Routine perioperative pulmonary artery catheterization has no effect on rate of complications in vascular surgery: a meta-analysis.

Despite widespread use pulmonary artery catheterization has not been proven to reduce complications or mortality. One study supported the use of routine preoperative pulmonary artery catheterization in moderate-risk vascular surgery patients; several other studies have reported that pulmonary artery catheterization is not efficacious. Our goal was to scrutinize the data using meta-analysis. This is a systematic review of the literature. MEDLINE was searched for all articles on pulmonary artery catheterization, optimization, oxygen delivery, and preoperative preparation of vascular surgery patients. Data from papers judged appropriate for inclusion were analyzed using a computer program, Easy MA. Complications were defined as only those that could have reasonably have been prevented by or resulted from pulmonary artery catheterization. Of hundreds of possible papers only four were found to be adequate randomized prospective studies with similar exclusions, therapeutic endpoints, and interpretable complication and mortality rates. Controls included 174 patients versus 211 in the protocol group. Power analysis showed that the combined sample sizes were adequate. The meta-analysis demonstrates that the studies are homogeneous. The use of a pulmonary artery catheter does not prevent morbidity or mortality. Of the studies providing data on the amount of intravenous fluid administered three reported that statistically significantly more fluid was given to patients who underwent pulmonary artery catheterization. Meta-analysis indicates that in moderate-risk vascular surgery patients routine preoperative pulmonary artery catheterization is not associated with improved outcomes.

An unusual birthmark case thought to be linked to a person who had previously died.

The following case report describes a Burmese subject with an unusual birthmark and birth defects thought by local people to be linked to events surrounding the death of his mother's first husband. The nature of the link is explored, including how the assumption of a linkage could have led to subsequent events.

Life expectancy of major league baseball umpires.

UNLABELLED: Analysis of umpires' age at death suggests that fears regarding risks of their profession are unfounded. BACKGROUND: The on-field death 4 years ago of a veteran Major League Baseball (MLB) umpire raised questions regarding the mortality risks of this profession. OBJECTIVE: To determine if the life expectancy of MLB umpires differs from that of the general population. DESIGN: Ages of death of MLB umpires were determined, and the differences between the ages of death and age-adjusted life expectancies were calculated. T-score analysis was performed on these differences. Correlational analysis was also done on many different factors, including umpire debut year, debut age, life expectancy at debut, and length of career. RESULTS: No significant difference was found between the age at death of MLB umpires and their age-adjusted life expectancy. Correlational analyses showed that only length of career correlated with age at death. CONCLUSION: MLB umpiring is not associated with a shortened life expectancy. While this is most likely attributable to the profession having no inherent risk, it could also be explained by inherent risks being overcome by yet unidentified, unique factors.

Violence prevention: reaching adolescents with the message.

OBJECTIVE: To identify an effective medium for communicating with adolescents in a large-scale, cost-effective violence prevention program. METHODS: A set of youth violence prevention programs was established at The Stamford Hospital, a level II trauma center. The traveling version of the program was presented to middle school students in four parts: 1) a rap music video created by our violence prevention staff, 2) a facilitated discussion about dealing with anger, 3) a video of a trauma resuscitation in our emergency department, and 4) a commercial video of a teenage boy paralyzed after a gunshot wound. A written questionnaire with a five-point rating scale (1 to 5) was used to survey the audience 1 month after the program. The survey assessed the respondents' recall of each part of the program and the perceptions of the value of each part in identifying the problem of violence and reducing violent behavior. RESULTS: Of 99 respondents, the highest ratings for retention, problem identification, and impact were given to the commercial video (combined average category ranking of 11.394) and the rap music video (11.182). The trauma resuscitation video and the discussion of anger were ranked as being less effective (10.253 and 9.383, respectively). The audience seemed to comprehend the main point of the program and ranked the program, as a whole, higher than any of the parts when measured by success at problem identification and impact. CONCLUSION: Effective communication with adolescents is possible through many avenues. Children of the video age respond well to visual material. A violence prevention program should incorporate effective multimedia presentations. A variety of methods in combination proves to be most effective.

Hypothermia does not result in more complications after colon surgery.

Our objective was to determine the incidence of complications in postoperative patients who were either normothermic or hypothermic. A recent, widely publicized paper concluded that the maintenance of normothermia could reduce the incidence of infectious complications and shorten hospitalization in patients undergoing colorectal surgery. However, some controversy arose regarding the methods of this paper. Patients were deliberately rendered hypothermic, were given more than 3.5 days of prophylactic antibiotics and were transfused significantly more units of blood. We reviewed the charts of 150 consecutive patients who underwent elective partial or subtotal colectomy with primary anastomosis. Among the key items analyzed were intraoperative and postoperative temperature, use of warming devices, duration of surgery, transfusions, interval to oral intake and bowel function, length of stay, complications, infections, and laboratory values. Hypothermia was defined as intraoperative temperature <95.5 degrees F. There were 101 normothermic patients and 49 hypothermic patients. Hypothermic patients had a mean age of 68.7 years versus 66.8 for the normothermic patients (P = 0.472). Comorbidities were similar in both groups. Warming devices were used in >90 per cent of the patients in both groups. The rates of postoperative infections and complications were similar in both groups. Postoperative lengths of stay were also not different. Despite finding that one-third of our patients were hypothermic during elective colon resection, hypothermia had no effect on outcome variables. In contrast to the previous study, the incidence of infectious complications was identical in our patients. Before ascribing postoperative complications and increased resource utilization as adverse effects of hypothermia, further studies are indicated.

Using queueing theory to determine operating room staffing needs.

BACKGROUND: To meet American College of Surgeons criteria, Level I and II trauma centers are required to have in-house operating room (OR) staff 24 hours per day. According to the number of emergency cases occurring, hospitals may have varying needs for OR staffing during the night shift. Queueing theory, the analysis of historic data to provide optimal service while minimizing waiting, is an objective method of determining staffing needs during any time period. This study was done to determine the need to activate a backup OR team during the night shift at a designated, verified Level II trauma center. METHODS: The basic queueing theory formula for a single-phase, single-channel system was applied to patients needing the services of the OR. The mean arrival rate was determined by dividing the number of actual cases by 2,920 hours in a year (8 hours per night x 365). The mean service rate is determined by averaging the length of the actual cases during the period studied. Using the mean arrival rate and the mean service rate, the probability of two or more patients needing the OR at the same time was determined. This probability was used to reflect the likelihood of needing to activate the backup OR team. Simulation was then used to calculate the same probability and validate the results obtained from the queueing model. RESULTS: All OR cases (n = 62) beginning after 11 PM and before 7 AM from July 1, 1996, through June 30, 1997, were analyzed. During the study period, the average arrival rate (A) was one patient every 5.9 days (0.0212 patient every hour), with an average service rate (mu) of 80.79 minutes per patient (0.7427 patients per hour). According to queueing theory, lambda = 0.0212 patients per hour, mu = 0.7427 patients per hour, lambda/mu = 0.0285, the probability of no patients being in the system (P0) = 0.9714, P1 = 0.0278, P> or =2 = 1 - (0.0278 + 0.9714) = 0.0008. The probability of two or more cases occurring simultaneously on the night shift is less than 0.1%. CONCLUSION: In our institution, activation of a second OR team is unnecessary when the first team is busy with a case on the night shift because the likelihood of two cases occurring concurrently is less than one in a thousand. Queueing theory can be a valuable tool to use in determining the staffing needs of many hospital departments. Trauma centers should apply this mathematical model in optimizing the use of their operational resource.

Management of blunt splenic trauma in patients older than 55 years. Southern Connecticut Regional Trauma Quality Assurance Committee.

BACKGROUND: Many experts have suggested that blunt splenic trauma in patients older than 55 years should not be managed by observation because of supposed increased fragility of the spleen and decreased physiologic reserve in elderly patients. We sought to determine the outcome of nonoperative management of blunt splenic trauma in patients older than 55 years. METHODS: For the years 1994 through 1996, data for patients with splenic injury older than 55 years from seven trauma centers in a single state were reviewed. RESULTS: Blunt splenic trauma occurred in 41 patients older than 55 years. Eight patients were excluded from further analysis because of death from massive associated injuries within 24 hours of admission. The remaining 33 patients (mean age, 72+/-10 years) were divided into two groups: immediate exploration (10 patients) and observation (23 patients). Observation of blunt splenic injury failed in 4 of 23 patients (17%). No patient deaths were related to the method of management of the splenic injury. CONCLUSIONS: Observation of the elderly patient with blunt splenic trauma has an acceptable failure rate of 17%.

Effects of systemic resiniferatoxin treatment on substance P mRNA in rat dorsal root ganglia and substance P receptor mRNA in the spinal dorsal horn.

Capsaicin depletes the sensory neuropeptide substance P (SP) in the rat due to a combination of neuron loss and decreased synthesis in the surviving cells. Resiniferatoxin (RTX) mimics most, but not all, capsaicin actions. In the present study, the effects of RTX (300 microg/kg, s.c.) were examined on mRNA levels for SP and its receptor in the adult rat. The percentage of dorsal root ganglia (DRG) neuronal profiles showing an in situ hybridization signal for preprotachykinin mRNAs encoding SP was not altered following RTX treatment (up to 8 weeks), though the signal became perceptibly weaker. In accord, 2 weeks after RTX administration a 60% decrease was observed in the steady-state levels of SP-encoding mRNAs using Northern blot analysis, leaving the ratio of beta- and gamma-preprotachykinin mRNAs unchanged. No change was, however, observed in mRNA levels encoding tachykinins NK-1 receptors in the dorsal horn, the spinal targets for SP. The present findings suggest that RTX does not kill SP-positive DRG neurons, though it suppresses the synthesis of SP. Since RTX treatment does not alter NK-1 receptor expression, this reduced SP synthesis is likely to play a central role in the analgesic actions of RTX.

Cytoskeletal integration in a highly ordered sensory epithelium in the organ of Corti: reponse to loss of cell partners in the Bronx waltzer mouse.

This report is concerned with control of cell shaping, positioning, and cytoskeletal integration in a highly ordered cochlear neuroepithelium. It is largely based on investigations of events that occur during abnormal morphogenesis of the organ of Corti in the Bronx waltzer (bv/bv) mutant mouse. The organ's sensory hair cells and adjacent supporting cells ordinarily construct a spatially elaborate and supracellularly integrated cytoskeletal framework. Large microtubule bundles are connected to cytoskeletal components in neighbouring cells by actin-containing meshworks that link them to substantial arrays of adherens junctions. In bv/bv mice, degeneration and loss of most inner hair cells and outer pillar cells occurs during organ development. These cells flank each side of a row of inner pillar cells that respond by upregulating assembly of their actin-containing meshworks. This only occurs in surface regions where they no longer contact cell types involved in construction of the cytoskeletal framework. The meshworks are larger and exhibit a more extensive sub-surface deployment than is normally the case. Hence, assembly of intercellular cytoskeletal connecting components can proceed without contact with appropriate cell neighbours but termination of assembly is apparently subject to a negative feedback control triggered by successful completion of intercellular connection with the correct cell neighbours. In addition, inner pillar cells compensate for loss of cell neighbours by interdigitating and overlapping each other more extensively than is usually the case to increase opportunities for generating adherens junctions. Certain adherens junctions in the organs of +/+ and bv/bv mice exhibit features that distinguish them from all previously described cell junctions. The dense plaques on their cytoplasmic faces are composed of aligned ridges. We suggest that they are called ribbed adherens junctions. Perturbations of cell shaping and positioning indicate that loss of inner hair cells is the primary consequence of the bv mutation. Most of the other abnormalities can be understood in terms of a secondary sequence of morphogenetic aberrations (precipitated by loss of inner hair cells). These aberrations provide new information about the ways in which supporting cells help to control hair cell positioning.

Keratin filament deployment and cytoskeletal networking in a sensory epithelium that vibrates during hearing.

The intricate and spatially precise ways in which keratin intermediate filaments are deployed in certain cochlear epithelial cells, called supporting cells, suggests that these filaments make a micromechanically important contribution to the functional design of the guinea pig organ of Corti. Filament arrays that include keratins 8, 18, and 19 are confined mainly to regions close to the ends of large transcellular microtubule bundles in supporting cells. These cells and their microtubule bundles link sensory hair cells to a specialized basement membrane that vibrates during hearing. The keratin filament arrays apparently help anchor the ends of the microtubule bundles to cell surfaces. Filaments are concentrated at the apices and bases of most cells that contact hair cells. Substantial arrays of adherens junctions link the apices of these cells. Hence, keratin filaments may contribute to a cytoskeletal network that distributes mechanical forces from cell to cell and that coordinates the displacement of neighboring hair cells. However, high concentrations of keratin filaments have not been detected at the apices of one of the supporting cell types, which apparently has a mechanical role that is different from that of the others. Transmission electron microscopy has revealed previously undescribed filament networks at all the locations where the binding of antibodies to keratins is most marked. There is evidence that intercellular linkage of the keratin networks via their association with actin-containing meshworks and adherens junctions is more extensive than linkage provided by desmosomes.

Nucleation and capture of large cell surface-associated microtubule arrays that are not located near centrosomes in certain cochlear epithelial cells.

This report deals with the as yet undetermined issue of whether cell-surface associated microtubules in certain cochlear epithelial cells are centrosomally nucleated and subsequently migrate to microtubule-capturing sites located at the surface regions in question. Alternatively, the cells may possess additional nucleating sites which are noncentrosomal and surface-associated. These alternative possibilities have been investigated for highly polarised epithelial cells called supporting cells in the mouse and guinea pig organ of Corti using antibodies to pericentrin and gamma-tubulin. There is substantial evidence that both proteins are essential components of microtubule-nucleating sites in cells generally. Each mature supporting cell possesses a large microtubule array that is remotely located with respect to its centrosome (more than 10 microns away). The antibodies bind to a cell's centrosome. No binding has been detected at 2 other microtubule-organising centres that are associated with the ends of the centrosomally-remote microtubule array while it is being constructed. Such arrays include thousands of microtubules in some of the cell types that have been examined. If all a cell's microtubules are nucleated by its centrosome then the findings reported above imply that microtubules escape from the centrosomal nucleating site and migrate to a new location. Furthermore capture of the plus and minus ends of the errant microtubules is taking place because both ends of a centrosomally-remote microtubule array are attached to sites that are precisely positioned at certain cell surface locations. Minus ends are locating targets with an exactitude comparable to that which has been demonstrated for plus ends in certain cell types. These cells apparently operate a single control centre strategy for microtubule nucleation that is complemented by precise positioning of plus and minus end-capturing sites at the cell surface.

National health and medical services response to incidents of chemical and biological terrorism.

In response to the growing threat of terrorism with chemical and biological weapons, the US government has developed a national concept of operations for emergency health and medical services response. This capability was developed and tested for the first time during the Atlanta Olympic Games in the summer of 1996. In the event of a chemical or biological terrorist incident that exceeded local and state-level response capabilities, federal agencies would provide specialized teams and equipment to help manage the consequences of the attack and treat, decontaminate, and evacuate casualties. The US Congress has also established a Domestic Preparedness Program that provides for enhanced training of local first-responders and the formation of metropolitan medical strike teams in major cities around the country. While these national response capabilities are promising, their implementation to date has been problematic and their ultimate effectiveness is uncertain.

Lactone modulation of the gamma-aminobutyric acid A receptor: evidence for a positive modulatory site.

The gamma-aminobutyric acid-A (GABA(A)) receptor complex is allosterically modulated by a variety of substances, some of clinical importance. Barbiturates and neurosteroids augment GABA-currents and also directly gate the channel. A variety of gamma-butyrolactone analogues also modulate GABA-induced currents, with some potentiating and others inhibiting. Because several gamma-thiobutyrolactone analogues have biphasic effects on GABA currents, experiments with wild-type and picrotoxinin-insensitive GABA(A) receptors were performed to analyze whether some gamma-thiobutyrolactones interact with two distinguishable sites on the GABA(A) receptor. beta-Ethyl-beta-methyl-gamma-thiobutyrolactone inhibited GABA-induced currents at low concentrations (0.001-1 mM), but potentiated GABA-induced currents at higher concentrations (3-10 mM) in wild-type alpha1beta2gamma2-subunit containing ionophores. The related alpha-ethyl-alpha-methyl-gamma-thiobutyrolactone potentiated submaximal GABA currents in wild-type receptors at both low and high concentrations (0.1-10 mM). Mutations in the second transmembrane domain of alpha1, beta2, or gamma2 conferred picrotoxinin-insensitivity onto GABA(A) receptor complexes. When these mutated alpha1, beta2, or gamma2 subunits were incorporated into the receptor complex, beta-ethyl-beta-methyl-gamma-thiobutyrolactone potentiated GABA currents over the entire concentration range (0.1-10 mM). Neither the potentiating activity nor the EC50 of alpha-ethyl-alpha-methyl-gamma-thiobutyrolactone changed in the mutant receptors. Further studies demonstrated that the mutations did not affect the EC50 of chlordiazepoxide or phenobarbital. These and our earlier results identify a modulatory site on the GABA(A) receptor distinct from that interacting with barbiturates, benzodiazepines, and steroids. Additionally, they show that the gamma-butyrolactones probably interact at two different sites on the ionophore to produce opposite effects on GABA-mediated current.

Functional expression of a novel human neurokinin-3 receptor homolog that binds [3H]senktide and [125I-MePhe7]neurokinin B, and is responsive to tachykinin peptide agonists.

In 1992, Xie et al. identified a cDNA sequence in the expression cloning search for the kappa opioid receptor. When the cDNA was expressed in Cos-7 cells, binding of opioid compounds was observed to be of low affinity and without kappa, mu, or delta selectivity [Xie, G.-X., Miyajima, A. and Goldstein, A. (1992) Proc. Natl. Acad. Sci. USA 89, 4124-4128]. This cDNA was highly homologous to the human neurokinin-3 (NK-3) receptor sequence, and displayed lower homology to NK-1 and NK-2 sequences. This sequence was stably expressed in Chinese hamster ovary cells, which do not express neurokinin receptors naturally, and ligand binding and second messenger characteristics were compared with a human NK-3 receptor. The NK-3 receptor homolog bound [3H] senktide with a Kd of 39 nM, similar to that of the NK-3 receptor. The rank order of tachykinin peptides competing for [3H]senktide binding at the NK-3 receptor homolog was [MePhe7]neurokinin B > senktide > substance P = neurokinin A > neurokinin B. This cell line also bound [125I-MePhe7]neurokinin B; however, neurokinin B was an effective competitor. Tachykinin peptides stimulated both inositol phospholipid hydrolysis and arachidonic acid release at NK-3 and NK-3 receptor homolog cell lines, with similar rank orders of potency of [MePhe7] neurokinin B = neurokinin B = senktide > NKA = substance P. These results indicate that expression of the NK-3 receptor homolog cDNA in the Chinese hamster ovary cell system induces the expression of a receptor site with many similarities but certain key differences from that of the human NK-3 receptor. The results are discussed with reference to the existence of a novel human tachykinin receptor.

Centrosomal deployment of gamma-tubulin and pericentrin: evidence for a microtubule-nucleating domain and a minus-end docking domain in certain mouse epithelial cells.

This report provides evidence for two functionally and spatially distinct centrosomal domains in certain mouse cochlear epithelial cells. The vast majority of microtubules elongate from sites associated with the apical cell surface in these cells rather than from pericentriolar material surrounding the immediate environs of their apically situate centrioles. The distribution of gamma-tubulin and pericentrin at cell apices has been examined while microtubule nucleation is progressing because these centrosomal proteins are believed to be essential for microtubule nucleation. Antibodies to both proteins bind to pericentriolar regions but no binding has been detected at the apical cell surface-associated sites where the ends of thousands of recently nucleated microtubules are concentrated. Sparse transient microtubule populations can be detected between pericentriolar regions and surface sites while microtubule assembly advances. A procedure apparently operates in which the pericentriolar region functions as a microtubule-nucleating domain and the cell surface-associated sites operate as docking domains which capture the minus ends of microtubules that migrate to them shortly after nucleation. Docking domains may include some components of the pericentriolar material that have been relocated at the cell apex. A docking element hypothesis for centrosomal control of minus end positioning and dynamics in animal cells generally is proposed. This investigation has also shown that the concentration of gamma-tubulin and pericentrin around centrioles differs spatially and quantitatively in ways that are characteristic for the four cell types studied. Some of these characteristics can be related to differences in control of microtubule number and positioning.

Dual modulation of the gamma-aminobutyric acid type A receptor/ionophore by alkyl-substituted gamma-butyrolactones.

Alkyl-substituted gamma-butyrolactones (GBLs) and gamma-thiobutyrolactones exhibit convulsant or anticonvulsant activity, depending on the alkyl substituents. alpha-Substituted lactones with small alkyl substituents are anticonvulsant and potentiate gamma-aminobutyric acid (GABA)-mediated chloride currents, whereas beta-substituted compounds are usually convulsant and block GABAA currents. We have now found that this distinction is not so clear-cut, in that some compounds can both block and augment GABAA currents, but with different time courses. For example, alpha,alpha-diisopropyl-GBL (alpha-DIGBL) potentiates exogenous GABA currents in cultured rat hippocampal neurons but diminishes GABA-mediated inhibitory postsynaptic currents. A more detailed analysis demonstrates a triphasic effect of alpha-DIGBL on GABA currents, with a rapid inhibitory phase, a slower potentiating phase, and then an "off response" when the GABA/alpha-DIGBL perfusion is stopped. Thus, alpha-DIGBL can inhibit and potentiate GABA currents with kinetically different time courses. Inhibition is more rapid, but at steady state potentiation dominates. Using a simplified model of the GABAA receptor/ionophore, we have simulated our experimental observations with alpha-DIGBL. Another lactone, beta-ethyl-beta-methyl-gamma-thiobutyrolactone, also has dual actions, with inhibition predominating at low concentrations and potentiation predominating at high concentrations. We propose two distinct GBL modulatory sites on the GABAA receptor, i.e., an inhibitory "picrotoxin" site and an enhancing "lactone site." New information on the structure of the GABAA receptor/ionophore may allow the molecular dissection of these two sites.