1.Teratogenic effects of the anticonvulsant gabapentin in mice.
Prakash ; L V PRABHU ; R RAI ; M M PAI ; S K YADAV ; S MADHYASTHA ; R K GOEL ; G SINGH ; M A NASAR
Singapore medical journal 2008;49(1):47-53
INTRODUCTIONWe aim to study and elucidate the safety profile of the antiepileptic doses of gabapentin during pregnancy, and to evaluate gabapentin-induced murine fetotoxicity at different dose levels.
METHODSA total of 60 pregnant mice, divided into 12 groups of five mice each, were exposed to gabapentin in four different doses of 0 (control), 113, 226, or 452 mg/kg body weight per day, at three different gestational stages including early gestation (1-6 days), mid-gestation (7-12 days), and late gestation (13-17 days). The pregnant mice were euthanized on day 18 of gestation, and foetuses were examined for teratogenic manifestations. Their brains were dissected and examined for gross changes, malformations, histological changes, and quantitative protein estimation.
RESULTSFoetal resorptions were observed in all treated groups with gabapentin administration at early gestation (1-6 days), and mid-gestation (7-12 days). On the other hand, growth retardation along with stunting in size of live foetuses were observed in all the mid-gestation (7-12 days), and late gestation (13-17 days) treated groups. Various gross malformations were observed with all the three doses (113, 226, and 452 mg/kg body weight per day) when gabapentin was administered at mid-gestation (7-12 days). The same trends were confirmed by gross and microscopic examination of brains along with quantitative protein estimation.
CONCLUSIONGabapentin should not be prescribed during pregnancy, as no therapeutic dose of gabapentin is safe during this period as far as the foetal well-being is concerned.
Abnormalities, Drug-Induced ; Amines ; adverse effects ; Animals ; Anticonvulsants ; adverse effects ; Body Weight ; Congenital Abnormalities ; prevention & control ; Cyclohexanecarboxylic Acids ; adverse effects ; Dose-Response Relationship, Drug ; Female ; Mice ; Mice, Inbred ICR ; Models, Chemical ; Pregnancy ; Pregnancy, Animal ; drug effects ; Teratogens ; gamma-Aminobutyric Acid ; adverse effects
2.A variation of the phrenic nerve: case report and review.
Prakash ; L V PRABHU ; S MADHYASTHA ; G SINGH
Singapore medical journal 2007;48(12):1156-1157
During routine dissection in the department of anatomy, the following anatomical variations of the phrenic nerve were observed on the right side of the neck of a 30-year-old male cadaver. The phrenic nerve, in its early course close to its origin, gave a communicating branch to the C5 root of the brachial plexus. At the level of the root of neck just before entering the thorax, the phrenic nerve was located anterior to the subclavian vein. This unique case of phrenic nerve variation gains tremendous importance in the context of subclavian vein cannulation, implanted venous access portals, and supraclavicular nerve block for regional anaesthesia.
Adult
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Brachial Plexus
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abnormalities
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Cadaver
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Dissection
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Humans
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Male
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Phrenic Nerve
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abnormalities
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Singapore
3.Twin reverse arterial perfusion sequence.
N A Z Nik LAH ; C A Che YAAKOB ; M S OTHMAN ; N M Z Nik MAHMOOD
Singapore medical journal 2007;48(12):e335-7
Twin reverse arterial perfusion sequence occurs in approximately one percent of monochorionic twins. This condition is always fatal for the recipient twin and carries a high mortality rate for the pump twin. Various treatment options are described, but management is continually evolving with the publication of new data. We report an acardiac acephalic monochorionic twin who was diagnosed at 31 weeks gestation. Serial ultrasonographical examinations of the normal pump twin showed intrauterine growth restriction but with no evidence of heart failure. A healthy pump twin was delivered by caesarean section at 34 weeks.
Abnormalities, Multiple
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diagnostic imaging
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Cesarean Section
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Female
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Fetofetal Transfusion
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diagnostic imaging
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Follow-Up Studies
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Gestational Age
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Heart Defects, Congenital
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diagnostic imaging
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Humans
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Infant, Newborn
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Pregnancy
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Pregnancy Outcome
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Pregnancy Reduction, Multifetal
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methods
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Pregnancy, Multiple
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Twins, Monozygotic
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Ultrasonography, Prenatal
4.The bi-directional link between women's and men's mental health.
Singapore medical journal 2007;48(10):971-972
Female
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Humans
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Male
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Men's Health
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Mental Health
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Spouse Abuse
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prevention & control
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Spouses
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psychology
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Women's Health
6.Red cell autoantibodies among thalassaemia patients in Hospital Universiti Sains Malaysia.
M N Noor HASLINA ; N ARIFFIN ; I Illuni HAYATI ; H ROSLINE
Singapore medical journal 2007;48(10):922-925
INTRODUCTIONThalassaemia is one of the major public health problems in Malaysia. Regular monthly blood transfusion remains the main treatment for severe thalassaemia patients. One of the complications of blood transfusion is the formation by the recipients of alloantibodies and autoantibodies against red blood cell (RBC) antigen. The purpose of this study was to determine the prevalence of RBC autoantibodies among multiple-transfused thalassaemic patients in our institution and factors that contribute to its development.
METHODSA prospective study was conducted in Haematology Laboratory, Hospital Universiti Sains Malaysia between January 2004 and December 2004. A total of 63 thalassaemia patients, who received regular blood transfusion were included in this study. Clinical and serological data were collected and analysed prospectively. Blood samples were subjected to standard blood bank procedures for screening of antibodies and their subsequent identification using reagent of Diamed-ID Gel microtyping system.
RESULTSThere were 49 (77.8 percent) patients with Hb E/beta-thalassaemia, ten (15.9 percent) beta-thalassaemia major, three (4.7 percent) Hb H Constant Spring and one (1.6 percent) Hb H disease. Only one (1.6 percent) patient had autoantibodies. There were no statistical associations found between the formation of autoantibodies with age at the start of transfusion, number of packed cell transfused and splenectomy.
CONCLUSIONOur data showed a low autoimmunisation rate in multiple-transfused thalassaemia patients in our hospital.
Adolescent ; Adult ; Autoantibodies ; blood ; Blood Group Antigens ; immunology ; Child ; Child, Preschool ; Coombs Test ; Erythrocytes ; immunology ; Female ; Hospitals, University ; Humans ; Malaysia ; Male ; Middle Aged ; Prospective Studies ; Thalassemia ; blood ; Transfusion Reaction
7.Lamotrigine in pregnancy: safety profile and the risk of malformations.
Prakash ; L V PRABHU ; M A NASAR ; R RAI ; S MADHYASTHA ; G SINGH
Singapore medical journal 2007;48(10):880-883
The use of antiepileptic drugs in pregnancy always presents challenges to doctors and their patients as it may have deleterious effects on the developing embryo. Lamotrigine is most commonly-prescribed drug among the newer antiepileptic drugs; hence, it has been selected for the present review. A number of studies pertaining to the safety of lamotrigine use during pregnancy have been reported, with differing results. Contradictory results have been reported in animals regarding lamotrigine teratogenicity, and human studies have also proven inconclusive. In many countries, human pregnancy registries are maintained to establish the safety of antiepileptic drugs during pregnancy, as all the different suggestions favour some over others, with specific antiepileptic combinations still being questioned. It is our hope that the present work may integrate the available disparate relevant facts into a directed effort towards minimising the risk of foetal compromise.
Abnormalities, Drug-Induced
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Animals
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Anticonvulsants
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adverse effects
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therapeutic use
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Epilepsy
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drug therapy
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Female
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Folic Acid Deficiency
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chemically induced
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Humans
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Pregnancy
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Teratogens
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pharmacokinetics
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pharmacology
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Triazines
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adverse effects
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therapeutic use
8.The use of midazolam and haloperidol in cancer patients at the end of life.
L K Radha KRISHNA ; V J POULOSE ; C GOH
Singapore medical journal 2012;53(1):62-66
INTRODUCTIONThis study aimed to describe the patterns of sedative use among terminally ill cancer patients who were referred to a hospital-based specialist palliative care service for symptom management. It also aimed to examine whether sedative use among terminally ill cancer patients during the last two days of life had any impact on their survival.
METHODSA retrospective review of case notes was carried out for patients with a diagnosis of terminal cancer, who died in a 95-bedded oncology ward between September 2006 and September 2007. Data was collected on patient characteristics, duration of palliative care, indications and doses of sedatives used at 48 hours and 24 hours before death.
RESULTSA total of 238 patients died while receiving specialist palliative care, 132 of whom (55.5%) were female. At 48 hours and 24 hours before death, 22.6% and 24.8% of patients, respectively, were on sedatives like midazolam, haloperidol or both. The median dose of midazolam was 5 mg/day while the haloperidol dose at 48 hours and 24 hours before death was 3 mg/day and 4 mg/day, respectively. The indications for midazolam were anxiety, breathlessness and stiffness, while those for haloperidol were confusion agitation and nausea. Survival analysis showed no significant difference in survival between patients who were on sedatives and those who were not. The p-value for log-rank test was 0.78.
CONCLUSIONThe results showed that the doses and overall frequency of sedative use in this patient population tended to be low and that usage of sedatives had no deleterious influence on survival.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Analgesics, Opioid ; therapeutic use ; Female ; Haloperidol ; therapeutic use ; Humans ; Hypnotics and Sedatives ; therapeutic use ; Male ; Midazolam ; therapeutic use ; Middle Aged ; Neoplasms ; drug therapy ; mortality ; Palliative Care ; methods ; Retrospective Studies ; Terminal Care ; methods ; Terminally Ill ; Time Factors ; Treatment Outcome
10.Effect of 11β-HSD1 dehydrogenase activity on bone histomorphometry of glucocorticoid-induced osteoporotic male Sprague-Dawley rats.
M R Elvy SUHANA ; H S FARIHAH ; O FAIZAH ; A S NAZRUN ; M NORAZLINA ; M NORLIZA ; S IMA-NIRWANA
Singapore medical journal 2011;52(11):786-793
INTRODUCTIONGlucocorticoids cause osteoporosis by decreasing bone formation and increasing bone resorption activity. Glucocorticoid action in bones depends on the activity of 11-beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme, which plays an important role in regulating corticosteroids. 11β-HSD1 is expressed by human and rat osteoblasts. We aimed to investigate the relationship between 11β-HSD1 dehydrogenase activity and bone histomorphometric changes in glucocorticoid-induced osteoporotic bone in rats.
METHODSA total of 30 male Sprague-Dawley rats (aged three months, weighing 200-250 g) were divided into three groups of ten each. Group 1 rats were the baseline control, which were sacrificed untreated at the beginning of the study. Group 2 rats underwent sham operation and were administered with vehicle olive oil intramuscularly at 0.05 ml/kg. Group 3 rats were adrenalectomised and administered with an intramuscular injection of dexamethasone 120 μg/kg body weight/day. The treatment was started two weeks after the operation, for a duration of two months. Plasma osteocalcin, plasma pyrodinoline, plasma corticosterone and 11β-HSD1 were measured, and bone histomorphometry analysis was performed.
RESULTSDexamethasone treatment caused an increase in plasma corticosterone level, together with a significant reduction in 11β-HSD1 dehydrogenase activity of the bone, along with a higher plasma level of the bone resorption marker, pyridinoline. Dexamethasone treatment also caused a reduction in trabecular volume, number and thickness, and an increase in trabecular separation.
CONCLUSIONLong-term glucocorticoid treatment reduces the 11β-HSD1 dehydrogenase activity in the bone, which can otherwise lead to bone loss due to the increased level of active glucocorticoids.
11-beta-Hydroxysteroid Dehydrogenase Type 1 ; metabolism ; Adrenal Cortex Hormones ; metabolism ; Amino Acids ; pharmacology ; Animals ; Body Weight ; Bone and Bones ; metabolism ; Corticosterone ; blood ; Dexamethasone ; pharmacology ; Enzyme-Linked Immunosorbent Assay ; methods ; Gene Expression Regulation, Enzymologic ; Glucocorticoids ; metabolism ; Humans ; Male ; Osteoporosis ; metabolism ; Rats ; Rats, Sprague-Dawley