Medical Journal of Indonesia

Moving forward without leaving the ethical standard of publication

Agus Rizal Ardy Hariandy Hamid — 2019-05-08

[no abstract available]

Upregulation of FGFR3 and HIF-1α expression in muscle invasive bladder cancer

Syah Mirsya Warli — 2019-05-08

BACKGROUND The major risks in patients diagnosed with non-muscle invasive bladder cancer (NMIBC)are recurrence, progression of muscle invasive bladder cancer (MIBC), and metastasis. Biological markers such as fibroblast growth factor receptor-3 (FGFR3) and hypoxia-inducible factor-1α (HIF-1α) are related to muscle invasiveness of bladder cancer. This study was aimed to analyze the expression of FGFR3 and HIF-1α to predict muscle invasiveness in bladder cancer patients.

METHODS This was an observational study with a case-control design. Sixty patients with bladder cancer, who underwent histopathology examinations at the Department of Pathology, Faculty of Medicine, Universitas Sumatera Utara/H. Adam Malik Hospital from January 2012 to December 2015, were included in this study. Samples were then classified into 30 NMIBC and 30 MIBC groups. All samples were analyzed with an immunohistochemistry assay for FGFR3 and HIF-1α. H-scores were used to determine the relationships between each group.RESULTS FGFR3 was expressed in 29 (96.7%) patients of the NMIBC group, and 23 (76.7%) patients of the MIBC group (p=0.026, OR=8.8; 95% CI=1.01–76.96). HIF-1α was expressed in only 1 (3.33%) patient of the NMIBC group, and 15 (50%) patients of the MIBC group (p<0.001, OR=29; 95% CI=3.49–241.13).

CONCLUSIONS There was a difference in upregulation of FGFR3 and HIF-1α expression in both the NMIBC and MIBC groups.

Effect of reperfusion injury from distant ischemia to small intestine

Yefta Moenadjat — 2019-05-08

BACKGROUND The ileum is the most vulnerable part of the small intestine that plays an important role as the motor of multisystem organ failure. Villous damage is demonstrated after ligation of supply artery in mice; however, there is no study on the ileum after distant ischemic organs. Thus, this study was aimed to find out ileal villous changes following reperfusion injury, the protective effects of ischemic hypothermia and ischemic preconditioning.

METHODS An experimental study conducted enrolled 21 subjects of Oryctolagus cuniculus. Ischemia is induced by ligation of the femoral artery for 4 hours. Eight hours after ligation was released, ileum and duodenal specimens were taken through laparotomy. H&E stained specimens were examined for histomorphological changes. Villi change scores, tissue level of hypoxia-inducible factor-1α (HIF-1α), malondialdehyde (MDA), and occludin were statistically analyzed in four treatment groups, namely ischemia, ischemic hypothermia, ischemic preconditioning, and control.

RESULTS Intestinal villi changes were found following ischemic-induced arterial ligation. Ileal villi changes showed differences with the duodenum and controls as indicated by the villi damage scores, increased tissue HIF-1α and MDA, and decreased occludin levels. Ileal villi changes in the ischemic and ischemic hypothermia groups showed significant changes with controls; whereas the ischemic preconditioning group showed no significant differences.

CONCLUSIONS Ischemia at a distance leads to both histomorphological and biochemical damage of the ileal villi and disrupts the integrity of the intestinal mucosal barrier. In addition, the study showed a protective effect of ischemic preconditioning.

Efforts to overcome hypoxia condition in Balb/c mouse macrophages after intraperitoneal SRBC immunization

Pungguri Ayu Nega Sarsanti — 2019-05-08

BACKGROUND Activated macrophages require increased oxygen to destroy foreign bodies, leading to an increase in the levels of reactive oxygen species (ROS). Therefore, macrophages would experience hypoxic and oxidative stress conditions at the same time. Thus, this study was aimed to evaluate the mechanism of the activated macrophages to overcoming this dual condition.

METHODS The activated macrophages were harvested from the intraperitoneal cavities of 18 BALB/c mice immunized with 2% sheep red blood cells (SRBCs). The macrophage suspension was divided into four groups: control, 24, 48, and 72 hours after-immunization groups. The expressions of hypoxia-inducible factor (HIF)-1α, HIF-2α, and cytoglobin (Cygb), as markers for hypoxic condition, were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), whereas peroxisome proliferator-activated receptor gamma coactivator (PGC-1α) protein as a marker for mitochondrial biogenesis and aerobic metabolism was measured with ELISA. The analysis of oxidative stress was conducted with the water-soluble tetrazolium salt test.

RESULTS The HIF-1α mRNA expression was the highest at 24 hours, whereas the HIF-2α mRNA showed no increased expression during the observation. The Cygb mRNA decreased after 24 hours. The highest expressions of HIF-1α and HIF-2α proteins were detected at 72 hours, whereas the Cygb protein expression increased since 24 hours. The PGC-1α protein expression increased at 72 hours. The WST test showed the highest ROS level at 24 hours.CONCLUSIONS The macrophages were activated by SRBCs underwent dual hypoxia and oxidative stress condition simultaneously to overcome the foreign bodies. The macrophages overcame these stress conditions by increasing their aerobic metabolism.

The susceptibility of pathogens associated with acne vulgaris to antibiotics

Irma Bernadette Simbolon Sitohang — 2019-05-08

BACKGROUND Acne vulgaris is a pilosebaceous disorder. Bacterial activity and inflammation both influence acne formation. Antibiotics suppress the bacterial activities and elicit anti-inflammatory effects. The overuse of antibiotics may lead to resistance in bacteria. This study was aimed to provide an overview of bacteria that may cause acne and determine their susceptibility to antibiotics.

METHODS This was a cross-sectional study sampling from 93 patients with acne in Ciptomangunkusumo Hospital. Comedones were extracted and cultured on Brucella blood agar, under aerobic and anaerobic conditions at 35^oC for 24–48 hours. Bacterial identification was performed using Vitek®, and susceptibility test using E-test. Data interpretation was based on the Clinical and Laboratory Standards Institute 2015.

RESULTS Staphylococcus epidermidis (50.5%), Propionibacterium acnes (11.0%), and Staphylococcus aureus (7.7%) were identified. Bacteria were not found in 69.2% and 1.1% of samples in anaerobic and aerobic cultures, respectively. P. acnes was susceptible to doxycycline (100%) and minocycline (100%), while 10% was resistant to erythromycin, clindamycin, and tetracycline. S. epidermidis was susceptible to minocycline (100%); but resistant to erythromycin (65.2%), clindamycin (52.2%) and tetracycline (32.6%). The susceptibility of S. epidermidis to doxycycline was 89.1%, which was lower than that of P. acnes (100%). S. aureus was found to be sensitive to minocycline (100%), doxycycline (71.4%), clindamycin (71.4%), and tetracycline (71.4%); but it was resistant to erythromycin (42.9%).

CONCLUSIONS Doxycycline and minocycline showed 100% effectiveness for P. acnes. The isolated bacteria were more susceptible to doxycycline compared to tetracycline. The use of clindamycin and erythromycin needs to be limited as most S. epidermidis isolates were resistant to both.

Incidence and short outcome in multiple pregnancies: a single center cross-sectional study in Iran 2016–2017

Behnaz Basiri — 2019-05-08

BACKGROUND The incidence of multiple pregnancies in industrialized countries due to the use of assisted reproductive techniques has increased over the past two decades. Multiple births are more dangerous than single pregnancies for mother and baby. This study evaluated the frequency of multiple pregnancies and its neonatal complications.

METHODS In this cross-sectional study, we assessed all multiple neonates hospitalized in Fatemieh Hospital of Hamadan, Iran from September 2016 to September 2017 in terms of gender, gestational age, birth weight, the use of assisted reproductive techniques, delivery method, cause of hospitalization, therapeutic intervention, and hospitalization outcome.

RESULTS Of 10,581 deliveries during the study period, 351 (3.3%) was multiple pregnancies and 232 neonates hospitalized. The incidence of twin, triplet, and quadruplet birth were 1.7%, 0.39%, and 0.11% respectively. In this study, 178 twin and 54 triplet and quadruplet birth were compared. The mean gestational age and mean birth weight of triplet and quadruplet were lower than that of twin births (p<0.001). A significant difference was found on the frequency of assisted reproductive techniques (p<0.001). Female sex (p=0.007), lower mean gestational age (p=0.009), lower mean birth weight (p=0.017) and need to mechanical ventilation (p<0.001) were significantly associated with early neonatal death in multiple pregnancies.

CONCLUSIONS The incidence of multiple births was high in the Hamadan province, which was often followed by infertility treatment. Moreover, multiple births cause prematurity, low birth weight, respiratory distress syndrome, and increased neonatal mortality rate.

Survey frequency of the depression and anxiety levels of infertile women in western Iran

Shoboo Rahmati — 2019-05-08

BACKGROUND Infertility among couples is a painful emotional problem, which results in the feeling of grief in the form of psychological problems such as depression and anxiety. The present study was aimed to survey the frequency of depression and anxiety levels of infertile women in western Iran in 2017.

METHODS This cross-sectional study used a simple random sampling method for selecting the sample. The study population consisted of all infertile women who went to Farhangian health center in Ilam. The Beck’s Depression Inventory, Beck’s Anxiety Inventory, and demographic characteristics questionnaire were used for collecting the data. The questionnaires were distributed among midwife experts and patients. The collected data were analyzed by the chi-square test and variance analysis using SPSS version 20.

RESULTS Among 200 infertile women, 53.5%, 32%, 11%, and 3.5% suffered from severe, moderate, mild, and no anxiety, respectively. However, 96.5% suffered from various degrees of anxiety with 85.5% from clinical anxiety. In addition, 42%, 19.5%, 14.5%, and 24% suffered from severe, moderate, mild, and no depression, respectively. However, 76% suffered from various degrees of depression with 61.5% from clinical depression. There is a significant relationship between the education level of husbands, education level of women, and type of infertility (p<0.05). Women who had a lower than diploma education level and primary infertility suffered from higher anxiety levels.

CONCLUSIONS There was a high level of anxiety and depression in infertile women; therefore, it is necessary to pay attention to these disorders in the process of treatment of infertile women.

Low estradiol levels escalate menopausal symptoms leading to mild cognitive impairment in postmenopausal women

Andon Hestiantoro — 2019-05-08

BACKGROUND Women in menopause experience dramatic alterations in gonadal hormone concentrations, including diminished estradiol levels. It has been hypothesized that these hormonal changes may be responsible for the occurrences of menopausal symptoms, such as hot flushes, sleep disruption, night sweats, and irritability, as well as mild cognitive impairment (MCI) in postmenopausal women. Therefore, this study was aimed to determine if there is any association between hormonal changes and menopausal symptoms, including MCI in postmenopausal women.

METHODS A total of 245 postmenopausal women were recruited for this cross-sectional study and classified into 2 groups; MCI and non-MCI groups. Diagnosis of MCI was made using the modified Petersen criteria. Variables such as subjects’ age, duration of menopause, menopausal symptoms, anthropometric status, hormone levels, and cognitive status were assessed and statistically analyzed.

RESULTS Of the 245 subjects enrolled in this study, 53.9% had MCI. Multivariate analysis found that sleep disruption and estradiol levels were independent risk factors of MCI in postmenopausal women. No significant correlation was found between menopausal symptoms and estradiol concentration.

CONCLUSIONS Low estradiol levels were associated with higher risks of experiencing menopausal symptoms and MCI. Sleep disruption and estradiol levels were the most influential factors in the development of MCI in postmenopausal women.

DiabCare Asia 2012: diabetes management, control, and complications in patients with type 2 diabetes in Indonesia

Achmad Rudijanto Cholil — 2019-05-08

BACKGROUND Indonesia was a part of the most recent edition of DiabCare Asia held in 2008. DiabCare Asia 2012 is modeled after a similar project to provide the latest information to facilitate healthcare policymaking in this area.

METHODS This was an observational, non-interventional, cross-sectional study of patients with type 2 diabetes mellitus from primary, secondary, and tertiary care centers in Indonesia. Patient data collected included demography, medical history complications, eye and foot examinations, diabetes management, and most recent laboratory investigations. Blood samples were collected from all patients for the analysis of glycated hemoglobin (HbA1c).

RESULTS A total of 1,967 patients participated in the study, with a mean (SD) age of 58.4 (9.5) years and a median (range) duration of diabetes 6.0 (0.1−47.0) years. The percentage of patients with HbA1c <7.0% was 30.8% and the mean (SD) HbA1c level was 8.3 (2.2%). The proportion of patients using insulin was 34.7% with a mean (SD) total daily dose of 37.9 (24.1) IU. The most common diabetes-related complications were peripheral neuropathy (59.1%), erectile dysfunction (32.4%), and eye complications (29.1%).

CONCLUSIONS Glycemic and metabolic control remain unsatisfactory in type 2 diabetes patients in Indonesia. Efforts are needed to optimize control and prevent complications in these patients.

Risk of small for gestational age babies in preterm delivery due to pregnancy-induced hypertension

Rima Irwinda — 2019-05-08

BACKGROUND Pregnancy-induced hypertension (PIH) causes high maternal morbidity and mortality worldwide. This study aims to assess the impact of PIH on fetal growth according to gestational age in preterm deliveries.

METHODS A prospective cohort study using secondary data was undertaken in Ende District, East Nusa Tenggara, Indonesia from September 2014 to August 2015. The t-test was performed to compare mean birth weight based on gestational week between normotensive and PIH women, continued by linear regression. The chi-square or Fisher exact test was also conducted to determine the probability of birthing small for the gestational age (SGA) and large for gestational age (LGA) babies between normotensive and PIH women.

RESULTS A total of 1,673 deliveries were recorded in Ende Hospital over the 1-year study period, among which 182 cases involved preterm births. The PIH group had lower birth weight than normotensive women at each gestational age starting from 32–35 weeks (p=0.004; 95% CI 150.84–771.36). Normotensive women at gestational ages of 32 (p=0.05; 95% CI 0.01–0.83), 34 (p=0.37; 95% CI 0.01–4.12), and 36 (p=0.31; 95% CI 0.02–2.95) weeks had a lower risk of birthing SGA babies than PIH women; LGA babies were recorded at gestational ages of 33 (p=1.00; 95% CI 0.07–37.73) and 35 (p=0.31; 95% CI 0.34–63.07) weeks.

CONCLUSIONS Poor perfusion of the uteroplacental is one of the reasons behind intrauterine growth restriction, which results in SGA babies born to PIH women.

CD133, CD44, and ALDH1A1 as cancer stem cell markers and prognostic factors in epithelial ovarian cancer

Nugraha Utama Pelupessy — 2019-05-08

BACKGROUND Ovarian cancer is a heterogeneous disease, and most patients are diagnosed at an advanced stage. Epithelial ovarian cancer type II is characterized by rapid tumor growth and is genetically more labile than type I. This study was aimed to demonstrate the prognostic value of CSC by using the markers CD133, CD44, and ALDH1A1 in EOC.

METHODS Clinicopathological and demographic data were collected from medical records. The markers CD133, CD44, and ALDH1A1 were examined with flow cytometry and immunohistochemistry. Cancer stem cell (CSC) marker expression in patients with ovarian cancer types I and II were related to chemotherapy and survival. In multivariate analysis, the prognosis model was tested for ten months.

RESULTS The largest demographic consisted of patients aged ≥45 years, with stage I, poor differentiation, and type II, of which there were 40 samples (72.7%), 23 samples (41.8%), 30 samples (54.5%), and 16 samples (29.1%), respectively. There is a high correlation between the 10-month chemotherapy response and the 4 variables, i.e., age ≥45 years, type II, stage III–IV, and CD44, with an ROC of 80.75% and a post-test probability of 82.5%. Using the ROC curve, the highest chemoresistance score was 0.841, based on the combination of CSCs markers and clinicopathological factors, that is stage III–IV, age ≥45 years, poor differentiation, type II, negative CD133, high CD44, and high ALDH1A1.

CONCLUSIONS CSC (CD133, CD44, and ALDH1A1) markers and clinicopathological factors are prognostic of epithelial ovarian cancer.

Daily consumption of growing-up milk is associated with less stunting among Indonesian toddlers

Damayanti Rusli Sjarif — 2019-05-08

BACKGROUND In Indonesia, animal protein intake in children is low and might contribute to a high prevalence of stunting. This study was aimed to evaluate the association between animal protein source consumption and stunting in toddlers.

METHODS This cross-sectional study obtained secondary data from the Ironcheq questionnaire validation study to detect the risk of iron deficiency in toddlers. The Ironcheq study was carried out in five integrated health service posts (Posyandu) in Jakarta from 2013 to 2014. Data from 172 subjects, consisting of 41 stunted (height-for-age z-score less than -2) and 131 normal children, were analyzed to evaluate the association between animal protein source consumption and stunting using multivariate logistic regression test.

RESULTS Stunted children tend to come from a family with low parental education and socioeconomic status. Consuming growing-up milk (GUM) ≥300 ml/day was protective against stunting (adjusted OR 0.28, 95% CI 0.13–0.63), whereas consuming red meat product ≥5 times/week was a risk factor (crude OR 3.70, 95% CI 1.17–11.74), however after adjusted to age, sex, and other variables in the questionnaire, the OR was not significant (adjusted OR 3.64 95% CI 1.00–13.26).

CONCLUSIONS A daily consumption of 300 ml of GUM may be considered to prevent stunting in toddlers. Red meat products (sausage, nugget, and meatball), which are commonly consumed because of its practicality, could not be considered as significant animal protein sources because of a wide variation of their nutritional content.

Lepromatous leprosy mimicking systemic lupus erithematosus: a case report

Niken Kusumaningrum — 2019-05-08

The clinical manifestations of leprosy are highly variable, and the disease is notorious for being “a great imitator” of several other conditions. Leprosy may manifest with a variety of phenomena resembling those of autoimmune diseases. Herein, we report a 33-year-old male presenting with wounds on his left leg and hyperpigmented skin lesions all over his body. Six years earlier, the patient was diagnosed with systemic lupus erythematosus (SLE). However, therapy for SLE did not control his symptoms; instead, the patient developed features of leprosy, such as anesthetic skin lesions, nerve enlargement, and tenderness. Tests for antinuclear antibodies and anti-double stranded DNA antibodies were negative. Slit-skin smear showed a bacterial index of 6+ and morphological index of 10 %. Lupus band test results were negative. Histological findings were compatible with lepromatous leprosy. The clinical and serological similarities between leprosy and SLE may lead to erroneous diagnosis. Thus, clinicians should be aware of this characteristic for correct diagnosis.

Internet addiction: a new addiction?

Kristiana Siste Kurniasanti — 2019-05-08

The internet today has become an integral part of daily life that facilitates communication, education, and entertainment. The behavioral pattern of excessive internet usage has similarities to substance addiction, such as tolerance, withdrawal, repeated failure to reduce or quit, and impairment in daily life. Yet, there is no consistent physiological change that accompanies excessive use of the internet, as there is in excessive substance use. Neurological and neuroimaging studies of excessive internet users show biological changes in the prefrontal cortex that are similar to those found in other addictive syndromes. Brain structure changes also occur in the temporal cortex and ventral striatum, compromising executive function in planning and reasoning and increasing impulsive risk, resulting in loss of control over internet use. Of all the potential online applications known to cause addiction, only internet gaming disorder has been selected in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) as a condition for further study.

The potential of carbonate apatite as an alternative bone substitute material

Ahmad Jabir Rahyussalim — 2019-05-08

Bone reconstructive surgery has become a common procedure, and bone transplantation has become the second most frequently performed tissue transplantation procedure worldwide. Therefore, the need for bone substitute materials has increased. Artificial bone substitutes exhibit osteoconductive properties and feature several advantages, including abundant resources, low cost, and low donor site morbidity. Carbonate apatite (CO3Ap) is a calcium phosphate ceramic that can be used as a synthetic bone graft. The carbonate content of this ceramic is similar to that of bone apatite. In this review, we show that carbonate apatite can be degraded given its chemical reactivity in a weakly acidic environment and through osteoclast resorption. Moreover, it is osteoconductive and promotes bone tissue formation without fibrotic tissue formation. Additionally, microstructural analysis revealed that new bone tissue is formed within the bone graft itself.