Search PubMed⌕ Search

Biomedical subjects

L J Cook

Publications and source records attributed to L J Cook.

At least 19 recordsLinked to original sources

The fast and the fatal: street racing fatal crashes in the United States.

The objective of this study was to determine the annual incidence of fatal motor vehicle crashes involving street racing and to describe the characteristics of these crashes compared to other fatal crashes in the United States. The National Highway Traffic Safety Administration Fatality Analysis Reporting System data for 1998-2001 were used for the analyses. There were 149 568 fatal crashes and 315 (0.21%) involved street racing and 399 fatalities occurred in these crashes. In contrast to other fatal crashes, street racing fatal crashes were more likely to occur on urban roadways and were nearly six times more likely to occur at travel speeds> or = 65 mph. Compared with other drivers involved in fatal crashes, street racers were more likely to be teenagers, male, and have previous crashes and driving violations. Street racing involves risky driving behaviors and warrants further attention.

Accident Proneness↗

Genetic and functional analyses of FH mutations in multiple cutaneous and uterine leiomyomatosis, hereditary leiomyomatosis and renal cancer, and fumarate hydratase deficiency.

Germline mutations of the fumarate hydratase (FH, fumarase) gene are found in the recessive FH deficiency syndrome and in dominantly inherited susceptibility to multiple cutaneous and uterine leiomyomatosis (MCUL). We have previously reported a number of germline FH mutations from MCUL patients. In this study, we report additional FH mutations in MCUL and FH deficiency patients. Mutations can readily be found in about 75% of MCUL cases and most cases of FH deficiency. Some of the more common FH mutations are probably derived from founding individuals. Protein-truncating FH mutations are functionally null alleles. Disease-associated missense FH changes map to highly conserved residues, mostly in or around the enzyme's active site or activation site; we predict that these mutations severely compromise enzyme function. The mutation spectra in FH deficiency and MCUL are similar, although in the latter mutations tend to occur earlier in the gene and, perhaps, are more likely to result in a truncated or absent protein. We have found that not all mutation-carrier parents of FH deficiency children have a strong predisposition to leiomyomata. We have confirmed that renal carcinoma is sometimes part of MCUL, as part of the variant hereditary leiomyomatosis and renal cancer (HLRCC) syndrome, and have shown that these cancers may have either type II papillary or collecting duct morphology. We have found no association between the type or site of FH mutation and any aspect of the MCUL phenotype. Biochemical assay for reduced FH functional activity in the germline of MCUL patients can indicate carriers of FH mutations with high sensitivity and specificity, and can detect reduced FH activity in some patients without detectable FH mutations. We conclude that MCUL is probably a genetically homogeneous tumour predisposition syndrome, primarily resulting from absent or severely reduced fumarase activity, with currently unknown functional consequences for the smooth muscle or kidney cell.

Amino Acid Metabolism, Inborn Errors↗

Shoulder belts in motor vehicle crashes: a statewide analysis of restraint efficacy.

The purpose of our study was to evaluate the impact of shoulder belt use on motor vehicle crash ejection, morbidity and mortality. We analyzed motor vehicle crash records linked to hospital inpatient data for front seat occupants of passenger cars in Utah between 1994 and 1996 (n = 103,035). Stochastic simulations were used to adjust for possible seatbelt misclassification. There were 276 (0.3%) occupants coded as using only a shoulder belt. The adjusted odds of ejection for shoulder only belted occupants was higher compared to lap-shoulder belted (odds ratio (OR) = 18.9; 95% confidence interval (CI) = 15.1, 25.1) and lap only belted occupants (OR = 4.3; 95% Cl = 2.9, 7.7). There was no difference in the odds of ejection for an occupant using a shoulder belt only and an occupant using no seatbelt (OR = 1.1; 95% CI = 1.0, 1.3). Occupants using a shoulder belt only were more likely to sustain a fatal or hospitalizing injury than lap-shoulder belted (OR = 2.3; 95% Cl = 1.9, 3.0), and lap only belted occupants (OR = 1.8; 95% CI = 1.3, 2.7), while controlling for other covariates. Occupants using only a shoulder belt had the same odds of a fatal or hospitalizing injury as unbelted occupants (OR = 1.1; 95% Cl = 0.9, 1.4). Average hospital inpatient length of stay, charges and injury severity scores were similar for all restraint types. These results stress the need for the use of a lap belt in conjunction with the shoulder belt.

Accidents, Traffic↗

Snowmobile injuries in Utah.

OBJECTIVE: To describe the epidemiology of snowmobile injuries in Utah. METHODS: Analysis of probabilistically linked statewide emergency department (ED), hospital admission, and death certificate data for 1996 and 1997. RESULTS: There were 625 cases of snowmobile-related injuries. The majority (83%) were evaluated in the ED only. Median ED patient age was 29 years (range 3-74 years), and 66% were male. The leading diagnoses were open wounds to the head (7.8%), back strains (5.4%), and contusions of the trunk and lower extremities (5.2% and 5.0%, respectively). An Injury Severity Score (ISS) of > or = 4 (range 1-75) was found in 37% of the ED patients. The median charge was $373 per patient, with two-year cumulative charges of $266,283. One hundred seven patients required inpatient hospital care. Median inpatient age was 32 years (range 4-92 years), and 60% were male. Leading inpatient diagnoses were fracture of the vertebral column (9.3%), lower extremity fracture (9.3%), upper extremity fracture (6.5%), and pelvis fracture (3.7%). An ISS of > or = 4 (range 1-38) was found in 70% of the hospitalized patients. Average length of stay was 3 days, with a range of 1 to 68 days. Median inpatient charge was $6,003 per patient, with two-year cumulative charges of $1,333,218. Ten inpatients required transfer for rehabilitation or skilled nursing care. There were a total of six fatalities, three of which occurred in the ED, one in the inpatient population, and two identified from the death certificate database. CONCLUSIONS: By combining ED, inpatient, and death certificate data sets, probabilistic linkage provides a comprehensive description of snowmobile-related injuries and a baseline evaluation of morbidity, mortality, and financial burden.

Adolescent↗

A population-based study of crashes involving 16- and 17-year-old drivers: the potential benefit of graduated driver licensing restrictions.

OBJECTIVE: To evaluate the potential effectiveness of graduated driver licensing programs using population-based linked data for motor vehicle crashes (MVCs) that involved teenaged drivers (TDs). METHODS: Utah crash, inpatient hospital discharge, and emergency department databases were analyzed and probabilistically linked. We computed hospital charges and compared violations, contributing factors, seatbelt use, and passengers for TDs (16-17 years old) relative to adult drivers (18-59 years old). RESULTS: TDs comprised 5.8% of the study population, but were involved in 19.0% of MVCs. TD crashes resulted in $11 million in inpatient hospital charges and 158 fatalities. TD crashes were 1.70 times (95% confidence interval [CI]: 1.34, 2.04) less likely to result in fatal injury to drivers than were crashes that involved adult drivers, but TDs were 2.20 times (95% CI: 1.96, 2.47) more likely to receive citations. The following were findings of the study: 1) 11% of all TD crashes but 19% of fatal TD crashes occurred between 2200 and 0600 hours; 2) TDs used seatbelts less often than did adult drivers (79.1% vs 84.4%) and less often with passengers present (81.9% vs 75.0%; 3) TDs were 1.72 times (95% CI: 1.38, 2.14) more likely to be involved in crashes that resulted in seriously or fatally injured occupants when driving with passengers than when driving alone. CONCLUSIONS: TDs are overrepresented in MVCs. TD crashes have a higher fatality rate at night, and TDs wear seatbelts less often than do adult drivers. Passengers affect TD crash characteristics. Graduated driver licensing programs that target state-specific characteristics of TDs may decrease morbidity and mortality.

Accidents, Traffic↗

A population-based assessment of pediatric all-terrain vehicle injuries.

OBJECTIVE: To describe the types of injuries sustained by children who ride all-terrain vehicles (ATVs), to estimate the hospital charges associated with these injuries, and to determine adherence to existing rules and regulations governing ATV use. METHODS: Analysis of statewide hospital admissions (1992-1996) and emergency department (ED) visits (1996) in Utah. All patients who were younger than 16 years and had an external cause of injury code for ATV use were included. RESULTS: In 1996, 268 ED visits by children involved an ATV. Boys were twice as commonly injured as girls (male:female ratio: 2.1:1), and skin and orthopedic injuries were most frequent. The median ED charge was $368, and ED charges for these patients totaled $138 000. From 1992 to 1996, 130 children were hospitalized as a result of injuries sustained during ATV use, with median charges of $4240 per admission. Male to female ratio was 2.7:1, and the average age was 11.2 +/- 3.6 years. Mean injury severity score was 8.0 +/- 6.0, and median length of stay was 2 days (range: 0-43 days). Orthopedic injuries were most frequent, but 25% (n = 32) of children sustained head or spinal cord injury. Most children (94%) were discharged from the hospital, but 8 children died as a result of their injuries. Utah regulations prohibit children who are younger than 8 years from driving an ATV and advise against carrying passengers on ATVs. However, 25% (n = 15) of all injured children who were younger than 8 were driving the ATV when injured, and 15% (n = 60) of injured children were passengers on ATVs. Four of the 8 fatally injured children were younger than 8, and all were driving the ATV at the time of the crash. Finally, the estimated injury rate per 100 registered ATVs is significantly higher for children than for adults (3.41 vs 1.71). CONCLUSIONS: ATV use results in significant injuries to children. Efforts to educate parents regarding the risks of ATV use, proper supervision, and use of safety equipment are warranted. Manufacturers of ATVs should continue to improve the safety profile of these inherently unstable vehicles.

Accidents, Traffic↗

Probabilistic record linkage: relationships between file sizes, identifiers and match weights.

This study investigates relationships between file sizes, amounts of information contained in commonly used record linkage variables, and the amount of information needed for a successful probabilistic linkage project. We present an equation predicting the amount of information needed for a successful linkage project. Match weights for variables commonly used in record linkage are measured using artificially created databases. Linkage algorithms were successful when the sum of minimum weights for variables used in a linkage exceeded the predicted cutoff. Linkage results were acceptable when this sum was near the predicted cutoff. This technique enables researchers to determine if enough information exists to perform a successful probabilistic linkage.

Algorithms↗

Adults and children in severe motor vehicle crashes: a matched-pairs study.

STUDY OBJECTIVE: Many articles report seat belt injuries to children. This study examines the effect of child versus adult age and seat belt use on outcome in severe motor vehicle crashes. METHODS: A population-based data set of all motor vehicle crashes statewide was analyzed by using matched-pairs logistic regression. Subjects were participants in motor vehicle crashes in which at least one occupant was killed or hospitalized and at least one was a child (age <15 years). Only passengers in cars, vans, and the front of light trucks were considered. Unique matched pairs were formed of one adult and one child from the same vehicle. The main outcome measure was death or hospitalization. Covariates were seat belt use and front or back seat position. RESULTS: Overall, 413 pairs were analyzed. Seat belt use in these severe crashes was low for children and adults (40% versus 45%). Children more often sat in the back seat (74% versus 31% for adults). Risk of death was similar (7% for children and 8% for adults), but the percentage killed or hospitalized differed (13% for children and 28% for adults; odds ratio [OR] 2.5; 95% confidence interval [CI] 1.8 to 3.7). After controlling for seat belt use and seat position, adults remained at a similarly increased risk compared with children (OR 2.6; 95% CI 1.6 to 4.2). The back seat was much safer than the front seat (OR 5.5; 95% CI 3.7 to 8.1). An adult's nonuse of restraints was strongly predictive of a child's nonuse. CONCLUSION: Seat belts were at least as protective for children as for adults, but only 40% of the children in these severe crashes were restrained.

Accidents, Traffic↗

Motor vehicle crash characteristics and medical outcomes among older drivers in Utah, 1992-1995.

STUDY OBJECTIVE: We sought to compare the characteristics and medical outcomes of motor vehicle crashes for drivers 70 years and older with those of drivers between the ages of 30 and 39 years. METHODS: We probabilistically linked statewide motor vehicle crash and hospital discharge data between the years of 1992 and 1995 for the state of Utah. We calculated the odds of older drivers exhibiting certain motor vehicle crash characteristics compared with younger drivers. Adjusting for nighttime crash, high-speed crash, and seatbelt use, we calculated the odds of an older driver being killed or hospitalized compared with those of a younger driver. RESULTS: During the study years, there were 14,466 drivers older than 69 years and 68,706 drivers between the ages of 30 and 39 years involved in motor vehicle crashes in Utah. Older drivers were less likely to have crashes involving drug or alcohol use (odds ratio [OR] 0.1; 95% confidence interval [CI] 0.1 to 0.2) and less likely to have crashes at high speed (OR 0.6; 95% CI 0.6 to 0.7). Although older drivers were no more likely to have a crash involving a right-hand turn (OR 1.0; 95% CI 0.9 to 1.1) than younger drivers, they were over twice as likely to have a crash involving a left-hand turn (OR 2.3; 95% CI 2.2 to 2.5). Also, older drivers were more likely to be killed or hospitalized than younger drivers (OR, 3.5; P <.001). Among belted drivers, an older driver was nearly 7 times more likely to be killed or hospitalized than a younger driver (OR 6. 9; 95% CI 5.4 to 8.9). CONCLUSION: Older drivers do have distinctive motor vehicle crash patterns. Interventions must be taken to reduce the number of left-hand turn crashes involving older drivers. In addition, further research is needed to design, implement, and evaluate countermeasures that may enable older drivers to continue driving while keeping public safety in the forefront.

Accidents, Traffic↗

Physarum amoebae express a distinct fragmin-like actin-binding protein that controls in vitro phosphorylation of actin by the actin-fragmin kinase.

Amoebae and plasmodia constitute the two vegetative growth phases of the Myxomycete Physarum. In vitro and in vivo phosphorylation of actin in plasmodia is tightly controlled by fragmin P, a plasmodium-specific actin-binding protein that enables actin phosphorylation by the actin-fragmin kinase. We investigated whether amoebal actin is phosphorylated by this kinase, in spite of the lack of fragmin P. Strong actin phosphorylation was detected only following addition of recombinant actin-fragmin kinase to cell-free extracts of amoebae, suggesting that amoebae contain a protein with properties similar to plasmodial fragmin. We purified the complex between actin and this protein to homogeneity. Using an antibody that specifically recognizes phosphorylated actin, we demonstrate that Thr203 in actin can be phosphorylated in this complex. A full-length amoebal fragmin cDNA was cloned and the deduced amino acid sequence shows 65% identity with plasmodial fragmin. However, the fragmins are encoded by different genes. Northern blots using RNA from a developing Physarum strain demonstrate that this fragmin isoform (fragmin A) is not expressed in plasmodia. In situ localization showed that fragmin A is present mainly underneath the plasma membrane. Our results indicate that Physarum amoebae express a fragmin P-like isoform which shares the property of binding actin and converting the latter into a substrate for the actin-fragmin kinase.

Actins↗

Methylglyoxal causes swelling and activation of a volume-sensitive anion conductance in rat pancreatic beta-cells.

Membrane potential and whole-cell current were studied in rat pancreatic beta-cells using the 'perforated patch' technique and cell volume measured by a video-imaging method. Exposure of beta-cells to the alpha-ketoaldehyde methylglyoxal (1 mM) resulted in depolarization and electrical activity. In cells voltage-clamped at -70 mV, this effect was accompanied by the development of inward current noise. In voltage-pulse experiments, methylglyoxal activated an outwardly rectifying conductance which was virtually identical to the volume-sensitive anion conductance previously described in these cells. Two inhibitors of this conductance, 4,4'-dithiocyanatostilbene-2,2'-disulfonic acid (DIDS) and 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), also inhibited the depolarization and inward current evoked by methylglyoxal. Methylglyoxal increased beta-cell volume to a relative value of 1.33 after 10 min with a gradual return towards basal levels following withdrawal of the alpha-ketoaldehyde. None of the effects of methylglyoxal was observed in response to t-butylglyoxal which, unlike methylglyoxal, is a poor substrate for the glyoxalase pathway. Methylglyoxal had no apparent effect on beta-cell K+ channel activity. It is suggested that the metabolism of methylglyoxal to D-lactate causes beta-cell swelling and activation of the volume-sensitive anion channel, leading to depolarization. These findings could be relevant to the stimulatory action of D-glucose, the metabolism of which generates significant quantities of L-lactate.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Identification of three genes expressed primarily during development in Physarum polycephalum.

During the life cycle of Physarum polycephalum, uninucleate amoebae develop into multinucleate syncytial plasmodia. These two cell types differ greatly in cellular organisation, behaviour and gene expression. Classical genetic analysis has identified the mating-type gene, matA, as the key gene controlling the initiation of plasmodium development, but nothing is known about the molecular events controlled by matA. In order to identify genes involved in regulating plasmodium formation, we constructed a subtracted cDNA library from cells undergoing development. Three genes that have their highest levels of expression during plasmodium development were identified: redA, redB (regulated in development) and mynD (myosin). Both redA and redB are single-copy genes and are not members of gene families. Although redA has no significant sequence similarities to known genes, redB has sequence similarity to invertebrate sarcoplasmic calcium-binding proteins. The mynD gene is closely related to type II myosin heavy-chain genes from many organisms and is one of a family of type II myosin genes in P. polycephalum. Our results indicate that many more red genes remain to be identified, some of which may play key roles in controlling plasmodium formation.

Amino Acid Sequence↗

Distinctive emergency department usage for injury for workers' compensation cases in Utah in 1996.

To compare emergency department services paid by worker's compensation (WC) with services paid by other payers, a state database of 72,747 emergency department visits for injured adults (ages 21 to 54) in 1996 in Utah was analyzed. WC visits accounted for 21.6% (15,704) of all adult injury visits. The mean emergency department charge for WC visits was $282, and the admission rate was 17 per 1000 visits. The mean charge for other payers was $334, and the admission rate was 43 per 1000 visits. Differences were also found between these groups for Injury Severity Scores and diagnoses. In summary, WC emergency department usage was associated with less severe injuries than was emergency department usage for other payers in Utah in 1996.

Accidents, Occupational↗

The implications of protocol-based care on dental services in the military.

Downsizing, limited resources, and increasing costs provide challenges to the military health system. Variations in the diagnosis and treatment of dental disease add to the demands on the delivery system to provide access and ensure quality for uniformed personnel. Evidence-based dentistry is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. An evidence-based practice combines individual clinical expertise with the best external evidence available from systematic review of research findings. It provides a scientific basis for patient care, planning and implementation of health services, and development of health policy. Practice guidelines formulated on scientific evidence can reduce variations in the diagnosis and treatment of various dental conditions. A risk assessment protocol for treating dental caries can reduce operative dental treatment recommended at the initial examination and decrease the need for restorative care during a military career.

Clinical Protocols↗

Effects of methylglyoxal on rat pancreatic beta-cells.

The addition of the alpha-ketoaldehyde methylglyoxal (0.5 or 1 mmol/L) to single isolated rat pancreatic beta-cells caused a rapid, marked depolarization resulting in electrical activity. This effect of methylglyoxal on beta-cell was reversible upon removal of the alpha-ketoaldehyde, and could be inhibited by the anion channel blockers 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) and 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB). Methylglyoxal also resulted in elevated cytosolic [Ca2+] and an intracellular acidification in intact rat islets. In perifused islets, methylglyoxal provoked a modest, transient stimulation of secretion but inhibited glucose-induced insulin release. Incubation of islets with methylglyoxal resulted in the formation of large quantities of D-lactate, indicating metabolism of the alpha-ketoaldehyde via the glyoxalase pathway. The effects of methylglyoxal on beta-cell membrane potential, cytosolic [Ca2+] and intracellular pH were also observed in response to phenylglyoxal which is also effectively metabolized via the glyoxalase pathway. However, t-butylglyoxal which is poorly metabolized via the glyoxalase pathway, caused neither depolarization of the membrane potential nor intracellular acidification, but did inhibit glucose-induced insulin release. These findings suggests that the depolarization and acidification evoked by methyl- and phenylglyoxal are dependent upon their metabolism via the glyoxalase pathway. The possible mechanisms coupling alpha-ketoaldehyde metabolism via the glyoxalase pathway with membrane depolarization are discussed.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Modulation of bone morphogenetic protein-2 and bone morphogenetic protein-4 gene expression in osteoblastic cell lines.

Bone morphogenetic proteins (BMPs) belong to the transforming growth factor-beta (TGF-beta) superfamily and are crucial factors in the process of bone formation. Despite knowledge on their wide distribution and expression, however, there is very little information on the biological factors that affect gene transcription of these osteoinductive agents. To investigate this aspect of BMP gene regulation we have studied the effect of a number of factors known to affect osteogenic cells. Northern analysis showed modulation of the expression of BMP-2 and BMP-4 mRNAs in two human osteosarcoma cell lines, MG63 and Saos-2, by prostaglandin E2 (PGE2), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interferon-alpha (IFN-alpha), retinoic acid and 1,25(OH)2 vitamin D3. mRNA expressions of the normally used "housekeeping genes", glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and beta-actin, were found to be susceptible to influence by some of the factors used. Hence, an oligo(dT)15-18 probe was used to reliably estimate the relative quantities of mRNA present for normalization of data. In general, all factors down-regulated mRNA expressions of BMP-2 and BMP-4 in MG63 cells. IL-6 completely abolished detectable expression of BMP-2 mRNA, which was also greatly reduced by IL-1beta, retinoic acid and 1,25(OH)2 vitamin D3. PGE2 had similar influences on BMP-2 and BMP-4 expressions, showing reductions to approximately 60% of normal. In Saos-2 cells only 1,25(OH)2 vitamin D3 had any great effect on BMP-2 expression, which was down-regulated to approximately 60% of control values. BMP-4 was down-regulated by IFN-alpha (approximately 60%) and IL-1beta (approximately 20%). We conclude that BMPs are subject to regulation by a variety of factors and that this is dependent on the stage of the cell in the osteogenic lineage. Furthermore, the use of GAPDH and beta-actin genes as "housekeeping genes" in expression-modulation studies must be treated with care.

Actins↗