Comparison of Ki-67 antigen expression and K-ras mutation in lung tumours induced by urethane in mice

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Singapore Med J 2009; 50(7): 729-733
Comparison of Ki-67 antigen expression and K-ras mutation in lung tumours induced by urethane in mice

Koohdani F, Sasani F, Mohammad K, Mehdipour P
Correspondence: Dr Fariba Koohdani, fkoohdan@sina.tums.ac.ir

ABSTRACT
Introduction
This study aims to compare Ki-67 antigen expression and K-ras mutation in lung tumours induced by the interfering effects of urethane followed by sodium nitrite, sodium chloride and vitamin D3.
Methods The samples were classified into six groups: control (C) group; urethane only (U) group; urethane and vitamin D (U+D) group which received 3.5 mg/kg vitamin D3 for four weeks; urethane and sodium nitrite (U+NS) group which was given sodium nitrite (50mg/L); urethane and physiological serum (U+NaCl) group; and sodium nitrite and physiological serum (NS+NaCl) group which was given 50 mg/L sodium nitrite and physiological serum, instead of water. The four carcinogen groups receiving urethane were injected intraperitoneally with 600 mg/kg of urethane three times. After 20 weeks of intervention, the mice were killed; the tissues were removed and examined for histopathological changes and comparison of Ki-67 antigen expression and mutations in the exon 1 of the K-ras gene in lung tumours.
Results There were significant differences in the Ki-67 index between the C group and the U (p-value is less than 0.006, 95 percent confidence interval [CI] -432.9 to -55.6), U+D (p-value is less than 0.05, 95 percent CI -408.3 to -4.6), U+NS (p-value less than 0.02, 95 percent CI -415.7 to -27.2), U+NaCl (p-value less than 0.002, 95 percent CI -478.8 to -90.3) groups. There was no difference between the C and NS+NaC1 groups. There was no mutation in the exon 1 of K-ras gene of the lung tumours.
Conclusion The expression of Ki-67 antigen was found to be increased by urethane in the present study. However, a study on a larger sample size may show anti-tumourogenic effect of vitamin D3. However, the K-ras exon 1 mutations do not play any role in the interfering effects of urethane followed by sodium nitrite and sodium chloride.

Keywords: carcinogens, K-ras genes, Ki-67 antigen, lung tumour, vitamin D, urethane
Singapore Med J 2009; 50(7): 729-733

Incidence of thyroid malignancy among goitrous thyroid lesions from the Sarawak General Hospital 2000-2004

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Singapore Med J 2009; 50(7): 724-728
Incidence of thyroid malignancy among goitrous thyroid lesions from the Sarawak General Hospital 2000-2004

Htwe TT, Hamdi MM, Swethadri GK, Wong JOL, Soe MM, Abdullah MS
Correspondence: Dr Than Than Htwe, lavenderhtwe@yahoo.com

ABSTRACT
Introduction
Thyroid cancer is the most common among all endocrine malignancies. The worldwide prevalence of goitre in the general population is estimated at 4–7 percent and the incidence of malignancy in goitrous thyroid is about ten percent. It is postulated that goitrous thyroid is a precursor lesion to the development of malignant thyroid diseases. As Sarawak is a state well known for endemic goitre, this study focused on establishing the incidence of thyroid malignancy among goitrous thyroid swellings.
Methods This study was a hospital-based retrospective study on the archived collection of the surgically-removed thyroid specimens from the Sarawak General Hospital, Malaysia. Cases were grouped into cancer and non-cancer groups. The cancer group included papillary thyroid carcinoma (PTC), PTC follicular variant, follicular carcinoma and anaplastic carcinoma (ANA).
Results A total of 820 thyroid cases which underwent surgical removal in years 2000 to 2004 were collected. Of these, 143 (17.4 percent) were male and 677 (82.6 percent) female. It was observed that the highest prevalence of thyroid swelling cases occurred in the age group 41–60 years while the lowest prevalence occurred in the age group under 21 years, 371 (45.2 percent) vs. 31 (3.8 percent). By ethnicity, the Ibans and Malays were found to have a higher prevalence at 275 (33.5 percent) and 196 (23.9 percent), respectively, while the lowest prevalence was observed in Indians, 11 (1.3 percent). 55 cases (6.7 percent) were found to be cancerous and the rest (93.3 percent) were non-cancerous thyroid swellings. Histologically, the highest incidence of carcinoma was PTC (4.0 percent) and the lowest was ANA (0.2 percent).
Conclusion Based on our observations, although goitrous thyroid swelling is quite a common problem in Sarawak, thyroid malignancy is not a major issue. Among thyroid malignancies, PTC is the most common histological type of malignancy.

Keywords: goitre, papillary thyroid carcinoma, thyroid cancer, thyroid malignancy
Singapore Med J 2009; 50(7): 724-728

A profile of cancer patient outcomes from a tertiary care teaching hospital in Malaysia

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Singapore Med J 2009; 50(7): 720-723
A profile of cancer patient outcomes from a tertiary care teaching hospital in Malaysia

Suthahar A, Gurpreet K, Ambigga D, Maniam T, Dhachayani S, Fuad I, Adlina S
Correspondence: Dr Suthahar Ariaratnam, suthahar@salam.uitm.edu.my

ABSTRACT
Introduction
The aim of this paper was to determine the sociodemographic and cancer characteristics of patients with cancer at a tertiary care centre.
Methods For the study, 80 newly-diagnosed cancer patients were selected and interviewed using structured questionnaires that included sociodemographic and cancer characteristic profiles. At the end of the study period of two years, the survivorship status of the patients was determined.
Results Gender, occupational status, type of cancer and stage of cancer were found to be significantly associated with the survival status among the study group of cancer patients. Results of logistic regression analysis showed that deceased patients were significantly more likely to be pensioners rather than employed, aged 60–69 years rather than 40–49 years, to have all other types of cancer rather than breast cancer, and to be in Stage 3 or 4 of the disease rather than in Stage 1 of the disease.
Conclusion There is a greater necessity for psychosocial research in order to achieve optimal health for patients with cancer, and in turn, to improve the survival of cancer patients.

Keywords: cancer characteristics, cancer profile, sociodemographic profile, survivorship status, tertiary care
Singapore Med J 2009; 50(7): 720-723

Some interesting observations on the surface features of the liver and their clinical implications

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Singapore Med J 2009; 50(7): 715-719
Some interesting observations on the surface features of the liver and their clinical implications

Joshi SD, Joshi SS, Athavale SA
Correspondence: Dr Subhash D Joshi, sdjoshi_2003@hotmail.com

ABSTRACT
Introduction
A sound knowledge of the normal and variant liver anatomy is a prerequisite to having a favourable surgical outcome. Knowledge of the commonly-occurring variations assumes even more significance in the era of diagnostic imaging and minimally-invasive surgical approaches. Although the segmental anatomy of the liver has been extensively researched, very few studies have dealt with the surface variations of the liver.
Methods 90 formalin-fixed livers were utilised for the study. Variations regarding the shapes of the caudate and the quadrate lobes as well as the normal fissures were observed. The presence of the accessory fissures and any other variations on the surface of the livers were noted.
Results Varied shapes of the caudate and the quadrate lobes were encountered. Notching along the inferior border of the caudate lobe was seen in 18 percent of livers, a vertical fissure was observed in 30 percent, and prominent papillary process was seen in 32 percent. Accessory fissures and grooves were more common in the right lobe. Multiple prominent vertical grooves were observed on the anterosuperior surface of the liver in six percent of livers. Quadrate lobe was absent in four percent, and in two cases, it was found to be deeply buried. Presence of a pons hepatis, bridging the left and the quadrate lobes, was observed in 30 percent of the livers examined.
Conclusion Our study is expected to serve as a guide for proper interpretations of liver images using various imaging modalities. It will also be useful to the operating surgeons to be aware of the frequently-occurring morphological variations on the liver surface.

Keywords: accessory fissures, caudate lobe, liver anatomy, papillary process, pons hepatis, quadrate lobe
Singapore Med J 2009; 50(7): 715-719

Utility of abdominal ultrasonography in HIV patients

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Singapore Med J 2009; 50(7): 710-714
Utility of abdominal ultrasonography in HIV patients

Chakraborty PP, Bandyopadhyay D
Correspondence: Dr Partha Pratim Chakraborty, docparthapc@yahoo.co.in

ABSTRACT
Introduction
Various diseases associated with human immunodeficiency virus (HIV) infection are often difficult to diagnose. A poor immune response, atypical presentations and opportunistic pathologies all contribute to this difficulty. We tried to evaluate the utility of routine abdominal ultrasonography (US) in new and follow-up HIV cases, and compared the results among those with a clinical need for US and those where US was performed as a routine screening.
Methods 150 consecutive seropositive patients were subdivided into four groups depending on the necessity of abdominal US on the initial workup, i.e. Group A (38 patients) or B (112 patients), and whether they were newly-diagnosed HIV patients or follow-up patients, i.e. Group X (62 patients) or Y (88 patients), giving us subgroups, AX (22 patients), AY (16 patients), BX (40 patients) and BY (72 patients).
Results The prevalence of significant US findings was higher in those with CD4 less than 200 cells/ml (77.8 percent) compared to those with CD4 200–500 cells/ml and CD4 more than 500 cells/ml (65.5 percent and 37 percent, respectively). 24 out of 38 patients with clinical indications and 71 out of 112 patients without any obvious clinical need for US, had positive findings on US, the majority of which had a major therapeutic impact.
Conclusion We conclude that abdominal US is a simple and cost-effective tool in resource-poor countries like India, where HIV care is becoming more and more important.

Keywords: acquired immunodeficiency syndrome, active anti-retroviral therapy, anti-retroviral therapy, highly hepatic venous thrombosis, highly-active anti-retroviral therapy, human immunodeficiency virus, ultrasonography
Singapore Med J 2009; 50(7): 710-714

The usefulness of early ultrasonography, electroencephalography and clinical parameters in predicting adverse outcomes in asphyxiated term infants

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Singapore Med J 2009; 50(7): 705-709
The usefulness of early ultrasonography, electroencephalography and clinical parameters in predicting adverse outcomes in asphyxiated term infants

Ong LC, Kanaheswari Y, Chandran V, Rohana J, Yong SC, Boo NY
Correspondence: Prof Ong Lai Choo, onglc@ppukm.ukm.my

ABSTRACT
Introduction
The early identification of asphyxiated infants at high risk of adverse outcomes and the early selection of those who might benefit from neuroprotective therapies are required. A prospective observational study was conducted to determine if there were any early clinical, neuroimaging or neurophysiological parameters that might predict the outcome in term newborns with asphyxia.
Methods 44 term newborns with acute asphyxia had a cranial ultrasonography (US), electroencephalography (EEG) and clinical examination performed between three and eight hours of life to determine the parameters that might predict outcome. US findings were classified as normal or abnormal (ventricular dilatation or compression and/or focal/diffuse echogenicities). EEG background activity was classified into two categories:normal/mildly abnormal/intermediate, or severely abnormal (low voltage activity or “suppression-burst”). An intrapartum score (based on graded abnormalities of foetal heart monitoring, umbilical arterial base deficit and five-minute Apgar score) and a hypoxic ischaemic encephalopathy (HIE) score (based on graded abnormalities of the neurological and respiratory status at 3–8 hours of life) was also obtained.
Results At one year of life, eight infants had died, six had defaulted follow-up, five had major impairment, two minor impairment and 23 were normal. On univariate analysis, poor outcome (death or major impairment) was associated with abnormal cranial US, severely abnormal EEG and a high HIE score (greater than or equal to 15). The positive predictive value was 54.5, 100 and 100 percent, respectively, while the negative predictive value was 93.8, 80.6 and 80.6 percent, respectively. Combining these factors did not improve the predictive values.
Conclusion There was no added advantage in combining EEG or US parameters over a clinical neurological scoring system alone in predicting the outcome of asphyxiated term newborns.

Keywords: asphyxia, cranial ultrasonography, electroencephalography, neonatal asphyxia, newborn
Singapore Med J 2009; 50(7): 705-709

Palmar pressure distribution during push-up exercise

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Singapore Med J 2009; 50(7): 702-704
Palmar pressure distribution during push-up exercise

Chuckpaiwong B, Harnroongroj T
Correspondence: Dr Bavornrit Chuckpaiwong, chuck003@gmail.com

ABSTRACT
Introduction
Doing repetitive push-ups is among the most common exercise for the upper body and shoulder stabiliser muscle strength training. However, adverse effects such as neck pain, back pain, palmar pain and wrist pain have been reported. To date, to our knowledge, palmar pressure when performing push-ups has not been previously reported. We hypothesised that various hand positions during push-ups may provide different palmar pressures.
Methods Bilateral palmar pressures were recorded in ten individual volunteers. All the subjects were set up for doing push-ups in five positions of the hand. Peak palmar pressure was recorded by Emed pressure platform system (Novel GmBH, Munich, Germany). The palm was divided into the following five anatomic regions, viz. thenar, lunate, hypothenar, metacarpals and fingers. Statistical comparison between the five positions of the hand was analysed using the analysis of variance test.
Results A distribution of the mean peak pressure of the lunate and hypothenar areas were relatively higher than the other areas in both standby and full-elbow flexion positions. At the palmar position 30 cm wider than the shoulder width, the palmar pressure revealed significantly higher peak pressure in the lunate area in the standby and fully-flexed elbow positions (p-value is less than 0.05). At the palmar position 10 cm narrower than the shoulder width, palmar pressure showed significantly higher peak pressure in the hypothenar area only in the fully-flexed elbow position.
Conclusion The information regarding palmar pressures while performing push-ups in different hand positions may be used as a guideline for exercise modification, especially in injured athletes.

Keywords: exercise complication, palmar pain, palmar pressure, push-up exercise, sports injury, wrist pain
Singapore Med J 2009; 50(7): 702-704

Erectile dysfunction as a sentinel marker of endothelial dysfunction disease

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Singapore Med J 2009; 50(7): 698-701
Erectile dysfunction as a sentinel marker of endothelial dysfunction disease

Lojanapiwat B, Weerusawin T, Kuanprasert S
Correspondence: Dr Lojanapiwat Bannakij, blojanap@mail.med.cmu.ac.th

ABSTRACT
Introduction
Vascular disease is the major underlying cause of erectile dysfunction (ED). Endothelial dysfunction acts as a marker of “peripheral vascular disease” that occurs prior to clinical vascular disease. ED is the first clinical manifestation of endothelial disease due to the small size of the penile artery. Brachial flow-mediated vasodilation (FMD) is one of the accurate tests for evaluating endothelial function. We compared the endothelial function by FMD between ED patients without clinical signs of vascular disease and non-ED patients.
Methods 41 ED patients and 30 age-matched normal control subjects were assessed for cardiovascular risks and endothelial function. We measured the FMD in order to evaluate the endothelial function, by comparing the percentage change of the brachial arterial diameter after the brachial arterial occlusion.
Results There were no significant differences in baseline characteristics, cardiovascular risks and lipid values between both groups, except that the high-density lipoprotein cholesterol was higher in the control group. The percentage change of the FMD was 8.7 +/- 1.0 percent and 5.1 +/- 0.6 percent in ED patients and control subjects, respectively (p-value is 0.007).
Conclusion ED is the first clinical presentation of sub-clinical endothelial dysfunction disease prior to the appearance of clinical cardiovascular disease or cardiovascular risk factors. ED can be the sentinel marker of early cardiovascular and other systemic vascular diseases and it should thus be employed in preventive strategies.

Keywords: brachial flow-mediated vasodilation, cardiovascular disease, endothelial dysfunction disease, erectile dysfunction, sentinel marker
Singapore Med J 2009; 50(7): 698-701

B-Lynch suture for the treatment of uterine atony

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Singapore Med J 2009; 50(7): 693-697
B-Lynch suture for the treatment of uterine atony

Koh E, Devendra K, Tan LK
Correspondence: Dr Elisa Koh, elisakoh@gmail.com

ABSTRACT
Introduction
Over 125,000 women die of postpartum haemorrhage (PPH) each year, with the commonest cause being uterine atony (75–90 percent). Failing conservative management, hysterectomy is usually the final resort. In 1997, Christopher B-Lynch devised an innovative technique to treat uterine atony, and it has been widely used around the world since its original report. However, there are hardly any reports of this technique being utilised in East Asian countries, including Singapore. Our study reviews the cases in which the B-Lynch suture was used to treat uterine atony, and the clinical outcomes of these cases.
Methods A retrospective study of data of all women who delivered between May 2004 and June 2007 was collected from the department’s database, to identify patients who had undergone the B-Lynch procedure. Primary PPH is defined as a blood loss of more than 500 ml at or within 24 hours of delivery.
Results There were a total of 5,470 deliveries during this period, with primary PPH occurring in 100 cases. The B-Lynch procedure was performed in seven women, avoiding the need for a hysterectomy in five cases.
Conclusion Our series of cases treated with the B-Lynch procedure showed that it is an effective method of containing PPH. It has the advantage of being applied easily and rapidly, and should be taught to all trainees and registrars in obstetrics. It should be attempted when conservative management of PPH fails and before any radical surgery is considered.

Keywords: B-Lynch suture, hysterectomy, postpartum haemorrhage, uterine atony
Singapore Med J 2009; 50(7): 693-697

Retention rates of disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis

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Singapore Med J 2009; 50(7): 686-692
Retention rates of disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis

Agarwal S, Zaman T, Handa R
Correspondence: Dr Rohini Handa, rohinihanda@hotmail.com

ABSTRACT
Introduction
Disease-modifying anti-rheumatic drugs (DMARDs) currently form the mainstay of treatment of rheumatoid arthritis (RA). We aimed to evaluate the retention rates of “therapeutic segments” of DMARDs in patients with RA.
Methods This was a cross-sectional study of RA patients with at least one year of follow-up. A therapeutic segment is said to begin when one DMARD combination is instituted and it ends with a subsequent change. The disability index for each patient was calculated using a modified health assessment questionnaire. Retention rates were calculated using the Kaplan Meier survival analysis.
Results 375 DMARD courses in 102 patients were analysed. 99 courses were being continued at the time of the study and hence were censored for the purposes of analysis. The respective median (interquartile range [IQR]) retention period for segments containing methotrexate (MTX), sulfasalazine, hydroxychloroquine and leflunomide was 28 (15–45), 12 (3–20), 18 (9–24), 15 (4–32) months. The log-rank statistical test indicated that MTX was retained longer singly (median [IQR] 43 [32–70] months) than in combination (median [IQR] 19 [10–24] months) (p-value is 0.001). The commonest reason for the discontinuation of the DMARD segment was the disease “slipping out” of control (51.1 percent) followed by adverse effects (24.3 percent). Treatment termination on account of disease control was encountered in 16.3 percent of courses only. As many as 63 percent of single DMARD segments were changed because of disease “slip out” as compared to 41 percent of combination DMARD segments. Adverse effects were a more frequent cause of termination of the combination segments (32 vs. 15 percent).
Conclusion MTX, used singly, had the highest retention rates among all the DMARDs used in RA patients. Disease “slip out” and adverse effects frequently required a change of the therapeutic segment.

Keywords: disease-modifying anti-rheumatic drugs, methotrexate, retention rate, rheumatoid arthritis, therapeutic segment
Singapore Med J 2009; 50(7): 686-692