Acute traumatic spinal cord injury, 1993-2000A population-based assessment of methylprednisolone administration and hospitalization

BACKGROUND: Administration of methylprednisolone sodium succinate (MPSS) after acute traumatic spinal cord injury (TSCI) is controversial. This study compared differences in acute care charge, hospital stay, and related variables as a function of MPSS receipt. METHODS: Determinants of MPSS administration were examined after acute TSCI for South Carolina patients during the period 1993 to 2000 in a multivariate logistic regression model. RESULTS: Administration of MPSS was documented for 48.7% of 1,227 randomly selected patients with TSCI. Patients admitted via trauma centers and emergency departments were more likely to receive MPSS (trama center level 1 odds ratio [OR], 4.06; 95% CI confidence interval [CI], 2.11-7.83; emergency department OR, 1.64; 95% CI, 1.20-2.23). Hospital charge and length of stay were significantly higher for MPSS recipients. CONCLUSIONS: The study findings indicate MPSS use is associated with higher acute care charges and longer hospital stays. These findings suggest the need for outcome studies to assess the long-term benefits of MPSS administration.     

Quantitative structure-activity relationship of triazine-antifolate inhibition of Leishmania dihydrofolate reductase and cell growth

Quantitative structure-activity relationships have been formulated for the inhibition of Leishmania major dihydrofolate reductase (DHFR) and for inhibition of promastigote cell growth by a series of 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(3-substituted-phenyl)-s-triazine s. The inhibition of DHFR is best correlated by a modified variable for hydrophobicity of the 3-X substituent (pi'3), an alkoxy group indicator variable (IOR), a disposable parameter (beta) obtained by iteration, and a variable that parameterizes steric effects (MR) in the equation, log 1/Ki = 0.65 pi'3 - 1.22 log (beta X 10 pi'3 + 1) - 1.12IOR + 0.58MRY + 5.05 (r = 0.965). The EC50 values for triazine inhibition of L. major cell growth in culture are correlated by the equation log 1/EC50 = 0.21 pi 3 + 0.44 log 1/Ki + 0.53 (r = 0.960). When compared to DHFR from human, other vertebrates, and E. coli, L. major DHFR differs in that it optimally binds triazine congeners that are much more hydrophobic. Furthermore, in contrast to other DHFR's studied, triazine binding to L. major DHFR does not seem to be influenced by the electronic characteristics of the 3-X substituent of the parent triazine molecule. However, L. major DHFR is more sensitive to the steric effects and polarizability of the 3-X substituent. Our results indicate that triazines inhibit L. major promastigote growth via direct inhibition of DHFR as is shown by the good correlation between log 1/Ki values for inhibition of the purified enzyme and log 1/EC50 values for inhibition of cell culture growth. Two lipophilic, sterically large analogues of this triazine series showed selectivity for L. major DHFR over human DHFR. Further optimization of the MR and IOR terms in the above QSAR equations may provide even more selective inhibitors.     

The relative toxicity of substituted phenols reported in cigarette mainstream smoke.

Cigarette mainstream smoke (MS) contains a number of structurally diverse substituted phenols. Recent quantitative structure activity relationship (QSAR) studies on phenols show that substituted phenols with electron-releasing groups can form potentially toxic phenoxyl-free radicals. In contrast, substituted phenols with electron-withdrawing groups do not form phenoxyl-free radicals but exert their toxicity primarily through lipophilicity. The chemical structures of 253 different substituted phenols reported in MS have been described in sufficient detail to allow identification of the individual compounds. From a laterally validated equation based on published data on the toxic effects of phenols on cultured cells, the relative toxicity, on a molar basis, of the 253 MS phenols has been determined. Based on this scheme, the most toxic phenols in MS include, in descending order of toxicity, 2-(dimethylamino)-phenol, 2-ethyl-6-methyl-1,4-benzenediol, 2-methoxy-1,4-benzenediol, and 4-ethyl-2-methoxy-6-methylphenol. The least toxic phenols include, in ascending order of toxicity, 4-hydroxybenzoic acid and 3-hydroxybenzenepropanoic acid. In the human exposure situation, the toxicity of MS phenols is a complex interaction, with contributions made by the following factors: toxicity per mole; MS concentration; synergistic, additive or antagonistic interactions with other MS components; host susceptibility; metabolism; and individual smoking behavior and inhalation patterns. In the absence of data to the contrary, reduction in the number and concentration of toxic MS smoke components may be considered to be advantageous. Studies of this type can play an important role in identifying MS components for reduction or removal.     

Structure-activity relationships of antineoplastic agents in multidrug resistance

Clinical resistance to many antineoplastic agents is a major cause of treatment failure. The well-documented phenomenon addressed as multidrug resistance (MDR) allows cells to withstand exposure to lethal doses of drugs with dissimilar chemical structures, modes of action, and physicochemical properties. In one of the earliest studies on MDR, Biedler and Riehm in an attempt to explain the cross-resistance profile of actinomycin D resistant Chinese hamster cells suggested that molecular weight was an important determinant. Our statistical analysis of their data validates their claim and indeed strongly demonstrates that cross resistance is enhanced by the increased size and hydrophobicity of the antitumor agent. Our preliminary studies with methotrexate-resistant L1210 cells indicates that cross resistance is increased in the case of moderate-sized, hydrophilic drugs. These two studies and others suggest that current chemotherapy regimens may be improved by treating resistant cells with antineoplastic agents displaying physicochemical characteristics opposite to that of the original inducing agent.     

A population-based outcomes study of persons hospitalized with traumatic brain injury: operations of the South Carolina Traumatic Brain Injury Follow-up Registry

OBJECTIVE: To describe the design and operations of the South Carolina Traumatic Brain Injury (TBI) Follow-up Registry. DESIGN: Statewide prospective cohort study. SETTING: State of South Carolina. PARTICIPANTS: 2118 persons discharged from acute care hospitals after experiencing TBI. INTERVENTION: Telephone interviews. MAIN OUTCOME MEASURES: Service needs, alcohol and drug use, psychosocial health, health-related quality of life, functional status, symptoms of TBI, employment, global life satisfaction, and death. RESULTS: Selected initial and 1-year follow-up findings concerning demographic, insurance status, income, and employment factors. CONCLUSIONS: Population-based outcome studies that describe longer term problems associated with TBI, the need for services, and estimated disability could be useful to inform public policy.     

Self-reported psychosocial health among adults with traumatic brain injury

OBJECTIVE: To measure the subjective psychosocial health of a population-based sample of adults with traumatic brain injury (TBI). DESIGN: Retrospective, cohort study involving a 1-year postinjury interview. SETTING: Sixty-two acute care, nonfederal hospitals in South Carolina. PARTICIPANTS: Persons (> or =15y) hospitalized with TBI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The psychosocial health scales of the Medical Outcomes Study 36-Item Short-Form Health Survey. RESULTS: Of the 7612 participants, 29% reported poor psychosocial health. Factors associated with poor psychosocial well-being included younger age, female sex, Medicaid coverage, no health insurance, inadequate or moderate social support, comorbidities (eg, a preinjury substance abuse problem), cognitive complaints, and some or a lot of limitation with activities of daily living. Only 36% of participants who reported poor psychosocial health reported receiving any mental health services. CONCLUSIONS: A substantial proportion of persons hospitalized with TBI reported poor psychosocial health at 1 year postinjury. To optimize recovery, clinicians need to ensure that patients' psychosocial health needs are addressed during the postacute period.     

Patterns of language and auditory dysfunction in 6-year-old children with epilepsy

In a previous study we reported difficulty with expressive language and visuoperceptual ability in preschool children with epilepsy and otherwise normal development. The present study analysed speech and language dysfunction for each individual in relation to epilepsy variables, ear preference, and intelligence in these children and described their auditory function. Twenty 6-year-old children with epilepsy (14 females, 6 males; mean age 6:5 y, range 6 y–6 y 11 mo) and 30 reference children without epilepsy (18 females, 12 males; mean age 6:5 y, range 6 y–6 y 11 mo) were assessed for language and auditory ability. Low scores for the children with epilepsy were analysed with respect to speech-language domains, type of epilepsy, site of epileptiform activity, intelligence, and language laterality. Auditory attention, perception, discrimination, and ear preference were measured with a dichotic listening test, and group comparisons were performed. Children with left-sided partial epilepsy had extensive language dysfunction. Most children with partial epilepsy had phonological dysfunction. Language dysfunction was also found in children with generalized and unclassified epilepsies. The children with epilepsy performed significantly worse than the reference children in auditory attention, perception of vowels and discrimination of consonants for the right ear and had more left ear advantage for vowels, indicating undeveloped language laterality.     

Experiences of persons with epilepsy and their families as they look for medical and community care: a focus group study from South Carolina

Epilepsy affects a larger number of individuals than previously thought-up to 2% of the population-and its effects reach further. Yet epilepsy, with its associated lingering stigma and fear, has remained in the background in terms of services and research. Traditional quantitative research often falls short when trying to describe the impact of epilepsy on the lives of individuals and their families. In the present study, focus groups were held throughout South Carolina to discuss individuals' experiences with accessing epilepsy-related services and health care, and what life with epilepsy is like. Following qualitative data analysis, findings included two themes. One theme focuses on the ongoing search for services and help. The second theme concerns the experiences of living life with epilepsy. Also highlighted are recommendations for potential improvements in public awareness and professional training, and helpful interventions.