Tom 8 (2014): Zeszyt 4 (August 2014)

Background: Chronic hepatitis C is a common cause of advanced liver disease and appropriate treatment has been complex and a challenge. Reaction of individual genotypes to classical pegylated interferon-ribavirin therapy differs and no success has been achieved in some even after repeated therapy cycles. New types of so called directly acting antivirals (DAAs) are hopeful, as shown in many recent clinical studies, and triple therapy regimens involving DAA are becoming the new standard of care.

Objective: To summarize knowledge about the relationship between HCV therapeutic regimens and the genetic background of the host represented by interleukin 28B (IL28B) gene polymorphisms. In the first part, the host basic mechanisms in specific and innate immunity are introduced. The IL28B genotype and its role in the course of HCV treatment are described in the second part.

Methods: We searched and summarized publications on HCV therapeutic regimens and host IL28B polymorphisms.

Results: Compared to classical regimens, the association between IL28B polymorphism and treatment outcome of HCV infected patients is weaker in triple therapy using first generation DAAs boceprevir and telaprevir.

Conclusions: The association between IL28B polymorphism and treatment outcome is lessened with availability of new therapeutic regimens. Nevertheless, IL28B genotyping may still be useful for individualization of treatment strategies.

Background: Chinese university freshmen receive 4-weeks military training that involved moderate to intense physical exercise. Studies have demonstrated heterogeneous effects of exercise on the autonomic nervous system.

Objective: To evaluate the effects of training on the autonomic nervous system noninvasively using electrogastrograms, heart rate variability (HRV), pulse rate, and the sympathetic skin response (SSR).

Methods: Twenty freshmen received all assessments in the fasting state and after a standard meal: (1) one week before the training, (2) at the end of the second week of the training, and (3) one week after the training.

Results: (1) The training had a significant effect on meal-induced gastric pacemaker activity. Before the training, a standard meal did not increase the dominant frequency of gastric slow waves, but the frequency increased during and after the training; (2) The preprandial high frequency (HF), low frequency (LF), and very low frequency (VLF) components of heart rate variability decreased significantly after the training. The ratio of the LF and HF (LF/HF) of the heart rate variability (HRV) did not significantly change after a meal or training condition. The basal pulse rate did not change. The latencies of the sympathetic skin response (SSR), as measured in the arm muscle, increased in response to the training.

Conclusion: Military training affects meal-induced changes in gastric pacemaker activity, causes a marked reduction of the vagal tone to the heart with maintenance of the vagal-sympathetic balance, and its effects on SSR may reflect a reduction in sympathetic tone.

Background: To date, blood and urine analyses have been the major methods of detecting methamphetamine (MA) use in Thailand. Recently, hair analysis has been introduced as an alternative and complementary procedure.

Objectives: To validate a simple, rapid, and economical method of analyzing hair for MA and its metabolite, amphetamine (AM).

Methods: The analysis employed solid-phase microextraction (SPME) coupled with gas chromatography and mass spectrometry (GC-MS). Simplicity, rapidity, and economy were achieved, in part, by optimizing SPME conditions and by eliminating deuterated reagents and the derivatization step in GC-MS. The validated method was employed to detect and quantify MA in 1,111 hair samples of young Thai research volunteers who reported using MA in the form of so-called “yaba” tablets at least 3 times during the previous 3 months.

Results: Validated data from the study indicated that the method’s linearity, accuracy, precision, limit of detection (LOD) and limit of quantitation (LOQ) met international standards for hair analysis of MA. Expressed as ng of MA per mg of hair (ng/mg), the LOQ was 0.5 ng/mg (102.39% accuracy, 5.46% precision). The method was less sensitive for quantification of AM in hair, with a LOQ of 2.5 ng/mg (103.41% accuracy, 6.95% precision). Using 0.5 ng/mg as a cutoff in the analysis of samples provided by admitted MA users, the study yielded an overall detection rate for MA of 35.5%, with a range of 0.51-54.61 ng/mg; the mean MA level was 4.90 ± 6.78 (±SD) ng/mg. Thirty-one percent of the participants reported they had consumed fewer than 10 yaba tablets during the previous 3 months. Of this group, 29% had hair samples that tested positive for MA. Detection rates trended upwards with increased yaba use. No relationship was found between the number of yaba tablets reportedly consumed and the concentration of MA detected in hair.

Conclusions: This study validated a rapid, simple, and economical SPME/GC-MS technique for quantification of MA in hair. The method was less sensitive for quantification of AM.

Background: Although there have been many descriptive studies of diphtheria from resource limited countries, descriptions of the natural history of diphtheritic myocarditis in patients from these countries are scarce.

Objective: To present the natural history of diphtheritic myocarditis from a hospital in northeastern Thailand.

Methods: The clinical features of 38 patients with diphtheria admitted to the Khon Kaen University Hospital in northeastern Thailand between 1983 and 1996 were reviewed.

Results: Of the 38 cases of diphtheria, 10 progressed to diphtheritic myocarditis (26%). Electrocardiographic findings of the 10 patients with myocarditis were myocardial and conduction abnormalities. The presence of a clinically severe (toxic) type (P < 0.001) or a swollen neck (bull neck) (P = 0.001) was a predictor of the occurrence of myocarditis. Five (50%) of the 10 patients with myocarditis had conduction abnormalities (third-degree atrioventricular block 3, left bundle branch block 1, and right bundle branch block 1). Four patients with severe symptomatic bradyarrhythmia (third-degree atrioventricular block 3, and left bundle branch block 1) received ventricular pacing, and 3 patients died after this pacing. Echocardiographic abnormalities of left ventricular dilatation and myocardial hypertrophy were found in all 5 patients with conduction abnormalities. All 6 of 7 survivors of diphtheritic myocarditis had normal 12-lead electrocardiographic results at 1-month follow-up. A patient who was the survivor of third-degree AV block had an electrocardiographic finding of flat T waves, and with a complete echocardiographic normalization of left ventricular dilatation and myocardial hypertrophy.

Conclusion: The present study confirms that increasing diphtheria immunization coverage in the population remains the most important strategy for the control of diphtheria. In resource limited countries, clinical findings, electrocardiography, and sometimes where available, echocardiography are helpful in assessing the severity of diphtheritic myocarditis, decision making of acute management, and predicting fatal outcome.

Background: T`he prevalence of aluminum (Al)-related toxicity in hemodialysis (HD) patients has declined. However, some HD patients continue to receive Al-based phosphate binders, in part because of the expense of Al-free binders.

Objective: To explore the effect of Al-based binders and their discontinuation on iron status, and markers of bone formation resorption in HD patients.

Methods: Following an initial screen of serum Al levels in 37 HD patients, a second screening was performed after discontinuation of Al-based binders in a 2-year follow-up. A desferrioxamine (DFO; 5 mg/kg) test, and assessment of iron status and bone markers were conducted in the second screening.

Results: Mean serum Al level was initially 27.8 ± 10.3 μg/L. Thirteen patients had a serum Al >30 μg/L, a level considered possibly toxic. There was a positive correlation between serum Al levels, HD duration, and cumulative dose of Al-based binder. At the second screening, the mean serum Al level decreased to 12.5 ± 7.4 μg/L. The mean serum Al level increased to 26.0 ± 14.7 μg/L post-DFO, but in none of the patients did the change in serum Al exceed the 50 μg/L threshold associated with Al-induced bone disease. The decrease in serum Al level was associated with a significant increase in intact parathyroid hormone (iPTH) whereas total alkaline phosphatase did not change.

Conclusions: We recommend that if Al-based phosphate binders are used in HD patients, serum Al level, iron, and markers of bone formation resorption be closely monitored to ensure safe use of these drugs.

Background: High plasma B-type natriuretic peptide (BNP) levels in patients with severe chronic heart failure (CHF) often indicate poor ventricular function and poor prognosis. However, in some such patients plasma BNP levels are normal.

Objective: To investigate the clinical implications of BNP levels in patients with severe CHF.

Methods: Fifty-seven patients with severe CHF were divided into group A (13 normal plasma BNP level) and 44 patients (high plasma BNP levels) group B. Diuretics, angiotensin-converting enzyme inhibitors (or angiotensin II receptor antagonist, e.g., metoprolol) and digitalis were used as conventional treatment. The clinical characteristics of all patients in two groups were analyzed and compared.

Results: At the first admission, left ventricular end diastolic diameter in group B was significantly lower than group A (p < 0.05), and the plasma BNP level in group B was significantly higher than group A (p < 0.05). When metoprolol was used, 6 and 5 patients in group A and B could not tolerate the initial dose. In other cases using metoprolol at average maximum tolerance dose of metoprolol 12.5-6.25 and 24.20-11.22 mg/day in group A and B, respectively, there was a significant difference between them (p < 0.05). There were no significant differences in plasma BNP levels between two groups during stable period. The plasma BNP level in group B during acute worsening stage was significantly higher than in the remission stage (962.73-165.00 ng/L vs 876.24-167.70 ng/L, p < 0.05). However, there was no significant difference between group A (74.03-11.18 ng/L) and group B (71.38-11.68 ng/L) (p > 0.05). The mobility of group A was higher than group B (11/12 vs 6/44, p < 0.05). Logistic regression analysis showed that, the plasma BNP level was the independent risk factor for predicting cardiac death (regression coefficient, 3.817; OR, 45.488; 95% CI, 5.322ʺ388.791).

Conclusion: In patients with severe CHF, normal plasma BNP level suggests depletion of BNP secretion and further deterioration of cardiac function, indicating a poor prognosis.

Background: RH genotyping studies have been conducted mainly in people of Caucasian and African descent. There is limited information regarding the molecular basis for RH genotypes in Malaysia.

Objectives: To investigate the prevalence and characteristics of RHCE genotypes among different ethnic groups in Malaysia.

Methods: A total of 1014 whole blood samples were obtained from donors from 4 different ethnic groups (360 Malays, 434 Chinese, 164 Indians, and 56 others). All samples were phenotyped for C, c, D, E, and e using standard serologic methods and genotyped using polymerase chain reaction (PCR)-based analysis.

Results: In the blood samples that we analyzed, the distribution of RH genotype antigens was significantly different among the various ethnic groups. Our findings showed that CCDee is the most common in Malaysian blood donors; 18.4% (187/1014) compared with other genotypes. The ccDEE genotype is more prevalent in the Chinese: 65.6% (82/125), and the ccee genotype is more prevalent in Indians: 47.1% (65/138). There were discrepancies between phenotypes and genotypes. There were 17 (1.7%) discrepancies in RH C/c genotyping results and of these 47% (8/17) occurred in Malays. Discrepancies in RH E/e results occurred in 3 samples (0.3%).

Conclusions: Our study provides a database for the distribution of RH genotypes of donors from the major ethnic groups in Malaysia. Methods used in this study are useful for comparing the phenotypes and genotypes. Further investigation should be conducted to study the causes of these discrepancies using other molecular based techniques.

Background: A 100-g oral glucose tolerance test (OGTT) is commonly used to diagnose gestational diabetes mellitus (GDM). Carpenter-Coustan (CC) criteria, based on lower threshold plasma glucose values than the National Diabetes Data Group (NDDG) criteria, result in an apparently increased prevalence of GDM. However, the extent of the increase is not known, and effects on perinatal outcome are not clear.

Objective: To evaluate the increase in the prevalence of GDM if CC criteria are applied to OGTT results, we compared findings with NDDG criteria. Pregnancy outcomes between women without GDM and those with GDM diagnosed by NDDG and CC criteria were compared.

Methods: A total of 640 at-risk pregnant women were studied. They were either diagnosed as having GDM by initial testing (145 women), or repeat testing at 24−28 weeks of gestation (495 women). CC criteria were applied to the OGTT results and prevalence of GDM was re-evaluated.

Results: The apparent prevalence of GDM increased by 22.2% using CC criteria. The change was 27.6% at the initial test and 31.5% at repeat tests during 24−28 weeks of gestation. Infant birth weight in GDM diagnosed by either NDDG or CC criteria was significantly higher than in the negative OGTT group (P < 0.001). Rates of macrosomia were comparable. Neonatal hypoglycemia was 14.6% in the NDDG group, 8.2% in CC only group, and 4.6% in negative OGTT group (P < 0.001).

Conclusion: The CC criteria identify 22% more cases of GDM than NDDG criteria during initial and repeat tests.

Background: Gynecomastia is a common benign lesion of the male breast and accounts for up to 80% of male patients referred with beast lesions.

Objective: To examine the pattern of breast lesions in male patients who underwent breast biopsy.

Methods: All male patients referred to Hatyai Hospital with breast complaints were included in the study. Histopathology reports were retrospectively reviewed during 2004-2011.

Results: In 77 male patients diagnosed with breast lesions, the most common lesion was gynecomastia (49/77, 64%), followed by fibrocystic changes (7/77, 9%), and breast cancer (6/77, 8%). Gynecomastia was commonly found in male patients less than 40 years of age, while other breast lesions are seen in male patients over 40 years of age (P = 0.036, OR = 2.842, 95% CI = 1.085-7.447).

Conclusion: Gynecomastia was the most common diagnosis among breast lesions in male patients referred to the Hatyai Hospital during 2004-2011. Gynecomastia was more common in the patients less than 20 years old.

Background: The sentinel lymph node (SLN) is the first lymph node to receive lymphatic drainage from a primary breast tumor. If the SLN contains no metastatic tumor, then it is unlikely other lymph nodes will contain breast cancer metastasis. When the SLN does contains metastasis, an axillary lymph node dissection (ALND) is recommended to further stage the axilla and to maintain locoregional control. SLNs can be identified by using a dye, radioisotope, or combined techniques.

Objective: To determine the rate of SLN identification using isosulfan blue dye in breast cancer patients at Charoenkrung Pracharak Hospital, Thailand, and factors that affect it.

Methods: This prospective study of 106 consecutive cases breast cancer enrolled 105 women (1 bilateral breast cancer case) between October 2011 and October 2013 at Charoenkrung Pracharak Hospital. Clinical and pathological features were analyzed for the effectiveness of SLN identification using isosulfan blue dye.

Results: The rate of SLN identification using isosulfan blue dye in breast cancer patients at Charoenkrung Pracharak Hospital was 92%. The method was safe and well tolerated in early-stage breast cancer patients.

Conclusion: The effectiveness of sentinel node identification using isosulfan blue dye in breast cancer patients at Charoenkrung Pracharak Hospital is consistent with that shown in studies from other countries.

Background: Hip fracture seriously influences an elderly person’s life and mobility, independent living, and causes earlier mortality. Although surgery is generally successful, many of the elderly suffer from decreased physical ability after surgery for hip fracture.

Objectives: To determine the effects of a physical activity enhancing program (PEP) on the level of physical activity of elderly patients after surgical treatment of hip fracture.

Methods: A randomized controlled trial of 46 elderly patients was conducted at King Chulalongkorn Memorial Hospital from January 2012 to February 2013 to evaluate the effectiveness of the Resnick self-efficacy model (2009) compared with standard care in improving physical activity. The participants were enrolled on a criteria basis and were block randomized into two groups. The intervention group attended four phases of physical training and efficacy based intervention comprising assessment, preparation, practicing, and evaluation phases with face-to-face contact and five telephone calls during seven weeks post-surgery.

Results: Six weeks after discharge, the physical activity of the intervention group increased by significantly more than the control group (F_1,43 = 9.63, P < 0.01), with an effect size of 0.18 after controlling for preoperative physical activity. The ratio of the effect on physical activity induced by the PEP was higher than that induced by usual care (65.2% vs. 47.8%).

Conclusion: PEP is effective at improving physical activity. Efforts to follow up for longer periods and with studies using larger populations are recommended.

Background: Laparoscopic adrenalectomy (LA) is the preferred approach to adrenal gland tumors.

Objective: To evaluate the perioperative and functional outcomes of transperitoneal LA.

Methods: We retrospectively reviewed data of all consecutive patients who underwent transperitoneal LA at our institution between April 2000 and December 2011.

Results: Two hundred two patients with mean age of 46 years were included in the study. There were 109 left, 89 right, and 4 bilateral tumors. Preoperative diagnosis included 126 aldosterone-producing adenomas (APA), 33 patients with Cushing syndrome, 19 pheochromocytomas, 20 nonfunctional tumors, and 4 adrenal metastases. Mean tumor size was 3.3 cm (range 0.4-22 cm). Mean operative time was 109 min and estimated blood loss 90 mL for unilateral adrenalectomy; and 195 min and 300 mL for bilateral adrenalectomy. Four patients with pheochromocytoma required transfusion and 2 required conversion to an open approach. Seven intraoperative complications and 18 30-day postoperative complications occurred. These included 5 major complications (Clavien-Dindo grade 3-5). Ninety-seven percent of APA patients had normal serum potassium levels after surgery. Among the patients with functioning endocrine tumors, complete resolution rate from secondary hypertension was significantly higher in the pheochromocytoma group compared with those with APA or Cushing syndrome (82% vs. 48% vs. 68% respectively, p = 0.02). Mean follow up was 35.2 months.

Conclusion: LA is the treatment of choice for most adrenal gland tumors with excellent outcomes and low complication rates. There was a high chance for complete resolution of secondary hypertension after surgery for pheochromocytoma.

Background: Medication nonadherence is common in elderly patients and is a major cause of morbidity. However, it is not well-described in the literature and to our knowledge has never been studied in Thais.

Objective: To investigate the extent, causes, and contributing factors of medication nonadherence in older patients in a geriatric clinic.

Material and Methods: We conducted a cross-sectional study at Siriraj Hospital, a university teaching hospital in Bangkok. We assessed baseline demographic data, comorbid diseases, Thai Mental State Examination (TMSE), functional status (basic and basic activities of daily living), type and number of medications used, and medication adherence.

Results: There were 153 participants in this study. Medication nonadherence, in the administration of prescribed drugs only, was found in 34% of the participants. Nonadherence to administration of prescribed drugs and to the advice regarding over-the-counter drugs was 42.5%. Nonadherence to the administration of prescribed drugs and to the advice regarding over-the-counter drugs, and herbal and dietary supplements was 54.9%. Three most common causes of medication nonadherence were misunderstanding or lack of the knowledge (25.6%), the development of adverse drug events (18.9%), and because of a suggestion by a friend or family member (16.2%).

Conclusion: Medication nonadherence is common in elderly Thais attending geriatric clinics. We recommend clinicians be aware of this problem and develop a system to improve medication adherence. The clarification of reasons for prescribing is crucial. We recommend emphasis on educating patients, family members, and the public about the risk of nonadherence and of using nonprescribed medications.

Background: Kodály approach is one of widely used methods in music education and music therapy. The method is based on singing activities that could facilitate young children’s social development. Thus, the application of Kodály approach may be appropriate to enhance the joint attention behaviors of children with autism.

Objective: We examined the joint attention of individuals with autism spectrum disorders (ASD) during Kodály-based music experiences.

Methods: The A-B-C-B single-case design was employed to investigate the effectiveness of Kodály-based music experiences on joint attention behaviors of three children, ranging from 7.8 to 11.5 years of age, with autism who had manifested joint attention problems. The experimental sessions consisted of baseline condition (A), group intervention (B), and individual invention session (C). The SCERTS assessment process (SAP) was used to measure joint attention behaviors. The findings were presented using visual inspection.

Results: During baseline sessions, the three participants rarely engaged in joint attention with others. Their behaviors were stable during the first three sessions, with mean occurrence of 5, 9.3, and 4. In the course of the music intervention, they positively responded to the intervention. The frequencies of their behaviors continuously increased from the first group intervention sessions until the second group intervention sessions. Finally, the second group intervention sessions showed that most of the data points were above the mean of all previous sessions, with mean occurrence of 43.8, 34.1, and 18.8.

Conclusion: The Kodály approach was found one of useful methods in music education that can apply to music therapy to enhance joint attention behaviors of the children with autism. The children were able to learn how to engage in a group setting through singing activities, folk music, and solfège learning.

Background: Hypoadiponectinemia and hyperleptinemia, and reductions in the ratio of adiponectin to leptin (A/L ratio) are associated with the development of hepatic necroinflammation in nonalcoholic fatty liver, but the association of the adipokines with hepatic steatosis in chronic viral hepatitis is unclear.

Objective: To investigate the relationship between serum A/L ratio, insulin resistance, degree of hepatic steatosis, and necroinflammation in patients with chronic viral hepatitis.

Methods: We measured serum adiponectin, leptin, and resistin levels, insulin resistance, and analyzed the association between liver histopathology and the level of the adipokines in 44 patients with chronic viral hepatitis before they started treatment.

Results: We found that insulin resistance, leptin, and resistin levels tended to increase in the group with a greater degree of hepatic steatosis and necroinflammation, but that the increase was not significant. The adiponectin/leptin ratio (A/L ratio) in a group with a low degree of hepatic steatosis was significantly higher than it was in the group with a high degree of hepatic steatosis (3.1 ± 3.1 vs 1.2 ± 0.8; P = 0.008). The A/L ratio in a group with low histological activity index (HAI) scores was significantly higher than in the group with high HAI scores (3.7 ± 3.4 vs 1.1 ± 1.1; P = 0.006). Abdominal obesity was the only variable that showed a significant association with the HAI score (P = 0.03).

Conclusion: The serum A/L ratio in patients with chronic viral hepatitis showed a significant inverse association with their degree of hepatic steatosis and necroinflammation.

Background: Bilateral lateral rectus recession is the most common surgical treatment of intermittent exotropia in children. Success rates in previous studies differ because longer follow-up periods may change success rate as the eyes drift out with time. Initial overcorrection was thought to be appropriate management, but the preferred initial postoperative deviation has not been well quantified.

Objective: To study long-term outcomes (≥3 years) of bilateral lateral rectus recession for intermittent exotropia and to evaluate factors influencing long-term success.

Methods: This retrospective descriptive study reviews patients with intermittent exotropia who underwent bilateral lateral rectus recession with a minimum follow up of 3 years. Long-term motor outcome was classified as good (within 8 prism diopters (PD) of esodeviation and 10 PD of exodeviation), acceptable (exodeviation 11-20 PD), and poor (esotropia >8 PD or exotropia >20 PD). Stereoacuity testing pre- and postoperatively was used to evaluate sensory outcome. Correlation between long-term outcome and various pre- and postoperative factors were analyzed.

Results: A total of 59 patients met the selective inclusion criteria. The mean age at time of surgery was 7.1 years with a mean follow-up time of 4.5 years. At the time of the last visit, 69% (41 patients) had good outcomes, 24% (14 patients) had acceptable outcomes, and 7% (4 patients) had poor outcomes. Initial postoperative ocular deviation significantly correlated with long-term outcome (P < 0.05). Mean initial postoperative ocular deviation of patients with good outcome was esodeviation 12.7 PD (range ortho to esodeviation 25 PD). In 45 patients whose stereoacuity could be assessed, 58% (26 patients) had stereoacuity improvement.

Conclusion: Good long-term motor outcome can be achieved in 69% of patients following bilateral lateral rectus recession for intermittent exotropia. Initial postoperative ocular deviation correlated with long-term motor success.

Background: Longitudinal deficiency of upper limbs with oligodactyly is a very rare congenital malformation. It manifests itself as preaxial or postaxial hypoplasia/aplasia of long bones accompanied by reduction of palm and phalanges.

Objective: To report two cases with essentially similar phenotypic presentation characterized by unilateral mesomelic shortening of limb, ulnar hypoplasia, and severe deficiency of skeletal elements of hand that were found in unrelated individuals.

Methods: Review of clinical and family history, phenotypic examination, physical and radiological investigations, and literature review.

Results: In both individuals, the right arm was short, the size of the middle arm and hand being dramatically reduced in size, and the hand comprising only two functional digits. Roentgenograms revealed hemimelia/ dysmelia of the ulna, hypoplasia of radius, dysplastic distal radial head, and several missing carpals. Only two phalangeal rays were witnessed in the hand. Radiographic measurements showed a normal contralateral arm and lower limbs, and no other associated symptoms. These phenotypes were classified as type I and type D according to the schemes proposed by Swanson et al., and Ogino and Kato, respectively. Both individuals were the product of third degree consanguineous unions (F = 0.0625).

Conclusion: Consistent phenotypic pattern of longitudinal limb anomalies evident in two independent subjects suggest a common underlying genetic etiology. There is currently no known genetic factor to allow molecular testing and risk estimation for family members. Isolated limb anomalies may provide important clues to understand pathomorphogenetic mechanisms that lead to the disruption of normal limb development.