Controversies in medical management of intracerebral hemorrhage

Intracerebral hemorrhage (ICH) is a devastating form of stroke that is associated with a very high mortality rate. Both medical therapies to control blood pressure, blood sugar, temperature, and surgical therapies to remove or contain clot remain controversial. The decision when to offer medical versus surgical treatment is very challenging and uncertain. Novel therapies are currently being developed and may be successful in containing the neurological injury associated with ICH. This review will highlight the controversies underlying medical management of ICH and the current ongoing research in the field.     

Experimental allergic encephalomyelitis: a misleading model of multiple sclerosis

Despite many years of intensive research, multiple sclerosis (MS) defies understanding and treatment remains suboptimal. The prevailing hypothesis is that MS is immune mediated and that experimental allergic encephalomyelitis (EAE) is a suitable model to elucidate pathogenesis and devise therapy. This review examines critically the validity that EAE is an adequate and useful animal model of MS and finds credible evidence lacking. EAE represents more a model of acute central nervous system inflammation than the counterpart of MS. We propose to reconsider the utilization of EAE, especially when this model is used to define therapy. This will also force us to examine MS without the restraints imposed by EAE, as to what it is, rather than what it looks like.     

Defective ATM-p53-mediated apoptotic pathway in multiple sclerosis

Defective elimination of autoreactive cells is thought to play a role in the development of autoimmune diseases including multiple sclerosis (MS). We examined the activation of the ATM-CHK2-p53 pathway in MS patients after subjecting their peripheral blood mononuclear cells to gamma-irradiation. We found that peripheral blood mononuclear cells from a subset of MS patients show resistance to cell death induced by irradiation. This defect is due to impaired constitutive expression and activation of ATM (ataxia telangiectasia mutated), resulting in impaired stabilization of p53. We predict that these fundamental defects likely alter the regulation of the immune population of cells in MS and may contribute to the development or progression of the disease.     

Ketamine as adjuvant analgesic to opioids: a quantitative and qualitative systematic review

Animal studies on ketamine and opioid tolerance have shown promising results. Clinical trials have been contradictory. We performed a systematic review of randomized, double-blind clinical trials of ketamine added to opioid analgesia. Thirty-seven trials with 51 treatment arms and 2385 patients were included. Studies were divided into 5 subgroups: IV ketamine as single dose (n = 11), continuous infusion (n = 11), patient-controlled analgesia (PCA) (n = 6), epidural ketamine with opioids (n = 8), and studies in children (n = 4). Outcome measures included pain scores, time to first request for analgesia, supplemental analgesics, and adverse events. Efficacy was estimated by statistical significance (P < 0.05) of outcome measures as reported in studies and also by calculation of weighted mean difference for pain scores during the first 24 h after surgery. As compared to morphine alone, IV PCA with ketamine and morphine did not improve analgesia. Intravenous infusion of ketamine decreased IV and epidural opioid requirements in 6 of 11 studies. A single bolus dose of ketamine decreased opioid requirements in 7 of 11 studies. Five of 8 trials with epidural ketamine showed beneficial effects. Adverse effects were not increased with small dose ketamine. We conclude that small dose ketamine is a safe and useful adjuvant to standard practice opioid-analgesia.     

Local anaesthesia for carotid endarterectomy

Carotid endarterectomy is preventative surgery aimed at reducingthe rate of stroke in patients at high risk of such an event.Approximately 1% of the British population over 75 years oldwill die as a result of carotid artery disease each year. Performing a carotid endarterectomy itself has considerablerisk. The rate of perioperative stroke has been reported as2.2% overall – 1.7% in patients with no prior historyof CVA (cardiovascular accident) and 4.2% in those with a previousstroke. Many of these patients have widespread arteriopathicand ischaemic heart disease, chronic obstructive pulmonary diseaseor diabetes. In addition, they may be smokers and elderly. Theco-morbidity associated with carotid disease is therefore considerable.The combined perioperative mortality from myocardial infarctionas well as stroke is likely to be less than 2%.     

Substance abuse in schizophrenia. A Singapore perspective

Background Most of the information on the prevalence and patterns of substance abuse in patients with schizophrenia has been from studies conducted in North America and Europe and data from Asian countries are conspicuously lacking. This study was undertaken with the aim to identify the prevalence and patterns of substance abuse among patients with first-episode schizophrenia in the city-state of Singapore. Methods All new patients with a diagnosis of first-episode schizophrenia or schizophreniform disorder who were seen in one calendar year in the only state mental institute in Singapore and its affiliated outpatient clinics were evaluated for a lifetime history of substance use. Results In a sample of 272 patients, 201 (73.6 %) were abstainers, 43 (15.8 %) had “mild” substance use and 28 (10.3 %) had “heavy” use patterns. Alcohol was the most frequently abused substance. The substance users were more likely to be males and were more likely to have a criminal record than abstainers. Conclusions To our knowledge, this is the first study that examines the co-morbidity of substance abuse in schizophrenia in an Asian population. Our findings once again highlight the fact that patients with schizophrenia are at a high risk for substance abuse. Accepted: 20 February 2002     

Analysis of lobar differences in particle deposition in the human lung

Lung diseases caused by the inhalation of various particulate pollutants have often been reported to occur at specific sites in the lung with some diseases preferentially occurring in one of the lobes. Models for the dosimetry of particulate matter in the lung, therefore, need to be developed at a level of resolution that allows for the study of lobar- and airway-specific patterns of deposition. Using an approach best described as a combination of asymmetric and symmetric approaches to modeling lung geometry, we calculated deposition of particulate matter (PM) ranging from ultrafine to coarse particles in each airway down to the level of the lobar bronchi. Further down the airway tree, we calculated deposition averaged over an airway generation in each lung lobe. We compared our results for regional and lobar deposition with various experimental data as well as with results from other models. The calculated results compared reasonably well with experimental data. Significant variations in deposition were observed among the lobar bronchi as well as among the five lobes. The differences among the lobes were accentuated as one examined generation-specific deposition. Deposition per unit surface area of each lobar bronchus was considerably elevated relative to that calculated for the whole lung. The relative distribution of aerosol deposited per unit surface area among the lobar bronchi was altered by breathing condition and aerosol size. Our observations suggest that a multiple-path model that incorporates the heterogeneous structure of airways in the lung is likely to reduce uncertainties in PM health risk assessments.