Biomedical subjects

Maxwell M Krem

Publications and source records attributed to Maxwell M Krem.

6 recordsLinked to original sources

PubMed2005

Evaluation of the applicability, efficacy, and safety of a thromboembolic event prophylaxis guideline designed for quality improvement of the traumatically injured patient.

BACKGROUND: Thromboembolic events (TE) such as deep venous thrombosis (DVT) and pulmonary embolism (PE) are common after trauma. Our Trauma Practice Management Committee developed an evidence-based DVT/PE prophylaxis guideline using a modified Delphi approach to standardize care and reduce TE rates. Our objective was to evaluate the applicability, efficacy, and safety of this guideline in the traumatized patient, especially those admitted first to the intensive care unit (ICU). METHODS: We developed a risk-stratified DVT/PE prophylaxis guideline incorporating specific injuries, pertinent history, and physiologic parameters, favoring aggressive therapy in those at highest risk of dying from a PE. We prospectively collected data using this guideline in all patients admitted to the trauma or orthopedic-trauma services that were expected to stay for more than 48 hours (March-December 2003). Comparison was made with historical controls. Data collected included DVT, PE, prophylaxis level chosen, inferior vena cava filters, admission service and location, TRISS scores, length of stay, outcomes, adverse events, and specific risk factors. RESULTS: TE rates after implementation of the guideline were lower than historical controls for all patients (1.9% vs. 1.0%, p = 0.059) and for patients admitted first to the ICU (6.3% vs. 2%, p = 0.018). Completed sheets were collected for 46% of the targeted population. No bleeding events caused by guideline anticoagulation were noted, and one death occurred after inferior vena cava filter placement. Nine of the 12 TEs in the treatment group were in patients with spine or closed-head injury, delaying chemical prophylaxis. CONCLUSION: Form-based, risk-adjusted prophylaxis against TE leads to lower TE rates in a general and orthopedic ICU trauma population. Protocol compliance should be enforced.

Clinical Protocols↗

PubMed2004

Motor conversion disorders reviewed from a neuropsychiatric perspective.

BACKGROUND: Conversion disorder is a somatoform disorder defined by the presence of pseudoneurologic symptoms relating to voluntary sensory or motor function. The correct diagnosis of conversion disorder presenting with motor symptoms is complicated by the lack of gold-standard diagnostic tests and the absence of a universally accepted set of positive diagnostic criteria. This article reviews the epidemiology, pathophysiology, presentation, differential diagnosis, treatment, and prognosis of motor conversion, placing emphasis on diagnostic validity, reliability, and utility, while evaluating the empirical evidence supporting diagnostic and treatment strategies. DATA SOURCES AND STUDY SELECTION: Literature searches were carried out in PubMed using the keywords conversion disorder, motor conversion, dystonia, psychogenic, hysteria, somatization, motion disorder, movement disorder, and patho-physiology. Articles and book chapters in the author's personal collection were also utilized. CONCLUSIONS: Advances in neuropsychiatric research are leading to significant improvements in the diagnosis and understanding of motor conversion disorders. Positive, objective, and quantitative diagnostic criteria show significant promise for enhancing diagnostic accuracy. Current pathophysiologic research has begun to provide mechanistic explanations for conversion symptoms, thus blurring the distinction between psychogenic and organic motor disorders.

Cerebral Cortex↗

PubMed2003

Conserved Ser residues, the shutter region, and speciation in serpin evolution.

The suicide inhibitory mechanism of serine protease inhibitors of the serpin superfamily depends heavily on their structural flexibility, which is controlled in large part by the breach and shutter regions of the central Abeta-sheet. We examined codon usage by the highly conserved residues, Ser-53 and Ser-56, of the shutter region and found a TCN-AGY usage dichotomy for Ser-56 that remarkably is linked to the protostome-deuterostome split. Our results suggest that serpin evolution was driven by phylogenetic speciation and not pressure to fulfill new physiologic functions mitigating against coevolution with the family of serine proteases they inhibit.

Codon↗

PubMed2003

Dissecting substrate recognition by thrombin using the inactive mutant S195A.

The catalytically inactive mutant S195A was used to study the interaction of thrombin with substrates under equilibrium conditions. By monitoring changes in intrinsic fluorescence, we measured dissociation constants for a variety of synthetic substrates, PAR peptides and the inhibitor PPACK. The S195A mutant retains the Na(+)-binding properties of the wild type, and substrate binding to the mutant is enhanced by the presence of Na(+). Temperature dependence studies allowed calculation of the thermodynamic parameters of substrate binding at the active site and showed a negligible deltaC(p). Titration of synthetic substrates carrying substitutions at the P1-P3 positions revealed energetics consistent with the specificity hierarchy identified in hydrolysis by the wild type. Titration with PAR peptides, which interact with both the active site and exosite I of thrombin, also showed consistency with the results obtained with the wild type at steady state. These findings demonstrate that inactive mutants of enzymes make it possible to dissect the equilibrium components linked to substrate binding and complement information on the kinetic properties of the wild type.

Algorithms↗

PubMed2002

Ser(214) is crucial for substrate binding to serine proteases.

Highly conserved amino acids that form crucial structural elements of the catalytic apparatus can be used to account for the evolutionary history of serine proteases and the cascades into which they are organized. One such evolutionary marker in chymotrypsin-like proteases is Ser(214), located adjacent to the active site and forming part of the primary specificity pocket. Here we report the mutation of Ser(214) in thrombin to Ala, Thr, Cys, Asp, Glu, and Lys. None of the mutants seriously compromises active site catalytic function as measured by the kinetic parameter k(cat). However, the least conservative mutations result in large increases in K(m) because of lower rates of substrate diffusion into the active site. Therefore, the role of Ser(214) is to promote the productive formation of the enzyme-substrate complex. The S214C mutant is catalytically inactive, which suggests that during evolution the TCN-->AGY codon transitions for Ser(214) occurred through Thr intermediates.

Catalysis↗

PubMed2002

Evolution of enzyme cascades from embryonic development to blood coagulation.

Recent delineation of the serine protease cascade controlling dorsal-ventral patterning during Drosophila embryogenesis allows this cascade to be compared with those controlling clotting and complement in vertebrates and invertebrates. The identification of discrete markers of serine protease evolution has made it possible to reconstruct the probable chronology of enzyme evolution and to gain new insights into functional linkages among the cascades. Here, it is proposed that a single ancestral developmental/immunity cascade gave rise to the protostome and deuterostome developmental, clotting and complement cascades. Extensive similarities suggest that these cascades were built by adding enzymes from the bottom of the cascade up and from similar macromolecular building blocks.

Animals↗