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Acute neurosurgical emergencies are a potentially devastating occurrence requiring prompt evaluation and intervention by a neurosurgeon. Current consensus for acute subdural hematoma evacuation recommends a maximum time period of four hours from injury to operation; other injuries require prompt evaluation by a neurosurgeon but do not have soundly supported recommendations. Rural hospitals, such as Field Memorial Community Hospital in Centreville, MS, transfer acutely injured neurosurgical patients to centers with neurosurgical capability after initial stabilization. We report our experience with neurosurgical transfer patients and examine times from injury to arrival at neurosurgical care centers after being stabilized and transferred from Field Hospital.

Aims: In this review, we highlight the identification and analysis of molecules orchestrating dopamine (DA) signaling in the nematode Caenorhabditis elegans, focusing on recent characterizations of DA transporters and receptors., Methods: We illustrate the isolation and characterization of molecules important for C. elegans DA synthesis, packaging, reuptake and signaling and examine how mutations in these proteins are being exploited through in vitro and in vivo paradigms to yield novel insights of protein structure, DA signaling pathways and DA-supported behaviors., Results: DA signaling in the worm, as in man, arises by synaptic and nonsynaptic release from a small number of cells that exert modulatory control over a larger network underlying C. elegans behavior., Conclusions: The C. elegans model system offers unique opportunities to elucidate ill-defined pathways that support DA release, inactivation, and signaling in addition to clarifying mechanisms of DA-mediated behavioral plasticity. Further use of the model offers prospects for the identification of novel genes and proteins whose study may yield benefits for DA-supported neural disorders in man.

In previous studies examining the structural determinants of antidepressant and substrate recognition by serotonin transporters (SERTs), we identified Tyr-95 in transmembrane segment 1 (TM1) of human SERT as a major determinant of binding for several antagonists, including racemic citalopram ((RS)-CIT). Here we described a separate site in hSERT TM3 (Ile-172) that impacts (RS)-CIT recognition when switched to the corresponding Drosophila SERT residue (I172M). The hSERT I172M mutant displays a marked loss of inhibitor potency for multiple inhibitors such as (RS)-CIT, clomipramine, RTI-55, fluoxetine, cocaine, nisoxetine, mazindol, and nomifensine, whereas recognition of substrates, including serotonin and 3,4-methylenedioxymethamphetamine, is unaffected. Selectivity for antagonist interactions is evident with this substitution because the potencies of the antidepressants tianeptine and paroxetine are unchanged. Reduced cocaine analog recognition was verified in photoaffinity labeling studies using [(125)I]MFZ 2-24. In contrast to the I172M substitution, other substitutions at this position significantly affected substrate recognition and/or transport activity. Additionally, the mouse mutation (mSERT I172M) exhibits similar selective changes in inhibitor potency. Unlike hSERT or mSERT, analogous substitutions in mouse dopamine transporter (V152M) or human norepinephrine transporter (V148M) result in transporters that bind substrate but are deficient in the subsequent translocation of the substrate. A double mutant hSERT Y95F/I172M had a synergistic impact on (RS)-CIT recognition ( approximately 10,000-fold decrease in (RS)-CIT potency) in the context of normal serotonin recognition. The less active enantiomer (R)-CIT responded to the I172M substitution like (S)-CIT but was relatively insensitive to the Y95F substitution and did not display a synergistic loss at Y95F/I172M. An hSERT mutant with single cysteine substitutions in TM1 and TM3 resulted in formation of a high affinity cadmium metal coordination site, suggesting proximity of these domains in the tertiary structure of SERT. These studies provided evidence for distinct binding sites coordinating SERT antagonists and revealed a close interaction between TM1 and TM3 differentially targeted by stereoisomers of CIT.

Bone plate design has evolved dramatically in recent years. The Dynamic Compression Plate (DCP) has been superseded by bi- and uni-cortical plates that claim a reduced interface contact between the plate and the underlying bone. It is believed that contact reduction ameliorates the localised ischaemia that develops subsequent to plate application. In this study, the interface characteristics of the Limited Contact-Dynamic Compression Plate (LC-DCP) and the Contour Plus (CP) plating systems have been quantitated using Fuji prescale pressure sensitive film interposed between the plate and the bone. Ten-hole plates were applied to the same aspect of either the humeral, radial or ulnar diaphysis of human cadaveric bone in a reproducible manner. The average pressure, force and interface contact area were calculated using Interactive Data Language (IDL) image analysis software. The CP system was consistently lower, in terms of interface contact, than the LC-DCP in each of the specimen locations tested (P<0.0001). The CP system displayed a 'point-contact' configuration along the interface with high pressures recorded at these points, the significance of which is unknown.

Selection of an appropriate suture requires a knowledge of many factors. These include its mechanical characteristics, its durability, the period of mechanical effectiveness and the tissue reactivity to the material. Absorbable suture materials were incubated in synovial fluid or phosphate buffered saline, at 37 degrees C, for periods up to 12 weeks. Mechanical testing was performed to determine the yield strength, percentage elongation and stiffness of each material in response to incubation. Significant differences were observed in response to time of incubation, material size ('0' or '2-0'), incubation medium and material properties (P < 0.001). Based on the results obtained Vicryl and PDS appear ideal for short-term and medium term apposition, respectively. Panacryl has more durable mechanical features and may well be suited to long-term tissue apposition, such as tendon repair or arthroplasty.

Rupture of the biceps tendon occurs predominantly in the middle-aged and elderly, being predisposed through bicipital tendinitis and rotator cuff lesions. Surgical repair may be an option for those requiring strength in supination. This study compared the initial fixation strength of keyhole tenodesis (n = 7) and interference screw fixation by use of cadaveric specimens. Two interference screws were evaluated (n = 7 x 2): the round-headed cannulated interference screw (RCI) and a bioresorbable screw (Sysorb). All specimens failed at the fixation site but one. This study found that overall there was a significant effect as a result of study group (keyhole vs Sysorb vs RCI, P =.034). The post hoc comparisons revealed that the keyhole was significantly stronger than the RCI screw (P =.033) but not significantly different compared with the Sysorb screw (P =.129). No significant difference was observed between the Sysorb and RCI screws (P =.762). Interference screw fixation failed by tendon slippage at the screw-tendon-bone interface; keyhole fixation failed by tendon splitting and slippage out of the restraining keyhole. Keyhole tenodesis may permit earlier postoperative mobilization when compared with tenodesis by use of interference screw fixation.

An ovine model of anterior cruciate ligament reconstruction was utilized to evaluate the biomechanical and histological response of a polylactic acid tibial fixation staple (Gunze Ltd., Japan/Zimmer, Japan). This was performed in a comparison with metallic staples, currently utilized for this procedure. The prosthesis consisted of autograft combined with a Leeds-Keio (L-K) ligament. Early post-operative mobilization was followed by retrieval of specimens at 6, 12 and 24 weeks post-reconstruction. Evaluation of the mechanical characteristics of the graft reconstructions (tensile strength) showed no significant differences (P>0.05) between the staple types for each time period. The histological response to the polylactic acid staple was minimal over the time period studied, with no adverse tissue reactions observed. The mode of reconstruction failure was observed to change with time (P<0.05) presumably as the graft characteristics alter. Overall the absorbable staples performed at a comparable level with the metallic staples within the scope of the study.

The evolution of bone plate design has been with a view to reducing the interface contact between the plate and the underlying bone thereby limiting the perfusion deficiency that develops. Little consequence, however, has been attributed to the drilling of holes in the steps prior to bone plate application; the work present herein attempts to define the vascular response of bone to the trauma of drilling holes. Anaesthetized sheep underwent the creation of drill holes in both tibiae and metatarsi. Animals were then heparinized and euthanatized. Utilizing femoral cannula, perfusion of the vasculature ensued; spalteholz (India ink), disulphine blue and radiocontrast material (barium sulfate). Decalcified histology was performed and correlated with the perfusion studies. Regions of perfusion deficiency were observed immediately adjacent to, and removed from, the drill hole site. Radiographic images showed substantial haematoma formation and vascular disruption in the vicinity of the drill hole site. Histologically, blood vessels immediately adjacent and distal to the drill hole site, contained a proteinaceous/cellular material occluding the vascular space. Our findings support the proposal of a short-term obstruction in cortical blood flow which may contribute to later adaptational osteopaenia following bone plate application. We have observed an acute vascular insufficiency in cortical bone directly related to the trauma of drilling screw holes.

A single, complete, ovine knee was imaged using conventional MRI then dissected allowing comprehensive dimensional measurement of the intra-articular structures. A three-dimensional (3-D) computer model of the knee was generated from the MR sections. Thirty-two individual structural measures were recorded from the image output for which there was an available surgical measure for direct comparison. The results of Pearson's correlation testing show a rounded score of 1.00, suggesting an exceptional linear correlation between direct anatomical measurement and the 3-D image output. Further analysis of the data revealed an average error of measurement of 0.2mm across the 32 measures. The findings of this preliminary study suggest that 3-D reconstruction from MR data may be an appropriate, and accurate, means for making dimensional measurements of the bony and soft tissue structures of the ovine knee. It is unlikely that the measurement error would be of any great clinical significance. There is evidence in the literature to suggest that an ovine knee may be considered an acceptable model for substitution for the human knee in diagnostic assessment studies. Therefore, such findings may be considered clinically relevant in the field of human knee assessment.

The acute vascular response in bone to surgical trauma was investigated utilizing a sheep model. Blood flow and distribution were determined using two methods; perfusion of the vasculature with an intravascular vital dye (Disulphine blue) prior to euthanasia and by radionuclide angiography (RNA) before and after each surgical intervention. The pattern of Disulphine blue distribution provided a good indication of local perfusion and response to surgical trauma (drilling holes). Radionuclide angiography provided a dynamic image of the vascular response to surgical trauma. The generation of time activity curves of the first pass of radionuclide bolus enabled calculation of the relative blood flow through selected regions. For both techniques areas of ischaemia were apparent which were directly related to the location of screw holes. We conclude that factors other than bone plate contact influence the ischaemia that develops in bone subsequent to the application of bone plates.

Biological fracture repair is becoming an increasingly popular means of fracture fixation. This technique involves a reduction in the amount of surgical trauma thereby preserving vascular supply and soft-tissue integrity combined with the implantation of less hardware. The aim is the stimulation of callus formation as the means by which fracture union occurs. This paper describes the mechanical effect of the symmetrical omission of screws on construction stiffness and bone surface strain following the application of bone plates to cadaveric bone. The influence of the pattern of screw omission was evaluated in both intact and osteotomized bone specimens. The application of bone plates using certain patterns of screw omission did not significantly effect the stiffness of the final construction whilst inherent bone surface strain was increased. It was concluded that the omission of screws in certain defined patterns for a given plate-bone construction may meet the criteria for 'biological fixation'. There was no apparent deleterious effect on structural stiffness following the omission of 40% of the total screw complement from a plate-bone construction.

Using Fuji Prescale Pressure Sensitive Film we evaluated the influence of screw torque, object radius of curvature, mode of bone plate application (compression or neutral loading) and bone plate design on bone-plate interface mechanics. Testing was performed using 4.5 mm and 3.5 mm dynamic compression (DC) (stainless steel) and limited contact-dynamic compression (LC-DC) plates (titanium). Plexiglass tubing, having different radii of curvature, was used to simulate bone but having more uniform geometric and structural properties. With the film interposed between the bone plate and the plexiglass, bone plates were applied at predetermined levels of screw torque. The resultant image was digitized and then underwent computer-assisted analysis to yield the interface contact area (%) and the average force (in Newtons N) between the bone plate and the object to which it was applied. In any given object, screw torque had the most significant influence on both interface contact area (P = 0.0001) and average force (P = 0.0001) at the interface. The bone plates responded differently to dynamization. The DC plate, when applied in compression loading mode, was lifted off the object between the two central screws when compared to the same plate applied in neutral loading mode (P = 0.0001). Conversely, in the LC-DC plate, an increase in the overall interface contact area was observed when applied in compression loading mode (P = 0.0002). At a given level of applied screw torque, the object radius of curvature appeared to be a major determining factor for interface contact area and average force (P = 0.0001, P = 0.0001). We conclude that variables other than bone plate design also influence the interface contact area and average force between a bone plate and object to which it is applied.

Objectives: To determine the effects of bone morphology on the interfacial mechanics of bone plate fixation., Design: A comparison of two bone plate designs using measures of contact area and force in three conditions of bone type., Intervention: The influence of bone plate design, bone type, and implant location on interfacial characteristics of contact area and average force were evaluated using pressure-sensitive film in cadaveric bone. Data were quantitated using computer-assisted image analysis., Main Outcome Measurements: Means of the two dependent variables in each of the three conditions were compared using analysis of variance., Results: In human femora and equine third metacarpi, there were no apparent differences in interface contact area attributed to bone plate design, although there were significant differences for interface contact force. In humeri, significant differences in both interface contact area and force were found between bone plate designs., Conclusions: Results show that bone surface topography and implant location are major determinants of the interfacial elements of contact area and average force between a plate and the bone to which it is applied.

From 1957-1990 four patients underwent total abdominal colectomy with primary ileoproctostomy for control of massive lower gastrointestinal hemorrhage at Field Memorial Community Hospital in the rural community of Centreville, Mississippi. Surgery was performed emergently in two cases, and urgent/electively in the two remaining cases. Bleeding was controlled in each case. Upper Gastrointestinal and rectal bleeding were excluded, but further attempts to localize bleeding were not performed due to the difficulty of obtaining these studies at our hospital and the questionable likelihood of localizing the bleeding site. Many authors recommend an aggressive diagnostic workup including radio-labeled RBC scintigraphy and mesenteric angiography to localize colonic bleeding. Their aim is to perform a directed colonic resection for control of bleeding. However, most authors support total abdominal colectomy in cases where 1) hemodynamic instability does not allow extensive preoperative evaluation 2) there is a recurrent bleeding 3) more than one site is visualized as bleeding 4) there is widespread diverticulosis in a good-risk patient or 5) diagnostic procedures are unavailable. The low morbidity and good bowel function achieved following total abdominal colectomy, combined with the unavailability of diagnostic radiographic studies leads us to recommend total abdominal colectomy for control of massive lower gastrointestinal bleeding. The mortality of the procedure can be minimized by operating in a timely manner, prior to 10 units transfusion or 4 units within 24 hours, or operating in cases of recurrent bleeding.

Obesity is a public health issue of major concern for the United States and other developed nations. In the last several decades, bariatric surgery has developed as a means of treating morbid obesity. Vertical banded gastroplasty (VBG) is an attractive procedure because it has fewer side effects than other forms of bariatric surgery and maintains physiological continuity of the gut. VBG was performed in 36 patients at a rural community hospital from 1982-1990. There was only one intraoperative complication necessitating splenectomy and two early postoperative complications--gastric leak and marginal stress ulcer--necessitating reexploration. Twenty-five patients were available for follow-up, at which time they were an average of 6.4 years out of surgery. Two of these patients had died, both from cardiac arrest months or years after VBG. The remainder had gone from a preoperative average of 86.7% over ideal weight according to 1983 Metropolitan Life insurance Tables to 54.5% over ideal weight. Mean BMI for this group had changed from 41.2 preoperatively to 34.7 at follow-up. Success was defined as weight loss to < 60% over ideal or BMI < 35, removing the individual from the morbidly obese category. According to this criteria, VBG provided successful weight loss in 72% of subjects in the follow-up group. Weight loss results may have been biased as a significant number of patients were lost to follow-up and may have constituted failures. In general, most individuals did not make concomitant changes in diet or sedentary life-style which would have supported weight loss effected by VBG. Moreover, regain of weight was progressive and possibly inexorable. Nearly all individuals nonetheless reported great satisfaction with their surgery. VBG is a viable option in the treatment of morbid obesity, but criteria for success needs to be better defined in order to determine whether the procedure is "worth it."

Blunt carotid dissection (BCD) is a rare injury occurring in less than one in 1,000 victims of blunt injuries. Using a 4-year experience in a trauma system with 14 cases of BCD, we performed a matched blunt trauma patient case-control analysis to determine if there were patterns of injuries that were associated with increased risk of BCD. Patients with combinations of head, facial, and cervical spine injuries with or without extremity fractures proved to be at significantly increased risk for BCD. Duplex scanning appears to be a useful screening tool for these patients. Anticoagulation was the preferred treatment once neurologic deficits were present.

Clinical Competencies of new graduates from baccalaureate programs have periodically been criticized by employers of new graduates. In an effort to understand the levels of clinical preparation for new baccalaureate graduates, three hypotheses dealing with the cognitive, affective, and psychomotor domains were tested. A review of the literature reveals that most exploration and work has been done relative to the cognitive domain. Sixty-four NLN accredited baccalaureate programs responded to a request that they provide all of the clinical objectives used in their program. Findings revealed that there were clinical evaluation criteria written at all levels of the three domains; however, most schools did not have objectives at each of the levels of the three domains. A disproportionately large number of clinical objectives are written at the cognitive domain. The study raises the question as to the abilities of students to be clinically proficient upon graduation when there are relatively few evaluation criteria written in the psychomotor domain.

The existence of an innate insulin insensitivity in ponies was investigated and compared with the situation in larger breeds of horse. Ponies that were fat or had previously suffered laminitis were found to be far more intolerant to oral glucose loading (1 g/kg bodyweight [bwt]) than normal ponies or Standardbreds. These ponies also exhibited a far greater response in plasma insulin levels after glucose loading. Insulin response tests (0.4 iu/kg bwt insulin intravenously) showed only a minimal and very protracted response in both the fat and laminitic groups. The relevance of these findings in regulation of carbohydrate and lipid metabolism, and their role in the pathogenesis of hyperlipaemia, are discussed.

Laminitis is an important condition in horses and ponies, not just because of the seriousness of the clinical signs and systemic changes involved, but because of the potentially poor prognosis and likelihood of recurrence. Laminitis is particularly prevalent in ponies and involves a multiplicity of aetiological factors. Fat ponies and those having previously suffered laminitis were found to be far more intolerant to oral glucose loading (1 g/kg bwt) than normal ponies or Standardbred horses. These ponies also exhibited a far greater response in plasma insulin levels after glucose loading. Insulin response tests (0.4 iu/kg bwt insulin intravenously) showed only a minimal and very protracted response in both the fat and laminitic ponies establishing the existence of an apparently innate insulin insensitivity in these animals. These findings are important in regulation of carbohydrate and lipid metabolism and play a role in the pathogenesis of laminitis. The reduction of insulin effectiveness leads to elevation in thromboxane A2 activity, predisposing the animal to peripheral vasoconstriction, compromisation of blood flow to the foot and the development of laminitis.

This newly developed stress-management program evolved from study of the three major trends in stress research: psychological, physiological and sociological. Primarily geared to managers in an industrial setting, this program helps the individuals to reduce physiological tension via autohypnosis and alter stress-producing behaviors through a number of cognitive restructuring techniques. A variety of philosophical issues are raised that relate to 'type A' behavior focusing on 'the hurry syndrome', aggression and a general balance in 'life tasks'. In addition, there is an educational component and participants are acquainted with their 'health probabilities' in terms of life style, weight, smoking and other factors. This multimodal program follows participants over a 2-year period to reinforce psycho-behavioral changes.

In September and October 1986, seven patients were burned in beach fires in San Diego County; this prompted us to review our past patients who suffered beach-fire burns. A review of our registry revealed an additional 15 patients who had been burned in beach fires in the past 2 years. Four such cases are summarized, and common features are described.

Studies have been conducted to characterize phenotypic and functional characteristics of murine and human cells after burn injury. The detailed analysis of T-cell distribution in the burned mouse, and the analysis of activation markers L3T4/Lyt-2 and Ia, reveals characteristic changes including the presence of "activated" suppressor cells during post-injury suppression. Studies of humoral markers suggest an increased production of IgG in burned animals upon sheep red blood cells (SRBC) challenge, accompanied by increased clearance or catabolism of serum antibody, which results in depressed serum levels. Finally, in vitro phagocytosis studies using fluorescein isothiocyanate (FITC)-labeled killed bacteria reveal that burn patient sera are clearly defective in their ability to promote opsonization of one or more specific organisms by neutrophils. The addition of exogenous IgG to the incubation medium improves this response, suggesting that postburn phagocytic depression is an opsonic defect, rather than an inhibitory effect of burn serum on neutrophils.

We performed detailed phenotypic analysis of murine lymphocytes from thymus, spleen, lymph node, and peripheral blood using commercially available monoclonal antibodies, each with specificities for membrane surface markers and dual-color flow cytometry. Erythrocyte lysis techniques were utilized for lymphocyte preparation so that inherent difficulties with gradient techniques would be avoided, such as the potential for loss of abnormally sized cells. These studies demonstrated that the specificities of each monoclonal must be carefully determined; for example, the Lyt-1 monoclonal, frequently utilized to identify helper/inducer T cells, also reacts with suppressor/cytotoxic (Lyt-2+) cells; helper/inducer cells are better studied with a more recently available monoclonal, L3T4. Cells from different tissues may differ greatly not only in the presence of surface markers, but also in the surface density of each marker; this density can be studied and quantitated using appropriate analytic software. We also show that larger and more granular lymphocytes appear to be enriched for surface Ia antigen, indicating that these cells may be activated or regulatory subsets; these large, Ia+ T-cells will be lost from analysis if standard, narrow gate settings are used for analyzing forward and side-scatter characteristics or for cell sorting.

We have performed simultaneous compartmental pressure monitoring in 14 burned extremities using both the established wick catheter and the recently developed fibreoptic catheter system. Initial pressures recorded by both systems correlated well. Discrepancies in subsequent values were considered to be either due to improper limb positioning or because of catheter damage or obstruction. Both systems are position sensitive, but the problem can be minimized by careful anchoring of the catheters. The fibreoptic catheter is more fragile, but the wick catheter, despite a constant slow infusion of heparinized fluid, is liable to obstruct. While it has proven difficult to compare cost-effectiveness for the two systems, it is our impression that the fibreoptic system offers advantages in terms of ease of placement and maintenance and long-term reliability of measurements. Experience from other burn groups with the two systems will be important. Finally, the parallel use of the two catheters emphasizes the potential fallibility of either system, and the necessity of applying clinical judgement in evaluating circumferentially burned extremities even though direct pressure monitoring is employed.

Hyperlipaemia is an important condition in ponies, not just because of the seriousness of the clinical signs and biochemical changes involved, but because of the distress it causes owners and breeders that have had animals suffer from it. Hyperlipaemia occurs most commonly in fat ponies in late pregnancy and is rarely seen in larger horses. The syndrome has similarities with conditions in other species but the definitive aetiologies are not yet known. The condition in ponies is undoubtedly related to stress. The biochemical mechanisms involved in equine hyperlipaemia are considered and an hypothesis of possible pathogenesis is put forward. This hypothesis is tested by presenting the results of a preliminary study to evaluate glucose and lipid metabolism in horses and ponies. It appears that the pony is markedly insensitive to insulin compared to larger horses which means that triglycerides are more readily mobilised and the animal is therefore susceptible to hyperlipaemia in a situation of negative energy balance. The effect of stress is to increase cortisol levels which only exacerbates the insulin insensitivity and so creates a vicious circle. The importance of an innate insulin insensitivity may also be important in the pathogenesis of such conditions as laminitis.

We present a case of extensive cutaneous chemical burns from sulfuric acid in a baby girl. The patient's age and the appearance of her wounds made it difficult to judge the depth of the wounds in the early stages of care. Because of the uniform appearance of the wounds and the large areas of injury, tangential excision was considered but delayed; the wounds were monitored with serial histologic biopsies for assessment of depth and progression of healing. The presence of viable dermal tissue and adnexal structures on histologic examination encouraged a program of observation and local wound care, which led to progressive healing of the wounds in 18 days. Histologic monitoring of the wounds proved to be a helpful adjunct in the clinical management of this difficult case.

We describe a severe case of warfarin-induced skin necrosis with extensive full-thickness tissue loss involving approximately 12 per cent of the body surface area. The early management was conservative, with wound observation only, and no aggressive débridement was attempted. Wound and associated systemic sepsis followed, and the patient was transferred to our burn unit. The wounds were then managed with aggressive therapy including surgical excision, temporary coverage with allograft, and final closure with split-thickness autograft. This case illustrates important principles of appropriate surgical management of extensive skin lesions of this type.