Vasospasm and delayed cerebral ischaemia in patients with spontaneous subarachnoid haemorrhage (aneurysmal and pretruncal non-aneurysmal): a centre's perspective.

BACKGROUND: Spontaneous subarachnoid haemorrhage (SAH) is a significant cause of stroke and associated with high morbidity and mortality. One substantial complication of SAH is cerebral vasospasm (CV) and delayed cerebral ischemia (DCI). This study aimed to define the clinical profile in patients with SAH, CV and DCI secondary to spontaneous SAH (aneurysmal and pretruncal non-aneurysmal). MATERIALS AND METHODS: We analysed 122 consecutive patients with spontaneous SAH following intracranial aneurysmal and non-aneurysmal information (including patients' pattern characterisation and their possible risk factor association to pre-operative clinical decision and long-term clinical outcome) was documented and analysed. RESULTS: The main clinical presentations for spontaneous SAH following ruptured intracranial aneurysm and nonaneurysm were headache (77%) and nausea/vomiting (62.3%). The most common sites for SAH following ruptured intracranial aneurysm rupture were the anterior and posterior communicating arteries (57.5%). Hypertension was the most common cause for SAH at 64.8%. It was found 26.2% (n=32) out of the 122 patients developed CV and DCI. The mean day of vasospasm was 6.0 ± 2.8 (range: 1-14 days) Age, length of stay, nausea/vomiting and visual field defect were significantly associated (p<0.05) with vasospasm. Mortality rate was also higher in the CV group compared to the group without CV in both at discharge and at 6 months; 281 versus 278 per 1000 and 312 vs 300 per 1000, respectively. CONCLUSION: CV and DCI have a significant incidence among local patients with spontaneous SAH following an intracranial aneurysmal and non-aneurysmal rupture and it is associated with substantial morbidity. Prevention, effective monitoring, and early detection are keys to successful management. Regional investigation using a multicentre cohort to analyse mortality and survival rates may aid in improving national resource management of these patients.

Flow resistance analysis of extracranial-to-intracranial (EC-IC) vein bypass.

Although brain bypass surgery has often been selected to treat internal carotid arteries (ICA) which are restricted by aneurysm or artery stenosis, its effectiveness has not been quantitatively evaluated. The purpose of this study is to propose an innovative approach for the evaluation of brain extracranial-to-intracranial (EC-IC) vein bypass surgery, based on the analysis of flow resistance in vein bypasses and within their contralateral carotid arteries through the use of computational fluid dynamics (CFD). Seven patients who underwent vein bypass surgery were examined with the use of high-resolution; computed tomography angiogram (CTA). The reconstructed three-dimensional (3D) geometries were segmented to create CFD calculation domains. Colour Doppler ultrasound (CDU) was used to measure blood flow velocities at the common carotid arteries (CCA), in order to determine inflow conditions. Based on the pipe flow theory, pressure drop was expressed as Am²+Bm where A and B represent flow resistance coefficients and m represents blood mass flow rate. The CFD results revealed that for a healthy ICA, the average values of A and B were 0.013088 Pa/(ml/min)² and 3.105 Pa/(ml/min), respectively. For the vein bypass, an average value of A was 0.0143 Pa/(ml/min)² and B 3.402 Pa/(ml/min), which was approximately that of a healthy ICA. However, in the case of a bypass utilising a venous conduit possessing a large-sized valve or existing size alteration, the flow resistance in that bypass would be higher than those found in the healthy ICA. An imbalance of flow resistances may impose conditions that could predispose hemodynamic failure or distal aneurysm development.

Pneumocephalus: an uncommon finding in trauma.

Pneumocephalus (Intracranial aerocele), defined as intracranial air, is an uncommon complication in head injury patients. It can present immediately following head trauma or be delayed for many days before clinical symptoms occur. We present two cases of extensive pneumocephalus after trauma. The diagnosis was made by computed tomography (CT). When pneumocephalus is suspected, CT can play a vital role in determining the precise location of the gas collection, its relationship to the basal skull fracture site or air sinuses and the amount of mass effect on the brain.

Primary intracerebral haemorrhage in Malaysia: in-hospital mortality and outcome in patients from a hospital based registry.

Primary intracerebral haemorrhage (ICH) results in significant morbidity and mortality among patients. There is a paucity of epidemiological data on this condition in Malaysia. The purpose of this hospital based study was to define the clinical profile in patients with primary spontaneous intracerebral haemorrhage at University of Malaya Medical Centre (UMMC) and to determine the mortality rate of intracerebral haemorrhage at the time of discharge, the prognostic factors and one year outcome of this cohort of patients. Sixty-six patients were admitted at the Neurosurgical unit of University of Malaya Medical Centre for a period of 13 months from March 2002 to March 2003. Fifty percent of the subjects were female. The mean age was 61.6 +/- 16.7 years. Among our patients with intracerebral haemorrhage, the common risk factors were: hypertension (80.3%), diabetes mellitus (25.7%) and smoking (27.2%). Common presenting features for our series were: weakness (61.8%), LOC (58.5%), headache (56.3%) and speech disturbances (45.3%). On neuroimaging, the lesions were seen in basal ganglia/thalamus (45.1%), lobar (32.9%), brainstem (13.4%) and cerebelli (8.5%). The overall 30 days mortality rate for intracerebral haemorrhage (ICH) was 43.9%. The important predictors of for mortality were the GCS score on admission (p < 0.0001), haematoma volume > 30 mls (p < 0.0001), evidence of intraventricular extension (p = 0.011) and ICH score (p < 0.0001). At one year follow up, 48.5% (n = 32) were dead, 33.3% (n = 11) obtained good recovery, 36.4% (n = 12) moderate disability, 18.2% (n = 6) severe disability and 3% remain vegetative state. The overall mortality rate for our series of patients with primary intracerebral haemorrhage is quite similar to previously published epidemiological studies. ICH scoring is useful in the prognostication.

Patient-controlled analgesia with tramadol versus tramadol plus ketorolac.

AIM: In this double-blinded, randomized controlled trial, we compared the clinical advantages and disadvantages of patient-controlled-analgesia (PCA) with continuous infusion (CI) with tramadol alone versus a combination of tramadol plus ketorolac in the management of postoperative pain after major abdominal surgery. METHODS: Sixty adult patients were randomly assigned to 2 groups. Group T, was given 10 mg/mL tramadol and Group TK was given 1.50 mg/mL ketorolac plus 5 mg/mL tramadol. After an i.v. loading dose of 0.07 mL/kg, the demand bolus injection was set at 0.2 mL, with a lockout interval of 30 min, and a continuous background i.v. infusion was set at 1.5 mL/h. Data of PCA demand, dose delivered and total analgesic consumption were retrieved from the computer memory bank of PCA device. Visual analogue scale at rest, sedation score and the occurrence of adverse effects were assessed every 3 h for 18 h. RESULTS: No significant differences were found with regard to pain scores and side effects. Patients in Group TK were significantly more alert. CONCLUSIONS: We concluded that the combination of ketorolac plus tramadol in the same PCA device was an effective and safe treatment for postoperative analgesia in abdominal surgery.

Detection of differential expression of mouse interferon-alpha subtypes by polymerase chain reaction using specific primers.

Specific primers for nine mouse interferon-alpha (IFN-alpha) subtypes, namely, IFN-alpha1, IFN-alpha1-9, IFN-alpha2, IFN-alpha4, IFN-alpha5, IFN-alpha7, IFN-alpha6/8, IFN-alpha11, and IFN-alphaB, were designed and evaluated on Poly(I).Poly(C)-induced and influenza virus-infected L929 cells. Specificity of the primers was confirmed in a cross-polymerase chain reaction (cross-PCR). IFN-alpha1, IFN-alpha1-9, IFN-alpha4, IFN-alpha6/8, IFN-alpha11, and IFN-alphaB were found to be induced in L929 cells 6-9 h after Poly(I).Poly(C) treatment. The amplification of a particular subtype was not biased in the presence of excess of other templates. Differential expression of the IFN-alpha subtypes was observed in influenza A/NWS/33- and B/Lee/40-infected L929 cells. A/NWS/33 virus was found to upregulate the gene expression of IFN-alpha1, IFN-alpha4, IFN-alpha6/8, IFN-alpha11, and IFN-alphaB in L929 cells as early as 6 h after infection. In B/Lee/40-infected L929 cells, only IFN-alpha4 was upregulated. Our results suggest that the designed primers will serve as a useful tool in analyzing the expression of IFN-alpha subtypes in various systems and hence for the evaluation of their function.

Axillary brachial plexus block using peripheral nerve stimulator: a comparison between double- and triple-injection techniques.

BACKGROUND AND OBJECTIVES: The multiple-injection technique for axillary block, in which the main 4 nerves of the plexus are located by a nerve stimulator and separately injected, has been shown to produce a high success rate. However, this technique may prove to be more difficult and time-consuming than other methods. Therefore, a simplified technique, with a reduced number of injections, might be desirable. A comparison between 2- and 3-injection techniques was made in the present double-blind study. METHODS: One hundred patients were randomly allocated to 2 groups. In group 3N, the radial, median, and musculocutaneous nerves were located by a nerve stimulator and injections made. In group 2N, the radial and median nerves were located and injections made. Forty milliliters of local anesthetic was used. RESULTS: A greater success rate for anesthetizing the musculocutaneous nerve was found in group 3N (98% v 80%; P <.005). No differences between the groups were found in the success rate for blocking the radial, median, and ulnar nerves. The rate of complete block (all the sensory areas distal to the elbow) was 90% in group 3N and 76% in group 2N. The time to perform the block was shorter in group 2N (5 +/- 1 v 6 +/- 1 minutes; P <.001). CONCLUSIONS: The 2-injection technique offers a success rate in blocking the 3 nerves innervating the hand similar to that obtained with the 3-injection technique. The latter approach should be considered when the musculocutaneous nerve distribution is involved in the surgical area.

A designed protein with packing between left-handed and right-handed helices.

A common motif in protein structures is the assembly of alpha-helices. Natural alpha-helical assemblies, such as helical bundles and coiled coils, consist of multiple right-handed alpha-helices. Here we design a protein complex containing both left-handed and right-handed helices, with peptides of D- and L-amino acids, respectively. The two peptides, D-Acid and L-Base, feature hydrophobic heptad repeats and are designed to pack against each other in a "knobs-into-holes" manner. In solution, the peptides form a stable, helical heterotetramer with tight packing in the most solvent-protected core. This motif may be useful for designing protease-resistant, helical D-peptide ligands against biological protein targets.

Selective ulnar nerve localization is not essential for axillary brachial plexus block using a multiple nerve stimulation technique.

BACKGROUND AND OBJECTIVES: The multiple-injection technique for axillary block, in which the 4 distal nerves of the plexus are located by a nerve stimulator and separately injected, has been shown to produce a rapid onset and a high success rate. However, this technique may be more difficult and time consuming than other axillary block methods. A simplified multiple-nerve stimulation technique, in which the ulnar nerve was not located, was compared in the present double-blind study to the 4-injection approach. METHODS: Eighty-four patients were randomly allocated to 2 groups. In group IV, all 4 distal nerves of the plexus were located by a nerve stimulator and injections made. In group III, all the nerves but the ulnar were located and injections made. The block was defined as complete when analgesia was present in all the sensory areas distal to the elbow. RESULTS: The time to perform the block was shorter in group III (5 +/- 2 v 8 +/- 3 minutes; P <.001). Block performance pain was lower in group III patients (8 +/- 2 v 13 +/- 2 mm; P <.001). The onset time (15 +/- 6 v 16 +/- 7 minutes) and the frequency (90% v 92%) of complete block were not different between the groups. CONCLUSIONS: A triple-injection method of axillary block in which the ulnar nerve was not purposely located provides a spread and a latency of sensory block equal to that obtained with a 4-injection technique. A shorter performance time is an advantage of this approach.

Treatment of choroidal melanoma by stereotactic radiosurgery.

The case of a 49-year-old woman with an intermediate-sized choroidal melanoma who was treated with stereotactic radiosurgery with good tumour resolution is presented. Sight and globe preservation were achieved. The treatment technique is discussed.

Multiple-injection axillary brachial plexus block: A comparison of two methods of nerve localization-nerve stimulation versus paresthesia.

UNLABELLED: We conducted this prospective study to compare the onset time and the success rate of a multiple-injection axillary brachial plexus block performed by using two methods of nerve localization: paresthesia elicitation or nerve stimulation. Each of the major nerves of the plexus was located by elicitation of a paresthesia (Group PAR; n = 50) or by nerve stimulation (Group PNS; n = 50) and injected with 10 mL of local anesthetic solution. Time to perform the block, onset time of the primary block, time to achieve readiness for surgery, and total anesthetic time were significantly shorter in Group PNS than in Group PAR. The incidence of complete block was larger in Group PNS than in Group PAR (91% vs 76%; P: < 0. 05), and this was related to a larger success rate for anesthetizing the radial and the musculocutaneous nerves (P: < 0.05). The frequency of venous puncture was larger in Group PAR (P: < 0.05). For multiple-injection axillary brachial plexus block, we conclude that nerve stimulation resulted in a greater success rate and a faster onset than paresthesia elicitation, and it should be considered when the radial and musculocutaneous nerve distributions are involved in the surgical area. IMPLICATIONS: Two methods of nerve localization were compared when performing an axillary brachial plexus block by the multiple-injection technique. Nerve stimulation provided a faster onset and a greater incidence of complete block, related to a better success rate for anesthetizing the radial and the musculocutaneous nerves, than paresthesia elicitation.

Iodine-I25 episcleral plaque therapy in uveal melanoma.

PURPOSE: To assess the efficacy of iodine-125 (I-125) episcleral plaque therapy in the management of uveal melanoma with regard to local control, survival, globe preservation and visual outcome. METHODS: Between January 1985 and January 1997, 50 patients with the diagnosis of uveal melanoma were treated with I-125 episcleral plaques. The mean initial tumour height was 5.5 mm (range, 2.0-9.5 mm) and basal diameter 9.5 mm (range, 4.0-14.5 mm). I-125 seeds with a mean activity of 1259.1 MBq were used. The mean apical dose was 80.5 Gy (range, 68.0-95.0 Gy). Scleral dose ranged from 225.0 to 940.0 Gy. Pretreatment visual acuity was 6/60 or better in 43 patients. RESULTS: One patient was lost to follow up and excluded from analysis. The remaining 49 patients had a mean follow up of 39.5 months. There were seven local failures, with a mean duration to tumour progression of 16.7 months. All seven patients were successfully managed with enucleation. Five other enucleations were performed for treatment-related complications. At the time of analysis, 10 patients have died, five of metastatic melanoma. Of the patients with preserved globes, corrected visual acuity was 6/60 or better in 31 patients. CONCLUSIONS: Good local tumour control and survival can be achieved with episcleral plaque therapy. Globe preservation with useful vision was possible in the majority of cases. Our findings are in keeping with other reported series.

A study on the acute anti-ulcer effects of narra (Pterocarpus Indicus Will.) on indomethacin-induced gastric ulcers in male albino rats (Rattus rattus)

Gastric, duodenal and peptic ulcers are collectively ranked as one of the causes of deaths in the country. Management of these diseases comes at a high cost. The researchers explored the use of indigenous narra (Pterocarpus indicus Will.) as a low cost alternative to other expensive medications. This study aimed to determine the presence and degree of ulcerations in Indomethacin-induced gastric ulcers in male albino rats after treatment with either narra leaf decoction or sucralfate. It also aimed to compare the anti-ulcer effects of different dosages of narra leaf decoction with that of sucralfateTwenty-five male rats weighting 115-200 grams were randomly divided into five groups. Gastric ulcers were induced by orally administering 30 mg/kg body weight (BW) of Indomethacin in all rats. Treatments were divided as follows: Negative control (NSS)-10 mg/kg BW normal saline solution; positive control (SUC)-1 g/kg BW sucralfate; Narra group 1 (N1)-3.94 g/kg BW narra leaf decoction; Narra group 2 (N2)-9.89 g/kg BW narra leaf decoction; and, Narra group 3 (N3)-24.84 g/kg BW narra leaf decoction. All treatments were administered using oral gavage and were repeated at intervals of 24 hours for three days. Six hours after the last administration of treatment, the rats were sacrificed and their stomachs excised. Gross analysis was done using the Bests Ulcer Staging Index while histopathological analysis was performed according to the presence and degree of ulcers and hemorrhage. Results were analyzed using Kruskal- Wallis Test for one-way ANOVAOn gross analysis, ulcers and hemorrhages were seen in some of the rat stomachs but the difference in the effects of the treatments on the different groups was not statistically significant. On histopathological analysis, ulcers and hemorrhages were evident in the NSS group but were not noted in the SUC group. The difference between the SUC and NSS groups was statistically significant. Histopathologic studies also showed the following: 2/5 rats had ulcers in Narra group 1; 2/5 in Narra group 2; and, none in Narra group 3 (but all of these rats died before the end of the experiment). However, histopathological differences among the treatment groups were not statistically significantThese findings suggest that narra may have anti-ulcer effects. It is recommended that a dosage higher than 24.84 g/kg BW (the highest narra dosage administered for three days in this experiment) be used in further experiments. The duration of exposure to the drug should also be lengthened. (Author)

Clonidine administered as an axillary block does not affect postoperative pain when given as the sole analgesic.

UNLABELLED: Used as the sole analgesic, clonidine produces analgesia after epidural, intrathecal, and intraarticular administration. We conducted this double-blinded study to determine whether clonidine has analgesic effects when administered into the brachial plexus sheath. At the conclusion of hand or forearm surgery, performed under axillary brachial plexus block, 45 patients were randomly divided into three groups of 15 each to receive, through an axillary catheter, 15 mL of saline (Group Saline), clonidine 150 microg in 15 mL of saline (Group Clonidine), or bupivacaine 15 mL (Group Bupivacaine). The analgesic effects of the three solutions were evaluated for 6 h. Times to onset of pain and to first analgesic request were longer, and the total dose of pain medication was smaller in Group Bupivacaine compared with the other groups. Visual analog scores were significantly lower in Group Bupivacaine. There was no significant difference in time to onset of pain, time to first analgesic request, total dose of pain medication, and visual analog scores between Group Saline and Group Clonidine at any time. We conclude that the administration of clonidine 150 microg into the brachial plexus sheath does not prolong the onset of postoperative pain. IMPLICATIONS: Used as the sole analgesic, clonidine produces analgesia after epidural, intrathecal, and intraarticular administration. It also prolongs the analgesic effect of brachial plexus block when mixed with local anesthetics. In this study, the administration of clonidine 150 microg alone into the brachial plexus sheath did not produce postoperative analgesia.

I.v. clonidine prevents post-extradural shivering.

We have studied the efficacy of i.v. clonidine to prevent shivering in 100 healthy patients who received extradural block for knee arthroscopy. Patients were randomly allocated to two groups. Just before extradural anaesthesia (0 min = baseline), group I (n = 50) received i.v. clonidine 1 microgram kg-1, group II (n = 50) received a saline bolus. Systolic arterial pressure (SAP), heart rate (HR), oxygen saturation (SpO2), cutaneous temperature and level of sedation, were all recorded at baseline and after 10, 20, 30, 45, 60 min. Shivering was evaluated by a blinded investigator for a period of 90 min and was graded as moderate or severe. Three patients in group I shivered compared with 19 in group II (P < 0.001). Patients with severe shivering were seen only in group II. There were no significant differences between the groups during the study period in SAP, HR, SpO2, cutaneous temperature or level of sedation. We conclude that preventive use of i.v. clonidine 1 microgram kg-1 provides a significant reduction in the incidence of post-extradural shivering without clinically relevant adverse side effects.

Transient radicular irritation after spinal anaesthesia with 2% isobaric mepivacaine.

Several cases have been reported in which symptoms suggestive of transient radicular irritation occurred after the use of lidocaine (lignocaine) for spinal anaesthesia. We report three patients in whom we observed similar symptoms after uneventful spinal anaesthesia using isobaric 2% mepivacaine.

Calcium-induced structural transition in the regulatory domain of human cardiac troponin C.

While calcium binding to troponin C (TnC) triggers the contraction of both skeletal and cardiac muscle, there is clear evidence that different mechanisms may be involved. For example, activation of heart myofilaments occurs with binding to a single regulatory site on TnC, whereas activation of fast skeletal myofilaments occurs with binding to two regulatory sites. The physiological difference between activation of cardiac and skeletal myofilaments is not understood at the molecular level due to a lack of structural details for the response of cardiac TnC to calcium. We determined the solution structures of the apo and calcium-saturated regulatory domain of human cardiac TnC by using multinuclear, multidimensional nuclear magnetic resonance spectroscopy. The structure of apo human cardiac TnC is very similar to that of apo turkey skeletal TnC even though there are critical amino acid substitutions in site I. In contrast to the case with the skeletal protein, the calcium-induced conformational transition in the cardiac regulatory domain does not involve an "opening" of the regulatory domain, and the concomitant exposure of a substantial hydrophobic surface area. This result has important implications with regard to potential unique aspects of the interaction of cardiac TnC with cardiac troponin I and of modification of cardiac myofilament regulation by calcium-sensitizer drugs.

Structure of cardiac muscle troponin C unexpectedly reveals a closed regulatory domain.

The regulation of cardiac muscle contraction must differ from that of skeletal muscles to effect different physiological and contractile properties. Cardiac troponin C (TnC), the key regulator of cardiac muscle contraction, possesses different functional and Ca2+-binding properties compared with skeletal TnC and features a Ca2+-binding site I, which is naturally inactive. The structure of cardiac TnC in the Ca2+-saturated state has been determined by nuclear magnetic resonance spectroscopy. The regulatory domain exists in a "closed" conformation even in the Ca2+-bound (the "on") state, in contrast to all predicted models and differing significantly from the calcium-induced structure observed in skeletal TnC. This structure in the Ca2+-bound state, and its subsequent interaction with troponin I (TnI), are crucial in determining the specific regulatory mechanism for cardiac muscle contraction. Further, it will allow for an understanding of the action of calcium-sensitizing drugs, which bind to cardiac TnC and are known to enhance the ability of cardiac TnC to activate cardiac muscle contraction.

Refined X-ray crystallographic structure of the poliovirus 3C gene product.

The X-ray crystallographic structure of the recombinant poliovirus 3C gene product (Mahoney strain) has been determined by single isomorphous replacement and non-crystallographic symmetry averaging and refined at 2.1 A resolution. Poliovirus 3C is comprised of two six-stranded antiparallel beta-barrel domains and is structurally similar to the chymotrypsin-like serine proteinases. The shallow active site cleft is located at the junction of the two beta-barrel domains and contains a His40, Glu71, Cys147 catalytic triad. The polypeptide loop preceding Cys147 is flexible and likely undergoes a conformational change upon substrate binding. The specificity pockets for poliovirus 3C are well-defined and modeling studies account for the known substrate specificity of this proteinase. Poliovirus 3C also participates in the formation of the viral replicative initiation complex where it specifically recognizes and binds the RNA stem-loop structure in the 5' non-translated region of its own genome. The RNA recognition site of 3C is located on the opposite side of the molecule in relation to its proteolytic active site and is centered about the conserved KFRDIR sequence of the domain linker. The recognition site is well-defined and also includes residues from the amino and carboxy-terminal helices. The two molecules in the asymmetric unit are related by an approximate 2-fold, non-crystallographic symmetry and form an intermolecular antiparallel beta-sheet at their interface.