Learning Curve for Flow Diversion of Posterior Circulation Aneurysms: A Long-Term International Multicenter Cohort Study.

BACKGROUND AND PURPOSE: Flow diversion has gradually become a standard treatment for intracranial aneurysms of the anterior circulation. Recently, the off-label use of the flow diverters to treat posterior circulation aneurysms has also increased despite initial concerns of rupture and the suboptimal results. This study aimed to explore the change in complication rates and treatment outcomes across time for posterior circulation aneurysms treated using flow diversion and to further evaluate the mechanisms and variables that could potentially explain the change and outcomes. MATERIALS AND METHODS: A retrospective review using a standardized data set at multiple international academic institutions was performed to identify patients with ruptured and unruptured posterior circulation aneurysms treated with flow diversion during a decade spanning January 2011 to January 2020. This period was then categorized into 4 intervals. RESULTS: A total of 378 procedures were performed during the study period. Across time, there was an increasing tendency to treat more vertebral artery and fewer large vertebrobasilar aneurysms (P = .05). Moreover, interventionalists have been increasingly using fewer overlapping flow diverters per aneurysm (P = .07). There was a trend toward a decrease in the rate of thromboembolic complications from 15.8% in 2011-13 to 8.9% in 2018-19 (P = .34). CONCLUSIONS: This multicenter experience revealed a trend toward treating fewer basilar aneurysms, smaller aneurysms, and increased usage of a single flow diverter, leading to a decrease in the rate of thromboembolic and hemorrhagic complications.

Risk of Branch Occlusion and Ischemic Complications with the Pipeline Embolization Device in the Treatment of Posterior Circulation Aneurysms.

BACKGROUND AND PURPOSE: Flow diversion with the Pipeline Embolization Device is increasingly used for endovascular treatment of intracranial aneurysms due to high reported obliteration rates and low associated morbidity. While obliteration of covered branches in the anterior circulation is generally asymptomatic, this has not been studied within the posterior circulation. The aim of this study was to evaluate the association between branch coverage and occlusion, as well as associated ischemic events in a cohort of patients with posterior circulation aneurysms treated with the Pipeline Embolization Device. MATERIALS AND METHODS: A retrospective review of prospectively maintained databases at 8 academic institutions from 2009 to 2016 was performed to identify patients with posterior circulation aneurysms treated with the Pipeline Embolization Device. Branch coverage following placement was evaluated, including the posterior inferior cerebellar artery, anterior inferior cerebellar artery, superior cerebellar artery, and posterior cerebral artery. If the Pipeline Embolization Device crossed the ostia of the contralateral vertebral artery, its long-term patency was assessed as well. RESULTS: A cohort of 129 consecutive patients underwent treatment of 131 posterior circulation aneurysms with the Pipeline Embolization Device. Adjunctive coiling was used in 40 (31.0%) procedures. One or more branches were covered in 103 (79.8%) procedures. At a median follow-up of 11 months, 11% were occluded, most frequently the vertebral artery (34.8%). Branch obliteration was most common among asymptomatic aneurysms (P < .001). Ischemic complications occurred in 29 (22.5%) procedures. On multivariable analysis, there was no significant difference in ischemic complications in cases in which a branch was covered (P = .24) or occluded (P = .16). CONCLUSIONS: There was a low occlusion incidence in end arteries following branch coverage at last follow-up. The incidence was higher in the posterior cerebral artery and vertebral artery where collateral supply is high. Branch occlusion was not associated with a significant increase in ischemic complications.

Predictors of Incomplete Occlusion following Pipeline Embolization of Intracranial Aneurysms: Is It Less Effective in Older Patients?

BACKGROUND AND PURPOSE: Flow diversion with the Pipeline Embolization Device (PED) for the treatment of intracranial aneurysms is associated with a high rate of aneurysm occlusion. However, clinical and radiographic predictors of incomplete aneurysm occlusion are poorly defined. In this study, predictors of incomplete occlusion at last angiographic follow-up after PED treatment were assessed. MATERIALS AND METHODS: A retrospective analysis of consecutive aneurysms treated with the PED between 2009 and 2016, at 3 academic institutions in the United States, was performed. Cases with angiographic follow-up were selected to evaluate factors predictive of incomplete aneurysm occlusion at last follow-up. RESULTS: We identified 465 aneurysms treated with the PED; 380 (81.7%) aneurysms (329 procedures; median age, 58 years; female/male ratio, 4.8:1) had angiographic follow-up, and were included. Complete occlusion (100%) was achieved in 78.2% of aneurysms. Near-complete (90%-99%) and partial (<90%) occlusion were collectively achieved in 21.8% of aneurysms and defined as incomplete occlusion. Of aneurysms followed for at least 12 months (211 of 380), complete occlusion was achieved in 83.9%. Older age (older than 70 years), nonsmoking status, aneurysm location within the posterior communicating artery or posterior circulation, greater aneurysm maximal diameter (≥21 mm), and shorter follow-up time (<12 months) were significantly associated with incomplete aneurysm occlusion at last angiographic follow-up on univariable analysis. However, on multivariable logistic regression, only age, smoking status, and duration of follow-up were independently associated with occlusion status. CONCLUSIONS: Complete occlusion following PED treatment of intracranial aneurysms can be influenced by several factors related to the patient, aneurysm, and treatment. Of these factors, older age (older than 70 years) and nonsmoking status were independent predictors of incomplete occlusion. While the physiologic explanation for these findings remains unknown, identification of factors predictive of incomplete aneurysm occlusion following PED placement can assist in patient selection and counseling and might provide insight into the biologic factors affecting endothelialization.

Treatment of Tandem Internal Carotid Artery Aneurysms Using a Single Pipeline Embolization Device: Evaluation of Safety and Efficacy.

BACKGROUND AND PURPOSE: Tandem aneurysms are defined as multiple aneurysms located in close proximity on the same parent vessel. Endovascular treatment of these aneurysms has rarely been reported. Our aim was to evaluate the safety and efficacy of a single Pipeline Embolization Device for the treatment of tandem aneurysms of the internal carotid artery. MATERIALS AND METHODS: A retrospective analysis of consecutive aneurysms treated with the Pipeline Embolization Device between 2009 and 2016 at 3 institutions in the United States was performed. Cases included aneurysms of the ICA treated with a single Pipeline Embolization Device, and they were divided into tandem versus solitary. Angiographic and clinical outcomes were compared. RESULTS: The solitary group (median age, 58 years) underwent 184 Pipeline Embolization Device procedures for 184 aneurysms. The tandem group (median age, 50.5 years) underwent 34 procedures for 78 aneurysms. Aneurysms were primarily located along the paraophthalmic segment of the ICA in both the single and tandem groups (72.3% versus 78.2%, respectively, P = .53). The median maximal diameters in the solitary and tandem groups were 6.2 and 6.7 mm, respectively. Complete occlusion on the last angiographic follow-up was achieved in 75.1% of aneurysms in the single compared with 88.6%% in the tandem group (P = .06). Symptomatic thromboembolic complications were encountered in 2.7% and 8.8% of procedures in the single and tandem groups, respectively (P = .08). CONCLUSIONS: Tandem aneurysms of the ICA can be treated with a single Pipeline Embolization Device with high rates of complete occlusion. While there appeared to be a trend toward higher thromboembolic complication rates, this did not reach statistical significance.

Collar Sign in Incompletely Occluded Aneurysms after Pipeline Embolization: Evaluation with Angiography and Optical Coherence Tomography.

BACKGROUND AND PURPOSE: Flow diversion with the Pipeline Embolization Device has emerged as an attractive treatment for cerebral aneurysms. Processes involved in aneurysm occlusion include changes in intra-aneurysmal hemodynamics and endothelialization of the device. Here, we call attention to a radiographic sign not previously reported that is detected in incompletely occluded aneurysms after treatment with the Pipeline Embolization Device at angiographic follow-up and referred to as the "collar sign." MATERIALS AND METHODS: A retrospective review of all patients who underwent placement of a Pipeline Embolization Device for cerebral aneurysms between January 2014 and May 2016 was performed. All aneurysms found to show the collar sign at follow-up were included. Optical coherence tomography was performed in 1 case. RESULTS: One hundred thirty-five aneurysms were treated in 115 patients. At angiographic follow-up, 17 (10.7%) aneurysms were found to be incompletely occluded. Ten (58.8%) of these aneurysms (average diameter, 7.9 ± 5.0 mm) were found to have the collar sign at angiographic follow-up (average, 5.5 ± 1.0 months). Four (40.0%) of the aneurysms underwent a second angiographic follow-up (average, 11.0 ± 0.9 months) after treatment, and again were incompletely occluded and showing the collar sign. Two patients underwent retreatment with a second Pipeline Embolization Device. Optical coherence tomography showed great variability of endothelialization at the proximal end of the Pipeline Embolization Device. CONCLUSIONS: The collar sign appears to be indicative of endothelialization, but continued blood flow into the aneurysm. This is unusual given the processes involved in aneurysm occlusion after placement of the Pipeline Embolization Device and has not been previously reported.

The fallopian canal: a comprehensive review and proposal of a new classification.

INTRODUCTION: The facial nerve follows a complex course through the skull base. Understanding its anatomy is crucial during standard skull base approaches and resection of certain skull base tumors closely related to the nerve, especially, tumors at the cerebellopontine angle. METHODS: Herein, we review the fallopian canal and its implications in surgical approaches to the skull base. Furthermore, we suggest a new classification. CONCLUSIONS: Based on the anatomy and literature, we propose that the meatal segment of the facial nerve be included as a component of the fallopian canal. A comprehensive knowledge of the course of the facial nerve is important to those who treat patients with pathology of or near this cranial nerve.

The ventricular system of the brain: a comprehensive review of its history, anatomy, histology, embryology, and surgical considerations.

INTRODUCTION: The cerebral ventricles have been recognized since ancient medical history. Their true function started to be realized more than a thousand years later. Their anatomy and function are extremely important in the neurosurgical panorama. METHODS: The literature was searched for articles and textbooks of different topics related to the history, anatomy, physiology, histology, embryology and surgical considerations of the brain ventricles. CONCLUSION: Herein, we summarize the literature about the cerebral ventricular system.

Gabriele Fallopio (1523-1562) and his contributions to the development of medicine and anatomy.

INTRODUCTION: Gabriele Fallopio was one of the greatest anatomists of the sixteenth century. He discovered and named numerous parts of the human body. His name survives to this day as it is associated with several anatomical structures including the Fallopian canal, Fallopian hiatus, Fallopian valve, Fallopian muscle, and the Fallopian tube. CONCLUSIONS: Our current knowledge of human anatomy is based on giants such as Fallopio. His contributions to neuroanatomy laid the foundations for the development of this discipline.

Prevalence of human papillomavirus in abnormal cervical smears in Malaysian patients.

Cervical cancer is the second most common female malignancy in Malaysia. Despite advances in treatment, the overall survival for this disease has not changed in the last decade. Infection by certain types of HPV is recognized as a causal and necessary factor for its development. This study was carried out to determine the prevalence of HPV infection in abnormal cervical smears in Malaysian patients using archival cervical smears retrieved from the Cytopathology Unit, Universiti Kebangsaan Malaysia Medical Centre (UKMMC) between the years 1992-1995. DNA was extracted from 38 abnormal smears comprising 25 intraepithelial lesions and 13 cervical carcinomas and 10 normal smears. Amplification of HPV genes was carried out using the polymerase chain reaction (PCR) technique. HPV genotypes were determined using direct sequencing and the results were compared to the database from Genebank. DNA was successfully extracted from all 48 cervical smears. High-risk HPV (HR-HPV) genotypes were detected in 95% of the abnormal smears. Eight high-risk oncogenic types were identified: 16, 18, 31, 51, 52, 56, 58 and 66. All (100%) cervical cancer smears showed presence of HR-HPV compared to 92% of the cervical intraepithelial lesions. Among the eight HR-HPV genotypes identified, HPV 16 and 52 were the commonest (23.7% each) HPV genotypes encountered and among the CIN lesions, HPV 16 (28%) was the most frequent. We conclude that HPV 16 is the most prevalent HPV genotype present in abnormal cervical smears in Malaysian patients, and that the use of archival material to assess the presence of HPV is potentially worthwhile, and can be utilized for longitudinal studies of HPV presence and persistence.

Diet, nutritional knowledge and health status of urban middle-aged Malaysian women.

The objective of the study was to assess nutritional and health status as well as nutritional knowledge in urban middle-aged Malaysian women. The impact of menopause on diet and health indices was also studied. The study included 360 disease free women, non users of HRT,aged > or =45 years with an intact uterus recruited from November 1999 to October 2001. Personal characteristics, anthropometric measurements and blood sample were acquired followed by clinical examination. Nutrient intake and nutritional knowledge was determined by a quantitative FFQ and KAP. The findings showed that urban middle-aged women, aged 51.65+/-5.40 years had energy intakes (EI) 11% below RDA, consisting of 53% carbohydrates, 15% protein and a 32% fat which declined with age. The sample which comprised of 42.5% postmenopausal women had a satisfactory diet and healthy lifestyle practices. Premenopausal women consumed more dietary fat (6%) with other aspects of diet comparable to the postmenopausal women. Iron intake was deficient in premenopausal women, amounting to 56% RDA contributing to a 26% prevalence of anaemia. Overall, calcium intake reached 440 mg daily but dairy products were not the main source. The postmenopaused had a more artherogenic lipid profile with significantly higher total cholesterol (TC) and LDL-C, but more premenopausal women were overweight/obese (49% versus 35%). EI was the strongest predictor for BMI and waist circumference (WC), with WC itself an independent predictor of fasting blood sugar and TC with BMI strongly affecting glucose tolerance. High nutritional knowledge was seen in 39% whereas 20% had poor knowledge. Newspapers and magazines, followed by the subject's social circle, were the main sources of nutritional information. Nutritional knowledge was positively associated with education, household income, vitamin/ mineral supplementation and regular physical activity but inversely related to TC. In conclusion, middle-aged urban women had an adequate diet with low iron and calcium intakes. Nutritional knowledge was positively associated to healthier lifestyle practices and lower TC. A comparable nutrient intake and lifestyle between pre and postmenopausal women suggested that health changes associated with menopause was largely independent of diet.

The effect of a machined collar on coronal hard tissue around titanium implants: a radiographic study in the canine mandible.

PURPOSE: The purpose of this study was to radiographically evaluate the effect of a machined titanium coronal collar on the marginal bone around 1-part endosseous dental implants placed at different heights relative to the bone crest. MATERIALS AND METHODS: Sixty dental implants were placed in edentulous spaces bilaterally in 5 foxhounds. Thirty test implants had a sandblasted, large-grit, dual acid-etched surface (SLA) over the entire length of the implant. The other 30 implants (control) had a machined collar around the most coronal 1.8 mm of the implant; an SLA surface covered the remainder of the implant. Both control and test implants were placed at 3 distinct levels relative to the bone crest. Six implants (3 control and 3 test) were randomly placed side by side in each hemimandible. Radiographs were taken at placement (baseline) and monthly for 6 months postplacement using a standardized radiographic template. RESULTS: Fifty-eight of the implants integrated and were analyzed on each proximal surface. Bone loss occurred around all implants over the 6 months of the study. In general, implants placed with the top of the SLA surface above the bone crest had significantly less bone loss than implants with the top of the SLA surface placed flush with the bone level. Apically placed implants had greater bone loss than coronally placed implants. The magnitude of bone loss around paired control and test implants was approximately the same. DISCUSSION AND CONCLUSION: The least bone loss with each implant type was observed when the top of the implant was placed above the alveolar crest. When there was no machined collar, the least distance from the implant top to the bone crest (not, however, the least bone loss) was observed when the top of the implant was level with the bone crest.

Bone health in urban midlife Malaysian women: risk factors and prevention.

The aim of this study was to identify risk factors associated with osteoporosis in urban midlife Malaysian women and to assess the effectiveness of lifestyle intervention in bone loss prevention with hormone replacement therapy (HRT) as a positive control. A total of 514 disease-free, uterus-intact, non-HRT-using women aged 45 years and older were recruited into the study. After initial bone mineral density (BMD) assessments, they were randomized into three groups: GI (control), G2 (lifestyle intervention), and G3 (lifestyle intervention with HRT). The study group was composed of 67.5% Chinese, 27.8% Malay, and 4.2% Indians with a mean age of 51.07+/-5.28 years. Two-fifths were postmenopausal, and the prevalence of osteoporosis was 24.1%, seen predominantly at the hip. Postmenopausal women had significantly lower mean BMD and a higher incidence of osteoporosis compared with the premenopausal women, 42.1% vs. 11.1% (p<0.0005). A lower incidence of osteoporosis was found in women who took calcium supplementation regularly as opposed to those who do not, 18.7% vs. 29.3% (p=0.036). Age and a greater postmenopausal duration showed a significant negative association with BMD, whereas higher family income, weight, body mass index, and waist and hip circumference were positively correlated. After 18-20 months, the effect of intervention was assessed based on BMD values of 279 women at baseline and after intervention. Lifestyle intervention alone was effective in premenopausal women, preventing over 90% of spinal bone loss compared with the controls, who lost 11.6% (0.046 g/cm2) bone mass with similar losses of hip bone, 2.0% (0.026 g/cm2) vs. 1.5% (0.020 g/cm2). Premenopausal women on HRT also showed a substantial decrease in spine and hip BMD, 18.6% (0.081 g/cm2) and 9.0% (0.122 g/cm2), respectively. The lifestyle intervention program retarded postmenopausal bone loss by 21% and 37% compared with controls, who lost 9.6% (0.141 g/cm2) and 6.0% (0.138 g/cm2) bone mass at the spine and hip. In comparison, lifestyle intervention with HRT increased postmenopausal BMD by 12.7% (0.216 g/cm2) at the spine and 1.9% (0.042 g/cm2) at the hip. The changes in hip BMD were influenced by current age, ethnicity, and income, while intervention had the strongest effect on spine BMD changes. In conclusion, lifestyle intervention prevented spinal bone loss in premenopausal women and retarded postmenopausal spine and hip bone loss compared with controls. The benefits of physical activity on spine and hip BMD highlight its potential as a safe and cost-effective alternative to HRT, which is not advocated because of its potential adverse effects.

Nitric oxide synthase activity in blood vessels of spontaneously hypertensive rats: antioxidant protection by gamma-tocotrienol.

Involvement of free radicals and nitric oxide (NO) has long been implicated to the pathogenesis of essential hypertension. Several studies using antioxidants as the radical scavenger have shown to confer protection against free radical mediated diseases. This study is designed to investigate the role of antioxidant gamma-tocotrienol on endothelial nitric oxide synthase (NOS) activity in spontaneously hypertensive rats (SHR). SHR's were divided into four groups namely untreated SHR (HC), treatment with 15 mg gamma-tocotrienol/kg diet (gammal), 30 mg gamma-tocotrienol/kg diet (gamma2) and 150 mg gamma-tocotrienol/kg diet (gamma3) and studied for three months. Wister Kyoto (WKY) rats were used as the control (C). Blood pressure was recorded every fortnightly by tail plethysmography. Animals were sacrificed and NOS activity in blood vessels was measured by [3H]arginine radioactive assay. Nitrite concentration in plasma was determined by Greis assay and lipid peroxides in the blood vessels by spectrofluorometry. This study showed that gamma-tocotrienol significantly reduced systolic blood pressure (SBP) in SHRs with a maximum reduction in group treated with gamma-tocotrienol 15 mg/kg diet (HC: 210 +/- 9 mmHg, gammal:123 +/- 19 mmHg). Blood vessels from untreated SHR showed a reduced NOS activity compare to that of WKY rats (C: 1.54 +/- 0.26 pmol/mg protein, HC: 0.87 +/- 0.23 pmol/mg protein; p<0.001). Gamma-tocotrienol improves NOS activity in all the groups with more significance in group gamma2 (p<0.001) and gamma3 (p<0.05). Plasma level of nitrite was reduced in SHR from 55 +/- 3 microM/ml in WKY to 26+/-2 muM/ml (p<0.001). Plasma nitrite level was reversed by treatment with gamma-tocotrienol. (gammal: p<0.001, gamma2: p<0.005, gamma3: p<0.001, respectively). In all the treatment groups, NOS activity showed significant negative correlation with blood pressure (gammal: r=-0.716, p<0.05; gamma2: r=-0.709, p<0.05; gamma3: r=-0.789, p<0.05). For plasma nitrite, although it shows a negative correlation with blood pressure it was significant only in gammal (r=-0.676, p<0.05) and gamma2 (r=-0.721, p<0.05). From this study we found that compared to WKY rats, SHR has lower NOS activity in blood vessels, which upon treatment with antioxidant gamma-tocotrienol increased the NO activity and concomitantly reduced the blood pressure. These findings further strengthen the hypothesis that free radicals and NO play critical role in pathogenesis of essential hypertension.

CT guided pararectal seed implant for localized prostate cancer: a preliminary report.

One hundred and fifty-two patients were treated with CT guided pararectal prostate seed implant (CPSI) alone or in combination with external-beam 3D conformal radiation therapy (EB3DRT) and Androgen Blockage Hormone Therapy (HT). A decrease and normalization in PSA values was seen following treatment in all groups. However, a better therapeutic response was observed in the individuals that received CPSI and EB3DRT with hormone therapy.

Ambulatory surgery and anaesthesia in HUKM, a teaching hospital in Malaysia: the first two years experience.

Ambulatory or day care surgery is still in its infancy in this part of the world. Our newly built university affiliated hospital started its Day Surgery Centre in February 1998. It is the first multidisciplinary ambulatory surgery centre in a teaching hospital in the country. It caters for Orthopaedic surgery, Urology, Plastic surgery, Otorhinolaryngology, General surgery, Paediatric surgery and Ophthalmology. We have done 2,604 cases and our unanticipated admission rate is less than 2%. There has been no major morbidity or mortality. The problems of setting up a multidisciplinary ambulatory centre in a teaching hospital are discussed.

Congenital hypothyroid screening using cord blood TSH.

BACKGROUND: Clinical diagnosis of congenital hypothyroidism (CH) is difficult at birth without neonatal screening. In line with the priorities of the national health services in Malaysia towards preventive medicine, early diagnosis and treatment of CH is emphasised. We conducted a pilot study at Kuala Lumpur's Maternity Hospital between April 1995 and November 1995 to estimate the incidence of CH and also evaluated the problems associated with large-scale neonatal screening using a commercial TSH kit on cord bloodspots. PATIENTS: A total of 11,000 newborns were screened using cord blood spots taken at birth. RESULTS: Two hundred and fifty newborns (2.27%) hand cord TSH > 20 mlU/L and had to be recalled for re-evaluation. Of these, 4 had cord TSH of > 100 mlU/L; three were confirmed to have congenital hypothyroidism and one had transient hyperthyrotropinaemia. Our study estimated the incidence of CH to be one in 3,666 live births in Kuala Lumpur, Malaysia. Clinical features of hypothyroidism are subtle during the early weeks of life. However, prolonged neonatal jaundice (3/3), widely opened posterior fontanelle (3/3) and dry skin (3/3) were the common features in all our cases by 2-6 weeks of life. CONCLUSION: This study suffered a high dropout rate. Twenty-six percent of the patients were not traceable after discharge and 48% did not respond to our recall. We stress the importance of public education and awareness in contributing to the cost-effectiveness of the screening program.

Assessing the status of intrauterine insemination before forming a medically assisted conception unit.

A survey in 1996 of our female patients suggest that the three commonest causes of infertility were endometriosis, anovulation and idiopathic which comprises of about 70% of all the patients. In the male patients, sperm morphology evaluation by critical criteria showed that abnormal morphology was present in 71% while 87% of all the semen analysis were abnormal. The objective of this study was to assess the status of IUI before proceeding to formulate patient protocols for IVF in a tertiary infertility referral unit. A retrospective study of patients data was done from Jan 1995 to Dec 1996. Ovarian stimulation by clomiphene for anovulatory and idiopathic patients was performed on couples with at least one patent fallopian tube. Ovulation induction was by an intramuscular injection of 5000 i.u of HCG after follicular maturation. IUI was performed approximately 36-40 hours later. A total of 74 couples received 114 treatment cycles producing a total of 9 conceptions. The conception rate of IUI was therefore 7.89% per cycle and 12.16% per couple with the cumulative pregnancy rate of 28.21%. Associated success features of IUI found in this study were the age of the woman and the semen parameters of the husband.

A successful pregnancy outcome in treated vulval rhabdomyosarcoma.

A 14 year old girl presented in 1986 with a huge perineal swelling which was progressively increasing in size and associated with loss of weight and loss of appetite. Biopsy from the mass revealed rhabdomyosarcoma of the vulva. She was treated with chemotherapy and radium implant. She responded well to the regime. Fibrosis of the vulva and vagina caused difficulty in consummation. Once it was corrected, she conceived easily and proceeded to a normal pregnancy and delivery.

Detection of xanthine oxidase in human plasma.

Xanthine oxidase is a highly versatile enzyme which is widely distributed among various species. Though the presence of the enzyme in serum is not yet established, high antibody titre of this enzyme has been reported. Xanthine oxidase is thought to be the principal source of free radical generation via degradation of nucleotides to the end product, uric acid. The aim of this study was to detect xanthine oxidase activity in human plasma and report any significant relationships found between its activity and variables such as race, age and sex for the sample size studied. Forty six normal healthy individuals (14 males and 32 females) were studied. The enzyme activity was measured by a spectrophotometric method whereby the reduction of ferricytochrome c by free radicals was calculated and expressed as nmol O2 production/ml/min. Results obtained showed that there was a positive relationship between xanthine oxidase activity with age (r = 0.415, p < 0.05) and weight (r = 0.369, p < 0.05) in the normal individual. For the age group 30-39 yrs (n = 11), a higher enzyme activity was observed in males (2.71 +/- 1.44) as compared to females (2.34 +/- 1.23) but it was not significant (p = 0.53). For racial distribution, the Malays [M] have a higher enzyme activity (2.65 +/- 0.86, N = 32) than their Indian [I] (2.27 +/- 0.58; N = 7) and Chinese counterparts [C] (1.44 +/- 1.22; N = 7) but this was also not statistically significant (M vs I: p = 0.39; M vs C: p = 0.07; I vs C: p = 0.16). In conclusion this study showed that there is a measurable amount of xanthine oxidase activity in the human plasma.

Uric acid, xanthine oxidase and other risk factors of hypertension in normotensive subjects.

Uric acid produced by xanthine oxidase (also a source of superoxide radicals) has been known to increase in hypertensive patients. In this study we evaluated the possible involvement of uric acid and xanthine oxidase in the pathogenesis of hypertension by examining their association with mean arterial pressure (MAP) and factors related to blood pressure. These factors include age, quetelet index (weight/height2), cholesterol, creatinine, calcium (Ca), magnesium (Mg), sodium (Na), potassium (K) and urea. Fifty Two (male-19, female-33) normal healthy individuals were studied. Correlation studies of demographic variables showed that age was positively correlated with MAP [r = 0.309, p = 0.026] and cholesterol [r = 0.503, p = 0.000] while quetelet index was positively correlated with age [r = 422, p = 0.000] MAP [r = 0.331, p = 0.016] and xanthine oxidase [r = 0.331, p = 0.016]. MAP was positively correlated with uric acid [r = 0.511, p = 0.000], cholesterol [r = 0.492, p = 0.000] and xanthine oxidase enzyme activity [r = 0.388, p = 0.004] and negatively correlated with plasma calcium [r = 0.603, p = 0.000]. Correlation studies of measured parameters with uric acid and xanthine oxidase showed that uric acid was positively correlated with creatinine [r = 0.627, p = 0.000], plasma magnesium [r 0.442, p = 0.001] and negatively correlated with plasma calcium [r = 0.546, p = 0.000] while xanthine oxidase was negatively correlated with plasma calcium [r = -0.404, p = 0.003] and plasma sodium [r = -0.288, p = 0.038]. Stepwise multiple regression with MAP as dependent variable showed that 65% of total variability of blood pressure can be accounted for by plasma calcium, cholesterol, creatinine, plasma K, plasma Na, uric acid and xanthine oxidase in order of increasing R2 [xanthine oxidase: T-value = 3.26, R2 = 0.653]. It can be concluded that in normotensive subjects, uric acid and xanthine oxidase have significant association with blood pressure and thus are one of the many factors which are involved in the cause or effect of hypertension.