% and it was not related to dose or concentration. The variation was the same in plasma and in red cells. It is concluded that regular monitoring of 6-mercaptopurine concentration would identify periods when a patient deviates strongly from the mean range. Both undertreatment and concentration-dependent toxicity could then be corrected.

The course of biological parameters and 6-mercaptopurine pharmacokinetics during maintenance treatment of children with acute lymphoblastic leukaemia.

Twenty patients on maintenance therapy (MT) for acute lymphoblastic leukaemia (ALL) with oral 6-mercaptopurine (6-MP) and methotrexate (MTX) were studied. White cell and red cell indices and platelets counts were monitored every second week as were drug levels. Mean values for 6-MP and MTX doses, and blood component parameters were calculated for each 6-month period for the whole patient group. 6-MP plasma concentrations and liver-function tests were determined once every six months and mean values calculated. 6-MP and MTX mean doses did not change significantly during MT. The mean area under the concentration versus time curve (AUC) 0-4 hours varied slightly from the start to the end of the MT (257 and 296 ng/ml.h, respectively). The mean plasma peak concentration increased from 98 ng/ml to 195 ng/ml (p less than 0.01) during the same period. There were significant decreases between the initial white blood cell counts (WBC) and red blood cell counts (RBC) as compared to levels at the end of therapy (p less than 0.01 and 0.02, respectively). A linear correlation was found between 6-MP peak concentrations and both WBC (r = 0.96) and RBC (r = 0.87). At the end of MT liver function tests became normal in all except 6 patients. In conclusion, MT have moderate effects on bone marrow and liver and monitoring 6-MP plasma concentration might be of value for determination of the optimal WBC levels during MT.

6-mercaptopurine plasma levels in children with acute lymphoblastic leukemia: relation to relapse risk and myelotoxicity.

Plasma levels of 6-mercaptopurine were determined in 22 consecutive children with acute lymphoblastic leukemia on oral remission maintenance therapy during the time period of August 1984 to January 1988. Each child received the drug once daily for up to 3 years and was studied repeatedly (1-12 times). An HPLC method was used for drug analysis. We found large interpatient variations in the mean peak plasma concentration (range of 50-424 ng/ml) and in the mean area under the concentration vs. time from 0-4 h curve (range of 82-637 ng ml-1 h). There were also pronounced variations between different sampling occasions in the same patient. Nine of the 22 patients had complications during the maintenance therapy. Five children with a mean peak plasma level below 135 ng/ml and a mean area under the curve (AUC) value below 251 ng ml-1 h relapsed (three in the central nervous system and two in the bone marrow). Both children with a bone marrow relapse died. Relapse risk was related to the AUC (p less than 0.05). Four children with a mean peak plasma level above 166 ng/ml and a mean AUC value above 363 ng/ml/h developed severe myelotoxicity, which necessitated a temporary cessation of the maintenance therapy. In addition, two patient relapsed 6 and 11 months after termination of maintenance therapy. Their mean peak and AUC values were not low but the concentrations decreased markedly towards the end of the maintenance period. The results indicate that the plasma levels of 6-mercaptopurine, when determined repeatedly, might be of significance for the outcome of the remission maintenance treatment.

Variability of 6-mercaptopurine pharmacokinetics during oral maintenance therapy of children with acute leukemia.

The effects of some environmental and genetic factors on the inter- and intraindividual variations of 6-mercaptopurine (6-MP) pharmacokinetics were studied in children on oral remission maintenance therapy for acute lymphoblastic leukemia or non-Hodgkin's lymphoma. Blood samples were obtained 0-4 h after drug intake. 6-MP concentrations were determined in plasma and in erythrocyte concentrates. The influence of food on the pharmacokinetics was examined in a prospective study of 15 children. Each child was examined four times, twice in the fasted state and twice after intake of a standardized, milky, breakfast. There were pronounced inter- and intraindividual variations. Food intake seemed to reduce these variations but there were no significant changes in peak concentrations and area under the plasma concentration vs time curves (AUC) between the fasted and fed states. Food intake reduced the time to peak concentration both in plasma, from 1.8 h to 1.1 h (P less than 0.01) and in red blood cells, from 1.8 h to 1.3 h (P less than 0.01). Retrospective subdivision of the patients indicated a tendency for different pharmacokinetic patterns according to dose; five out of seven patients receiving greater than 70 mg m-2 had a higher AUC in the fasting state, while five out of eight patients receiving less than 70 mg m-2 had a higher AUC in the fed state. The cytochrome P-450-dependent hydroxylation capacity was evaluated with debrisoquine but no correlation was found to the pharmacokinetics of 6-MP.

Fine needle aspiration cytology (FNAC) of the testes in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma: preliminary report.

Eighteen patients with childhood acute lymphoblastic (ALL) or non-Hodgkin's lymphoma (NHL) in remission and 2 patients with ALL in suspected testicular relapses were studied by testicular fine needle aspiration cytology (FNAC). Well-preserved testicular cells, both singly and in small clusters, were considered indicative of an adequate aspiration. Of 18 patients in remission, 17 had at least one adequate sample from each testis and one showed evidence of leukemic infiltrate. None of these patients experienced a relapse during a median follow up of 4 years. In 2 other patients with clinically suspected testicular relapses, the smears from fine needle aspirates contained numerous malignant lymphoid cells that could be readily distinguished from seminiferous tubular cells. The observations indicate that FNAC is a promising new approach to study testicular conditions in childhood ALL and NHL. A larger prospective study and accumulation of additional follow-up data is required before a definitive evaluation of the technique can be made.

6-Mercaptopurine in cerebrospinal fluid during oral maintenance therapy of children with acute lymphoblastic leukemia.

In three children receiving oral remission maintenance therapy for acute lymphoblastic leukemia, the concentrations of 6-mercaptopurine (6-MP) in cerebrospinal fluid (CSF), plasma and red blood cells were compared. CSF samples were obtained from an Ommaya reservoir previously inserted for treatment of CNS relapse. At the time of the study, the children were all in remission and had been on oral 6-MP (42-63 mg m-2) once daily for at least 24 weeks. Immediately before dose intake on the day of study (about 24 h after last dose), the concentrations of 6-MP in CSF, plasma and red blood cells were rather similar and below 20 ng ml-1 in all patients. After dose intake, the concentrations in plasma and in red blood cells increased to 40-200 ng nl-1 within 0.5-4 h. In contrast, the concentration of 6-MP in the CSF remained fairly constant around 4-10 ng ml-1 throughout the time period studied (up to 4 h). It is concluded that 6-MP can be detected in CSF during oral maintenance therapy and that the drug has different pharmacokinetic profile in CSF to that in plasma and red blood cells. Further studies are necessary to evaluate the significance of the 6-MP concentrations obtained in CSF for the prevention of CNS relapse.

Large interindividual variations in the pharmacokinetics of oral 6-mercaptopurine in maintenance therapy of children with acute leukaemia and non-Hodgkin lymphoma.

The concentrations of 6-mercaptopurine were studied in plasma and red blood cells from 10 children with acute leukaemia or non-Hodgkin lymphoma receiving oral maintenance therapy. The doses varied between 25 and 79 mg/m2 body surface once daily. Large interindividual differences were found in the concentrations both in plasma and in red blood cells. There was no clear relationship between the dose administered and the concentrations obtained. However, in each patient the concentrations in plasma and in red blood cells were very similar. In most patients, the peak concentrations were reached 1-2 hours after dose intake and the concentrations then declined with half-lives less than 1 hour. Further studies are necessary to evaluate the potential value of drug level monitoring in optimizing treatment with oral 6-mercaptopurine.