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Biomedical subjects

P Y Ng

Publications and source records attributed to P Y Ng.

At least 19 recordsLinked to original sources

MRI findings in osmotic myelinolysis.

OBJECTIVES: Osmotic myelinolysis is a distinctive clinical syndrome with characteristic CT and MR features. This study was undertaken to determine the MR appearance of these lesions on T1 and T2-weighted, and diffusion-weighted imaging (DWI) sequences with apparent diffusion coefficient (ADC) mapping. MATERIALS AND METHODS: We describe six patients who presented with deranged serum sodium levels and subsequently developed osmotic myelinolysis. CT and MRI scans were retrospectively reviewed, including the advanced functional MR sequence of DWI with ADC mapping. RESULTS: Both cerebral white matter and pontine lesions were typically hypo and hyper-intense on T1 and T2W sequences respectively. Lesions were mildly hyperintense on isotropic DWI images with elevation of the ADC. CONCLUSION: MRI is superior to CT in depicting lesions in osmotic myelinolysis. DWI with ADC mapping suggests that osmotic myelinolysis is not simply a demyelinating disorder but has similarities to multiple sclerosis.

Adult↗

Biological evaluation of hepatitis C virus helicase inhibitors.

A small chemical library has been synthesized and assayed for inhibition of HCV helicase activity. This study provides the structure-activity relationship of the reported inhibitors, with emphasis placed on the aminophenylbenzimidazole moiety and the linkers. Our data highlight the importance of preserving the aminophenylbenzimidazole core and the hydrophobic linkers for biological activity. The development of a robust HCV helicase assay is also described.

Benzimidazoles↗

Hypertensive basal ganglia hemorrhage: a prospective study comparing surgical and nonsurgical management.

BACKGROUND: The optimal treatment of hypertensive supratentorial intracerebral hemorrhage is still debated. Some studies have shown no improvement in survival or functional outcome after surgery when compared to conservative management while others have shown otherwise. METHODS: This study was a prospective trial, matching patients for hematoma volume and Glasgow Coma score on admission. RESULTS: There were a total of 34 patients. Seventeen were treated conservatively and 17 surgically. There was no significant difference between the two groups in terms of age, GCS, hematoma volume, or presence of intraventricular blood. At 3, 6, and 12-month follow-up, they were assessed using the Modified Barthel Index by a blinded observer. There was no difference between the two groups at 3, 6, or 12 months follow-up. The mortality rate was similar in the two groups. CONCLUSIONS: Based on this study and review of the literature, we cannot recommend routine evacuation of clots to treat these hemorrhages.

Adult↗

Expression of endothelial cell angiogenesis receptors in human cerebrovascular malformations.

OBJECTIVE: To further understand the role of angiogenic growth factors in the development of cerebral cavernous malformations (CCMs) and arteriovenous malformations (AVMs), we investigated endothelial cell (EC) expression of receptors for vascular endothelial growth factor (VEGF) and angiopoietin systems in patients with surgically resected lesions. METHODS: Paraffin-embedded sections of five AVMs, CCMs, and normal control brain tissue samples were stained immunohistochemically with antibodies to von Willebrand factor and CD31 (to characterize ECs) and angiogenesis growth factor receptors Flt-1 (VEGF-R1), Flk-1 (VEGF-R2), Tie-1, and Tie-2. We counted large and small vessels in each specimen, assessed each specimen's immunoexpression of each antigen, and analyzed differences between CCMs, AVMs, and the normal control brain tissue samples. RESULTS: The ECs of CCMs, AVMs, and normal control brain tissue samples expressed the von Willebrand factor uniformly, but the ECs of CCMs were largely negative for CD31 (P < 0.05). Flk-1, Flt-1, and Tie-2 were not expressed in the control brain tissue samples. The proportion of immunopositive vessels to VEGF receptors Flk-1 and Flt-1 was significantly greater in AVMs and CCMs than in the control brain tissue samples (P < 0.05). Tie-2 in AVMs and CCMs was expressed in a higher percentage of immunopositive vessels than in the control brain tissue samples, but the difference was not statistically significant. Tie-1 was expressed in rare vessels of all lesion types and control brain tissue samples. CONCLUSION: ECs of CCMs do not seem to express CD31 to the same extent that AVMs and normal brain tissue do. AVMs and CCMs show greater expression of VEGF receptors, but not of angiopoietin receptors, than normal brain tissue does.

Adolescent↗

Nitric oxide and subarachnoid hemorrhage: elevated level in cerebrospinal fluid and their implications.

OBJECTIVE: Nitric oxide (NO) plays an important role in the pathogenesis of neuronal injury after brain ischemia, and decreased levels of NO have been implicated in the pathogenesis of vasospasm after subarachnoid hemorrhage (SAH). In this study, we measured the ventricular cerebrospinal fluid (CSF) NO levels in patients with SAH and correlated the levels with clinical grade and middle cerebral artery velocities measured with transcranial Doppler ultrasound. METHODS: All patients with spontaneous SAH documented on computed tomography and with an external ventricular drain inserted within 24 hours of hemorrhage were included in the study. A total of 16 patients were studied between August 1999 and August 2000. CSF was collected serially at the time of surgery and subsequently at daily intervals. It was collected during the time that the external ventricular drain remained patent and in situ. NO levels were measured by photometric analysis by using a nitrite/nitrate assay kit (Cayman Chemical, Ann Arbor, MI). RESULTS: The peak NO level in patients with SAH ranged from 9.96 to 168.16 micromol, with a median of 36.93 micromol. The levels were significantly elevated as compared with the control group (5.16 micromol, P < 0.05). The median NO level in patients with poor-grade SAH was 67.14 micromol as compared with 27.42 micromol in patients with good-grade hemorrhage (P < 0.05). No correlation was seen between CSF NO levels and middle cerebral artery velocities. The median NO level was 33.2 micromol in patients with a poor outcome as compared with 30.25 micromol in patients with a good outcome (P > 0.05). CONCLUSION: This study showed that NO levels are elevated after spontaneous SAH, and the degree of elevation is higher in patients with poor-grade SAH.

Adult↗

Neuroprotection in acute stroke.

PURPOSE: To highlight recent advances in neuroprotection in acute stroke. DATA SOURCES: A MEDLINE search was conducted from January 1985 to November 2000. Key words included neuroprotection, cerebrovascular, subarachnoid haemorrhage, perioperative stroke, hypothermia and apopotosis. All articles in English were considered for review. Additional articles were identified from the references of the retrieved articles and cross-referencing selected articles. DATA EXTRACTION: All clinical studies and review articles and abstracts were reviewed. DATA SYNTHESIS: The neuronal cells of the central nervous system are susceptible to various forms of insult such as ischaemia and haemorrhage. Each step along the ischaemic cascade is a potential target for therapeutic intervention. Neuroprotective agents are designed to minimise cellular injury and salvage brain tissue. In cerebral ischaemia, only thrombolysis had been shown to improve clinical outcome. Neuroprotective therapy has definite benefits in animals but not in humans. It may potentially extend the time window for thrombolysis. In aneurysmal subarachnoid haemorrhage, the only agent with proven efficacy is nimodipine. Research is ongoing in the development of new drugs. Currently several phase III trials are in progress. CONCLUSION: There is substantial optimism in the development of neuroprotective therapy to improve outcome in stroke patients.

Humans↗

Advances in neurointensive care.

PURPOSE: To highlight recent advances in neurological and neurosurgical intensive care. DATA SOURCES: A MEDLINE search was conducted from January 1980 to August 2000. Keywords included intensive care, head injury, subarachnoid haemorrhage, status epilepticus, myasthenic crisis, Guillain-Barre syndrome and stroke. All articles in English were considered for review. Additional articles were identified from the references of the retrieved articles and cross-referencing selected articles. DATA EXTRACTION: All clinical studies, review articles and abstracts were reviewed. DATA SYNTHESIS: Rapid advances in neurological and neurosurgical intensive care in the last decade have led to the development of specialised neurointensive care units with joint ventures between neurology and neurosurgery. Work in these units have contributed immensely to our understanding of the pathophysiology and management of acute brain injury. The principles of intensive care management include amelioration or reversal of brain injury and preservation of normal neural tissue. Treatment algorithms are possible with the aid of intense clinical and neurophysiologic monitoring. Ongoing clinical and basic science research may provide new treatment options for the intensivist in the acute phase of brain injury. CONCLUSION: Specialised neurointensive care units provide the best environment for the patient with acute brain injury. Outcome is frequently enhanced the clinicians skilled towards dealing with the whole spectrum of neurologic insults.

Critical Care↗

Prostatic neoplasia in transgenic mice with prostate-directed overexpression of the c-myc oncoprotein.

BACKGROUND: Promoter elements within the 5' DNA region of the rat C(3)1 gene have been shown to direct prostate-specific expression of gene products when they are fused through recombinant DNA procedures and used to produce transgenic mice. In order to test the in vivo effects of chronic overexpression of the mouse c-myc protooncogene on the prostate glands of transgenic mice, we created several lines of C(3)1-c-myc transgenic mice and then examined the phenotype of males with this genetic alteration. METHODS: The modified promoter and 5' region of the rat C(3)1 gene was fused to the coding region of the mouse c-myc gene using recombinant DNA techniques. This DNA was used to create three different founder lines of transgenic mice. Tissues from males and females heterozygous for the transgene were examined for expression of the recombinant mouse c-myc mRNA by an RNase protection assay. Prostates from males were examined for expression of recombinant c-myc mRNA by in situ hybridization. Thin sections of fixed ventral prostates from males were analyzed by microscopy for histological abnormalities. RESULTS: Three different lines of transgenic mice were obtained from these procedures. These mice demonstrated expression of recombinant mouse c-myc mRNA in the testis and ventral prostates of males and in the uterus of females. In situ hybridization demonstrated that the epithelial cells were the source of recombinant c-myc expression in the ventral prostates of the transgenic lines. Microscopic analysis of the ventral prostates from these mice demonstrated abnormalities in epithelial cell morphology seemingly typical of an intraepithelial neoplasia-like phenotype. However, none of the males of any of the lines developed overt prostatic adenocarcinoma over their lifetimes. CONCLUSIONS: Chronic overexpression of c-myc in the ventral prostate epithelial cells of C3(1)-c-myc transgenic mice leads to the development of epithelial cell abnormalities similar to those seen in low-grade prostatic intraepithelial neoplasia in humans. These abnormalities were not found to progress to adenocarcinoma over the lifetimes of the transgenic mice, suggesting the need for additional oncogenic changes in the pathway to prostatic adenocarcinomas. Furthermore, our cumulative experience with the use of the C3(1) gene promoter in the generation of transgenic mice suggests that the probasin promoter element provides a much more specific and effective means to target transgenes to the prostate glands of mice.

Animals↗

Petrosal approach for a large right posterior cerebral artery (P2) aneurysm.

A seven year old girl presented with recurrent headaches Computed tomography (CT) magnetic resonance imaging (MRI) and angiography showed a 2 cm aneurysm at the P2 segment of the right posterior cerebral artery. The aneurysm was trapped successfully by a petrosal approach. The patient made an excellent recovery except for a transient fourth nerve palsy.

Child↗

Apoptosis occurs after cerebral contusions in humans.

OBJECTIVE: Animal model systems have shown that head trauma can induce cell death in regions of the brain away from the site of the impact via a process of apoptosis. We sought to determine whether there was evidence of cellular apoptosis in clinically collected materials from human head trauma patients, as well as to attempt to determine the pathway by which it may occur. METHODS: Thirty-one sequential specimens of brain tissue excised during emergency craniotomy for evacuation of cerebral contusions with mass effect were examined. Non-necrotic pericontusional tissues were detected in 11 samples. These were examined for the presence of apoptotic cells by the terminal deoxynucleotide transferase-mediated nick end labeling method as well as by immunohistochemistry to detect possible expression of the apoptosis-related genes p53, bcl-2, and bax. RESULTS: Bax expression was detected in all patients, whereas bcl-2 expression was noted in six patients. Terminal deoxynucleotide transferase-mediated nick end labeling-positive cells were noted in eight patients. One instance of p53-positive immunostaining was observed. Patients with bcl-2 expression had a better survival rate than patients in whom no bcl-2 expression was noted (P = 0.01). CONCLUSION: Although necrosis seemed to be the main finding in cerebral contusions, these results support the hypothesis that apoptosis does occur in patients after traumatic brain injury, and this may contribute to the secondary injury processes that are seen with head injury. Patients in whom anti-apoptotic bcl-2 is induced seem to have a better prognosis. This may have important clinical significance in the development of bcl-2 homologs or bax inhibitors to prevent apoptosis.

Adult↗

Intraoperative endovascular treatment as an adjunct to microsurgical clipping of paraclinoid aneurysms.

OBJECT: The endovascular procedure can provide proximal control, suction decompression, and prompt intraoperative angiography during microsurgical clipping of aneurysms of the paraclinoid segment of the internal carotid artery (ICA). The authors assess the safety and feasibility of this method in 24 consecutive cases. METHODS: Frontotemporal craniotomy and radical pterionectomy were performed with the patient's head immobilized in a radiolucent frame while femoral artery catheterization was achieved. Before dural opening, a balloon catheter with a coaxial lumen was positioned and tested in the ICA, after which microsurgical exposure was completed, including intradural clinoid drilling and optic canal decompression. Trapping of the lesion was achieved by inflating the balloon and placing a temporary clip beyond the aneurysm neck. The catheter was gently aspirated to achieve suction decompression and to facilitate clip application. Intraoperative digital subtraction angiography was then performed. Twenty-two aneurysms were larger than 10 mm, and 11 of them were giant. Six patients presented with subarachnoid hemorrhage and nine with visual symptoms. Balloon occlusion and suction decompression were performed in 16 cases (67%), and proximal control alone in 1 case. Intraoperative angiography was performed in every case. Subsequent clip readjustment was necessary in seven cases, including three cases of residual aneurysm filling and four of ICA compromise. Complete aneurysm obliteration was achieved in 20 cases, and greater than 90% obliteration in 22. One major infarct likely related to catheter thromboembolism was found. There were no instances of visual deterioration or other complications attributable to the endovascular procedure. CONCLUSIONS: The endovascular method allows safe and reliable proximal control, suction decompression, and intraoperative angiography in microsurgical treatment of large paraclinoid aneurysms.

Aged↗

Reduction of endothelial and smooth muscle density in the corpora cavernosa of the streptozotocin induced diabetic rat.

PURPOSE: Erectile dysfunction is one of the most prevalent complications of diabetes in males. Because adequate vascular perfusion is needed for appropriate erectile tissue function a likely reason for the high incidence of this complication in diabetics is a pathological change associated with the disease in vascularization of erectile tissues. We investigate whether chronic diabetes may induce changes in vascularization of the corpora cavernosa using a computerized image analysis system to quantify changes in the smooth muscle and endothelial cell content of the corpora cavernosa of diabetic rats induced by streptozotocin 6 months previously, and compare these changes to those associated with aging. MATERIALS AND METHODS: We studied 3 groups of rats, including 10-week-old untreated controls, diabetic rats treated with streptozotocin for 6 months starting at age 10 weeks and 18-month-old rats (aged). Penile shafts from these groups were excised, fixed, sectioned and immunostained with anti-smooth muscle actin to identify smooth muscle cells and anti-CD31 to identify endothelial cells. Computerized image analysis was used to quantify the percent area within the corpora cavernosa occupied by smooth muscle cells or endothelial cells, and the data were compared among the groups. RESULTS: We identified a highly significant decrease in the percentage of smooth muscle and endothelial cells within the cavernosa areas of diabetic rats compared to control or aged rats. Mean cavernous smooth muscle cell content was 15.28 +/- 2.54% in control rats and 9.83 +/- 1.21% in diabetic rats (p = 0.0001). Likewise, cavernous endothelial cell content was 6.93 +/- 0.86% in the control group and 4.01 +/- 1.08% in the diabetic group (p = 0. 0001). However, no statistical difference of smooth muscle or endothelial cell content was found between control and aged rats. CONCLUSIONS: Using the streptozotocin treated rat as a model for diabetes, we showed that smooth muscle and endothelial cell density is significantly decreased in diabetic corpora cavernosa but not in normal aged rats. This observation is a further step toward the understanding of the pathomechanisms for diabetic related erectile dysfunction.

Animals↗

Distal anterior cerebral artery aneurysms: a clinical series.

Thirty patients with distal anterior cerebral artery (DACA) aneurysms were seen at the Royal Adelaide Hospital in the period 1970-1996. There were seven males (23%) and twenty three females (77%) with a mean age of 50 years. The average follow up was 5 years. Multiple aneurysms were present in seven cases (23%). The mean size of aneurysms was 5 mm. There were two post-traumatic aneurysms and one mycotic aneurysm. Out of the 30 cases, 19 presented with subarachnoid haemorrhage from ruptured DACA aneurysms. Eight (42%) of them were in good clinical grade (I or II). Operations were carried out in 25 (83%) patients. All five cases with unruptured aneurysms and the eight patients with good clinical grade had good recovery. In contrast, only six (55%) out of 11 patients with poor clinical grade had good outcome. The overall management mortality for the 19 cases with ruptured aneurysms was 16%. Postoperative complication occurred in two cases (8%), one patient developed deep vein thrombosis and seizures, the other patient had transient upper limb weakness. Although there is a definite trend towards better management outcome in the published series of DACA aneurysms over the years, there is still significant mortality and morbidity in the poor grade patients. Early surgery will prevent the deaths from rebleeding and may allow optimal management of vasospasm.

Adult↗

Abnormal prostate development in C3(1)-bcl-2 transgenic mice.

BACKGROUND: Recent hypotheses to explain the etiology of abnormal growth associated with prostate disease have invoked perturbations in the rate of apoptosis as an important contributor to the onset and progression of these diseases. For this reason, the apoptosis suppressing oncoprotein bcl-2 has come under scrutiny with regards to its role in prostate diseases. In order to evaluate the role of bcl-2 in human prostate disease and to develop an animal model to test anti-bcl-2 therapies, we generated transgenic mice in which bcl-2 expression is targeted to the mouse prostate gland. METHODS: Mouse embryos were microinjected with recombinant DNA constructed by fusing a modified rat C3(1) promotor element to cDNA encoding human bcl-2. Presence of the C3(1)-bcl-2 transgene in progeny was identified by Southern blot and polymerase chain reaction (PCR) analysis. RNase protection assays were used to analyze RNA from 15 organs of these mice. Western blot assays and immunohistochemical staining were used to confirm the tissue-specific protein expression of human bcl-2 and its cellular localization. RESULTS: Three lines of C3(1)-bcl-2 transgenic mice were established. Founder mice carried 2-20 copies of the transgene. Expression of human bcl-2 from the transgene was limited to the prostate gland and testis of males as well as the uterus of females. In the prostate gland, human bcl-2 protein was found only in prostatic epithelial cells. Microscopic analysis of prostate glands from individual males (three lines) showed that these glands were often abnormal, with increased accumulation of cells in the prostatic stroma as well as the epithelium. CONCLUSIONS: These transgenic mice appear to provide a novel animal model for studying neoplastic development of the prostate, with particular emphasis on the bcl-2 protein and the role of apoptosis regulation in such development.

Animals↗

Brain abscesses: review of 30 cases treated with surgery.

Thirty patients with brain abscesses who were treated at the Department of Neurosurgery, Tan Tock Seng Hospital, Singapore, during the period July 1989 to July 1993, were reviewed. There were seven females and 23 males with mean follow up duration of 19 months. The predisposing factors identified were otogenic infections in 10 cases (33%), paranasal sinus infection in 2 cases (7%) and congenital heart disease in 6 cases (20%). All cases underwent aspiration or excision of the abscess. Repeat operations were carried out if the abscess reaccumulated. A total of 49 aspirations and 16 excisions were performed. Twenty-five patients (84%) made a good recovery, three patients (10%) were moderately disabled, one patient (3%) was severely disabled and one patient (3%) died. There was no postoperative haemorrhage or wound infections. Two patients (7%) developed hydrocephalus and three (10%) had seizures postoperatively.

Adolescent↗

Extra-articular manifestations are uncommon in southern Chinese with rheumatoid arthritis.

Rheumatoid arthritis is characterized by both articular and extra-articular manifestations. Few studies have addressed the prevalence of extra-articular manifestations in non-Caucasoid races. We have studied 153 Southern Chinese patients with RA and found that such features are uncommon when compared with previous reports in Caucasoids. The only extra-articular manifestations were rheumatoid nodules which were present in 4.6%, and episcleritis and cutaneous vasculitis in 0.7% each. A further 12.4% had mild sicca symptoms. These findings were in direct contrast with the severity of articular disease as 73% of patients had erosive disease which was graded as severe in 37%. The reason for the low prevalence of extra-articular manifestations is not known but may be due, in part, to the rarity of the HLA-DR4 subtype, HLA-Dw4 in the Southern Chinese population.

Adult↗

Hormone-regulated apoptosis results from reentry of differentiated prostate cells onto a defective cell cycle.

Castration initiates extensive apoptosis of the secretory epithelial cells lining the ducts of the rat ventral prostate, resulting in the striking regression of this male sexual accessory tissue. We had previously described the paradox of finding similar cascades of gene activity (c-fos greater than c-myc greater than hsp-70) induced during the early period of ventral prostate regression and during the regrowth of the ventral prostate gland initiated by testosterone replenishment. This common pattern of protooncogene expression during periods of predominant cellular apoptosis or proliferation caused us to examine further the possibility that the two cellular events occur through identical early molecular pathways. In the present study we demonstrate that apoptotic prostate epithelial cells incorporate bromodeoxyuridine into nuclear high-molecular-weight DNA prior to nuclear DNA fragmentation. The DNA synthetic activity occurs in coordination with a massive induction of proliferative cell nuclear antigen, a proliferation marker, in the nuclei of androgen-deprived prostatic epithelial cells. Moreover, this activity is also associated with the increased expression of mRNA encoding p53, a suppressor gene well known as a cell cycle-blocking agent. Our data indicate that quiescent (G0) prostate epithelial cells undergo apoptosis due to two sequential events initiated by testosterone depletion. The first event is the active reentry of these cells into the cell cycle. The second event is the apoptotic destruction resulting from the inability of the differentiated cells to successfully complete this cycle.

Animals↗