Malignant hyperthermia

Malignant hyperthermia is a potentially fatal pharmacogenetic disease triggered by volatile anesthetics and/or succinylcholine. Dysregulation of intracellular calcium homeostasis is the trigger of the acute crisis. Malignant hyperthermia crisis correspond to an hypermetabolic state, which occurred acutely and interesting skeletal muscular cell. Early manifestations grouped tachycardia, tachypnea, masseter spasm, mixed acidosis and raise of the end expiratory CO2 pressure. Hyperthermia is a late sign, rhabdomyolysis is a sign of the severity of the malignant hyperthermia. The successful treatment is based on an early diagnosis, immediately interruption of triggering agents, intravenous administration of Dantrolene in sufficient dosage and starting of adequate symptomatic treatment. Prevention of this complication is based on asking the patient about genetic predisposition to malignant hyperthermia. Confirmation of the susceptibility to malignant hyperthermia can be provided by in vitro contracture test with halothane or caffeine after muscle biopsy.     

Progressive encephalomyelitis with rigidity presenting as a stiff-person syndrome

Diagnosis criteria of stiff-person syndrome (SPS) include progressive, fluctuating muscular rigidity and spasms with normal neurological examination. The presence of unusual features such as prominent limb rigidity with segmental signs and contracture, evidence of brainstem dysfunction, profound autonomic disturbances, CSF pleiocytosis or MRI abnormalities in patients with SPS presentation allows to classify these patients as progressive encephalomyelitis with rigidity (PER). We report a 50 year-old woman suffering from severe painful spasms of abdominal wall and limb muscles. Neurological examination showed pyramidal signs. EMG disclosed continuous muscle activity with superimposed discharges. Treatment with high doses of diazepam and baclofen led to moderate improvement of generalised stiffness. However, the right arm became more rigid with oedema and vasomotor changes. Subsequently, bilateral nystagmus and internuclear opthalmplegia appeared. There was mild CSF pleiocytosis. Associated auto-immune thyroiditis was found with positive anti-microsome antibodies and decreased thyroid hormones. Search for profound neoplasm was negative. The patient had three subacute bouts then she improved with methylprednisolone. The initial clinical presentation mimicking a SPS with subsequent diffuse involvement of the central nervous system and a striking localisation of a severe rigidity to one arm allowed to suspect the diagnosis of PER. The relationship between SPS and PER remains unclear because of the rarity of these disorders. The observation reported in this paper gives evidence that both the disorders are probably two clinical presentations of the same pathogenic process.     

Impact of reporting delay and reporting error on cancer incidence rates and trends

BACKGROUND: Cancer incidence rates and trends are a measure of the cancer burden in the general population. We studied the impact of reporting delay and reporting error on incidence rates and trends for cancers of the female breast, colorectal, lung/bronchus, prostate, and melanoma. METHODS: Based on statistical models, we obtained reporting-adjusted (i.e., adjusted for both reporting delay and reporting error) case counts for each diagnosis year beginning in 1981 using reporting information for patients diagnosed with cancer in 1981-1998 from nine cancer registries that participate in the Surveillance, Epidemiology, and End Results (SEER) program. Joinpoint linear regression was used for trend analysis. All statistical tests are two-sided. RESULTS: Initial incidence case counts (i.e., after the standard 2-year delay) accounted for only 88%-97% of the estimated final counts; it would take 4-17 years for 99% or more of the cancer cases to be reported. The percent change between reporting-adjusted and unadjusted cancer incidence rates for the 1998 diagnosis year ranged from 3% for colorectal cancers to 14% for melanoma in whites and for prostate cancer in black males. Reporting-adjusted current incidence trends for breast cancer and lung/bronchus cancer in white females showed statistically significant increases (estimated annual percent change [EAPC] = 0.6%, 95% confidence interval [CI] = 0.1% to 1.2%) and 1.2%, 95% CI = 0.7% to 1.6%, respectively), whereas trends for these cancers using unadjusted incidence rates were not statistically significantly different from zero (EAPC = 0.4%, 95% CI = -0.1% to 0.9% and 0.5%, 95% CI = -0.1% to 1.1%, respectively). Reporting-adjusted melanoma incidence rates for white males showed a statistically significant increase since 1981 (EAPC = 4.1%, 95% CI = 3.8% to 4.4%) in contrast to the unadjusted incidence rate, which was most consistent with a flat or downward trend (EAPC = -4.2%, 95% CI = -11.1% to 3.3%) after 1996. CONCLUSIONS: Reporting-adjusted cancer incidence rates are valuable in precisely determining current cancer incidence rates and trends and in monitoring the timeliness of data collection. Ignoring reporting delay and reporting error may produce downwardly biased cancer incidence trends, particularly in the most recent diagnosis years.     

Goal setting and attainment in Alzheimer's disease patients treated with donepezil

OBJECTIVES: To understand the treatment goals of Alzheimer's disease (AD) patients, carers, and physicians; to estimate whether clinically important goals are met during treatment with donepezil; and to compare a measure of goal attainment with standard measures used to evaluate AD treatment. METHODS: In a 12 month phase IV trial, 108 patients with mild to moderate AD, their primary carers, and treating physicians set goals assigned to five domains, using Goal Attainment Scaling (GAS) as the primary outcome. Goal attainment was assessed quarterly. GAS scores were correlated with standard outcomes, including the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-cog), and the Clinician's Interview-Based Impression of Change-Plus (CIBIC-plus). RESULTS: Physicians set fewer goals (342, mean (SD) per patient=3 (1)) than patients/carers (855, mean=9 (3)), particularly in leisure (20% by physicians compared with 76% by patients/carers), and social interaction (24% versus 49%). Physicians observed statistically significant improvement in global goal attainment for six months, and patients/carers for nine months. Patients/carers described consistent goal attainment, whereas physicians observed variable effects, such as decline in cognition but improved social interaction and behaviour. Physician global GAS scores correlated highly with the CIBIC-plus at weeks 12 (r= -0.82) and 52 (r=-0.80), but not with the ADAS-cog (r=0.12 and r=-0.45, respectively). Patient/carer global GAS scores correlated moderately with the physician's CIBIC-plus (week 12 r=-0.51; week 52 r=-0.56), and nominally with the ADAS-cog. CONCLUSIONS: Patients/carers and physicians differ in their expectations and impressions of treatment effects. Clinically important changes correlated only modestly with psychometric tests. Attainment of treatment goals does not accord with a simplistic model in which successful AD treatment means that all declines uniformly improve.     

Hematopoietic growth factors, dendritic cell biology, and vaccine therapy of cancer

Hematopoietic growth factors have made it possible to collect, manufacture, and engineer dendritic cells ex vivo for clinical use and expand dendritic cell subsets in vivo when administered to patients. Dendritic cells are important vectors in the induction of an effective immune response against infection and neoplastic disease. Antigens alone, even those preprocessed to bind to antigen-presenting major histocompatibility complex class I and II molecules, are insufficient to regulate effective T-cell-mediated immunity. Activated dendritic cells are essential to this task. Studies of dendritic cell biology in the laboratory and preclinical studies have facilitated the implementation of clinical trials using dendritic cells in the treatment of melanoma and other cancers. Dendritic cell subset functional differences, effective tumor target antigen loading of dendritic cells for presentation to immune effector cells, dendritic cell maturation, the route of dendritic cell administration to humans, and immunologic monitoring are parameters that require vigorous study in the context of dendritic cell immunotherapy of cancer.     

Time-dependent influence of sensorimotor set on automatic responses in perturbed stance

 These experiments tested the hypothesis that the ability to change sensorimotor set quickly for au-tomatic responses depends on the time interval between successive surface perturbations. Sensorimotor set refers to the influence of prior experience or context on the state of the sensorimotor system. Sensorimotor set for postural responses was influenced by first giving subjects a block of identical backward translations of the support surface, causing forward sway and automatic gastrocnemius responses. The ability to change set quickly was inferred by measuring the suppression of the stretched antagonist gastrocnemius responses to toes-up rotations causing backward sway, following the translations. Responses were examined under short (10–14 s) and long (19–24 s) inter-trial intervals in young healthy subjects. The results showed that subjects in the long-interval group changed set immediately by suppressing gastrocnemius to 51% of translation responses within the first rotation and continued to suppress them over succeeding rotations. In contrast, subjects in the short-interval group did not change set immediately, but required two or more rotations to suppress gastrocnemius responses. By the last rotation, the short-interval group suppressed gastrocnemius responses to 33%, similar to the long-interval group of 29%. Associated surface plantarflexor torque resulting from these responses showed similar results. When rotation and translation perturbations alternated, however, the short-interval group was not able to suppress gastrocnemius responses to rotations as much as the long-interval group, although they did suppress more than in the first rotation trial after a series of translations. Set for automatic responses appears to linger, from one trial to the next. Specifically, sensorimotor set is more difficult to change when surface perturbations are given in close succession, making it appear as if set has become progressively stronger. A strong set does not mean that responses become larger over consecutive trials. Rather, it is inferred by the extent of difficulty in changing a response when it is appropriate to do so. These results suggest that the ability to change sensorimotor set quickly is sensitive to whether the change is required after a long or a short series of a prior different response, which in turn depends on the time interval between successive trials. Different rate of gastrocnemius suppression to toes-up rotation of the support surface have been reported in previous studies. This may be partially explained by different inter-trial time intervals demonstrated in this study. Received: 7 October 1997 / Accepted: 31 August 1998