Interaction of SecB with intermediates along the folding pathway of maltose-binding protein.

SecB, a molecular chaperone involved in protein export in Escherichia coli, displays the remarkable ability to selectively bind many different polypeptide ligands whose only common feature is that of being nonnative. The selectivity is explained in part by a kinetic partitioning between the folding of a polypeptide and its association with SecB. SecB has no affinity for native, stably folded polypeptides but interacts tightly with polypeptides that are nonnative. In order to better understand the nature of the binding, we have examined the interaction of SecB with intermediates along the folding pathway of maltose-binding protein. Taking advantage of forms of maltose-binding protein that are altered in their folding properties, we show that the first intermediate in folding, represented by the collapsed state, binds to SecB, and that the polypeptide remains active as a ligand until it crosses the final energy barrier to attain the native state.

Detection of beta-defensins secreted by human oral epithelial cells.

Human beta-defensins are antimicrobial peptides that may be critical in the innate immune response to infection. hBD1 and hBD2 are expressed in oral epithelial cells and are detected near the surface of oral tissue, consistent with a role in the epithelial protective barrier function. In this report, we examine secretion of beta-defensins in vitro and in biological fluid using ProteinChip(R) Array, surface enhanced laser desorption/ionization (SELDI) technology combined with time-of-flight mass spectrometry. We show that the 47-amino acid form of hBD1 and the 41-amino acid form of hBD2 are the major secreted forms. These forms are both expressed and secreted under conditions anticipated from previous analysis of beta-defensin mRNAs; specifically, hBD1 is detected in culture supernatant from both unstimulated and stimulated cells, and hBD2 is detected only in stimulated cells. Identity of hBD1 and hBD2 was confirmed by immunocapture on the ProteinChip surface. Both peptides are also present in gingival crevicular fluid that accumulates between the tissue and tooth surface, although hBD1 is also found in several smaller forms suggesting extracellular proteolysis. This methodology offers several technical advantages for detection of defensins in biological fluids, including ease and speed of screening, no need for HPLC preliminary processing, and small sample size.

Expanded microporous polytetrafluoroethylene as a vascular substitute: a two year follow-up.

Since 1974, 131 femoropopliteal, distal popliteal, and tibial bypasses have been performed using expanded microporous polytetrafluoroethylene (PTFE). Forty patients were operated on for limb salvage, and 21 had had previous bypass procedures. The overall patency rate was 82%. Early occlusions possibly were related to technical error, but most probably were due to severity of disease and poor runoff. Late occlusions were related to progressive atherosclerosis in the proximal or distal arterial tree. A 75.7% cumulative patency rate was noted at 28 months. In man the PTFE prosthesis demonstrates a smooth intimal lining with fibroblastic ingrowth into the interstices of the graft. These results are considered to be excellent in this high-risk patient population. The patency rates achieved with PTFE are better than those accomplished with alternative conduits and approach the patency rates reported with autogenous saphenous vein. Expanded microporous polytetrafluoroethylene with its high patency, pliability, and tissue incorporation is an excellent arterial substitute. Only with continued use of this material and a more uniform patient selection can more equitable comparisons be made between expanded PTFE and the autogenous vein.

Acute subdural hematoma: morbidity, mortality, and operative timing.

Traumatic acute subdural hematoma remains one of the most lethal of all head injuries. Since 1981, it has been strongly held that the critical factor in overall outcome from acute subdural hematoma is timing of operative intervention for clot removal; those operated on within 4 hours of injury may have mortality rates as low as 30% with functional survival rates as high as 65%. Data were reviewed for 1150 severely head-injured patients (Glasgow Coma Scale (GCS) scores 3 to 7) treated at a Level 1 trauma center between 1982 and 1987; 101 of these patients had acute subdural hematoma. Standard treatment protocol included aggressive prehospital resuscitation measures, rapid operative intervention, and aggressive postoperative control of intracranial pressure (ICP). The overall mortality rate was 66%, and 19% had functional recovery. The following variables statistically correlated (p less than 0.05) with outcome; motorcycle accident as a mechanism of injury, age over 65 years, admission GCS score of 3 or 4, and postoperative ICP greater than 45 mm Hg. The time from injury to operative evacuation of the acute subdural hematoma in regard to outcome morbidity and mortality was not statistically significant even when examined at hourly intervals although there were trends indicating that earlier surgery improved outcome. The findings of this study support the pathophysiological evidence that, in acute subdural hematoma, the extent of primary underlying brain injury is more important than the subdural clot itself in dictating outcome; therefore, the ability to control ICP is more critical to outcome than the absolute timing of subdural blood removal.

The financial impact of teaching surgical residents in the operating room.

BACKGROUND: There have been no published data regarding the cost of training surgical residents in the operating room. METHODS: At the University of Tennessee Medical Center-Knoxville, in addition to resident-performed teaching cases, some cases are performed without the assistance of residents by the same faculty. RESULTS: Sixty-two case categories involving 14,452 cases were compared for operative times alone. In 46 case categories (10,787 procedures), resident operative times were longer than faculty alone. In 16 case categories, resident operating times were shorter than faculty times. The net incremental operative time cost was 2,050 hours between July 1993 and March 1997. Assuming 4 years of operative training for 11 graduating chief residents, the cost per graduating resident was $47,970. CONCLUSION: Extrapolated to a national annual cost for the 1,014 general surgery residents who completed training in the 1997 academic year, the annual cost of training residents in the operating room is $53 million. This high monetary cost suggests the need for digital skills, selection criteria, the development of training curriculum and resource facilities, the pre-operating room need for suturing and stapling techniques, and perhaps the acquisition of virtual surgery training modules.

A bacteriologic study comparing closed suction and simple conduit drainage.

A simple experimental study was designed to determine if closed suction drainage reduces the migration of pathogenic bacteria along a drain tract. Sixty New Zealand rabbits, equally divided into three groups, were splenectomized through midline incisions. Group I served as the control group and received no drainage. Groups II and III had drainage of the splenic bed with simple latex conduit drains (Penrose drains) and closed suction drains (Jackson-Pratt drains), respectively. The skin near the drain exit site was inoculated with a Streptococcus organism. The animals were sacrificed after 72 hours, and intraperitoneal culture specimens were obtained. None of the control rabbits had positive cultures on intraperitoneal specimens. Eighteen of 20 rabbits (90 percent) in Group II (Penrose) had positive cultures on specimens from the splenic bed, whereas 75 percent had positive cultures on drain specimens. Only 4 of 20 (20 percent) of the Group III rabbits had positive cultures on the drain or splenic bed specimens. This difference was statistically significant by chi-square analysis (p less than 0.001). Retrograde migration of bacteria along a drain tract does occur with relatively high frequency with simple conduit drainage and is significantly less with closed suction drainage.

Critical analysis of open peritoneal lavage in blunt abdominal trauma.

Using the generally accepted paracentesis and lavage criteria for laparotomy for patients with blunt abdominal trauma, we found an accuracy rate of 97 percent but a nontherapeutic laparotomy rate of 27 percent. The 17 percent true false-positive rate of paracentesis and lavage is much higher than has been previously appreciated.

Blunt carotid injury: reassessing the role of anticoagulation.

Twenty patients with blunt mechanism injuries to the internal carotid artery were treated over a 10-year period. The purpose of this review is to assess the necessity and timing of anticoagulation as a primary therapeutic modality in patients with this injury. Sixteen patients (80%) survived, the majority with normal neurologic function. Twelve patients with either unilateral or bilateral carotid mural injury were anticoagulated. Ten survived with normal neurologic function. Five patients in the heparin anticoagulant group had a significant delay in the initiation of anticoagulation. All recovered without deficits. Two patients were treated with aspirin alone and recovered without deficits. Two patients received no treatment; one survived without deficits, and the nonsurvivor succumbed to a severe head injury. Therefore, a total of nine patients were either not treated with heparin or had a significant delay in the initiation of heparin. Eight of nine (88%) in this group recovered without deficit. A delay in the initiation of heparin therapy, no therapy, or the institution of antiplatelet therapy may all be appropriate in the initial management of mural injuries of the internal carotid artery.

Predictors of survival after inferior vena cava injuries.

In patients with inferior vena cava (IVC) injuries, predictors of survival are investigated. From 1987 to 1995, 27 IVC injuries were identified among 514 patients with vascular trauma. The ability of clinical determinants to predict survival were retrospectively assessed. IVC injuries occurred in 7 females and 20 males (mean age, 27.7 +/- 2.5 years) from both blunt (n = 14) and penetrating (n = 13) trauma. The mean revised trauma score was 10.2 +/- 0.6. Injuries were treated by primary repair (n = 22), ligation (n = 4), or prosthetic grafting (n = 1). Thirteen patients died (48%), 10 within 12 hours of admission. Suprahepatic (n = 2), retrohepatic (n = 12), suprarenal (n = 1), and infrarenal (n = 12) injuries were associated with 100, 67, 100, and 20 per cent mortality, respectively. Blood transfusions (16 +/- 4 vs 23 +/- 4 units), coagulation factor replacement (7 +/- 2 vs 7 +/- 2 units), and electrolyte solution use (8.6 +/- 1.4 vs 9.6 +/- 1.4 L) were similar among survivors and nonsurvivors. Four complications [venous hypertension (n = 2), IVC thrombosis (n = 1), and pulmonary embolus (n = 1)] occurred in the 14 survivors (28.6%). Blunt injury, revised trauma score, free perforation, injury location, intraoperative hypotension, and blood loss were predictive of mortality. IVC injuries remain extremely lethal, and improved survival is associated with infrarenal penetrating injuries and a contained hematoma.

Concomitant orthopedic and vascular injuries as predictors for limb loss in blunt lower extremity trauma.

Lower extremity trauma with concomitant orthopedic and vascular injury is associated with a high degree of limb loss. Despite successful arterial repair, many patients will ultimately require amputations. The effect of associated orthopedic injuries on limb loss in patients with lower extremity arterial injuries is investigated. From 1989 to 1994, 52 infrainguinal arterial injuries were identified among 365 vascular trauma patients. Clinical determinants were retrospectively assessed for the ability to predict postoperative amputations. Femoral artery injuries were present in 23 patients, with 53 per cent the result of blunt trauma. The incidence of lower extremity fractures was 53 per cent (60% open). Seventy-nine per cent of femoral artery injuries were repaired with saphenous vein grafts. Popliteal artery injuries were present in 13 patients, with 77 per cent the result of blunt trauma. The incidence of lower extremity fractures and posterior knee dislocations was 85 per cent (73% open) and 38 per cent, respectively. Ninety-two per cent of injuries were repaired with saphenous vein grafts. Tibial artery injuries were present in 16 patients, with 44 per cent the result of blunt trauma. The incidence of lower extremity fractures was 81 per cent (46% open). Twenty-five per cent of tibial artery injuries were treated with arterial repair, and 31 per cent with arterial ligation. Fourteen above-knee (AKA) and two below-knee amputations were performed. Amputation rates were 26.1 per cent (three AKAs) for femoral, 53.8 per cent (seven AKAs) for popliteal, and 38 per cent (four AKAs, two below-knee amputations) for tibial artery injuries. At the popliteal and femoral locations, greater than two long-bone fractures was predictive of amputation. For tibial arteries, one-vessel (n = 10), two-vessel (n = 3), and three-vessel (n = 3) injuries were associated with 20, 33, and 100 per cent amputations rates, respectively. Blunt injury, pulseless extremity, need for arterial repair (rather than ligation or no therapy), increasing number of injured tibial vessels, and multiple long-bone fractures were predictors of amputation (P < 0.05). Distal vascular injuries combined with complex orthopedic fractures are more likely to result in limb loss. Two or more long-bone fractures is predictive of amputation at all three locations.

The role of a substance abuse consultation team in a trauma center.

OBJECTIVE: Trauma is a leading cause of morbidity and mortality in the U.S., and substance abuse makes an enormous contribution to this problem as well as to the increased cost of health care. A substance abuse consultation (SAC) team was developed to evaluate and intervene with trauma victims who are suspected of having problems with alcohol and/or other drugs. This study was undertaken to determine the effectiveness of this service. METHOD: This study is a retrospective review of 100 consecutive trauma admissions who were felt to be at high risk for substance abuse and were referred to the SAC team for evaluation and intervention. This study was undertaken in a tertiary care teaching hospital in a cooperative effort between the trauma center and the addictions program. RESULTS: All 100 patients were diagnosed with psychoactive substance use disorders and 78 were referred for alcohol and other drug rehabilitation. Of these patients, 62% accepted a referral for drug and alcohol treatment. CONCLUSIONS: From these preliminary data, it appears that a SAC team may be effective in intervening with hospitalized trauma patients who have alcohol and other drug problems.

Hypothermic blood substitution enables resuscitation after hemorrhagic shock and 2 hours of cardiac arrest.

Uncontrollable hemorrhage accounts for a large proportion of total mortality in both civilian (31%) and military (47%) trauma victims. Hypothermia is a relatively safe method that could provide total body protection during hypovolemic shock and facilitate surgical intervention as a potentially life-saving procedure. This study tested the hypothesis that profound hypothermia and complete blood replacement in an established canine model, would facilitate resuscitative therapy from exsanguinating hypovolemic shock. Adult dogs were prepared for extracorporeal bypass using closed-chest peripheral cannulation under general anesthesia. Controlled hypotensive, hemorrhagic shock (mean arterial blood pressure < 50 mmHg) was induced for 30 min at normal temperature followed by temporary resuscitation using crystalloid infusion for approximately 10 min. Using our established procedure, the dogs were then cooled externally to 27 degrees C before initiating blood substitution with Hypothermosol (Cryomedical Sciences, Inc. Rockville, MD) via the extracorporeal pump. The heart was arrested during further cooling to below 10 degrees C and Hypothermosol was recirculated for 2 hr, with (3 dogs) or without (5 dogs) 1 hr of circulatory arrest. During rewarming the animals were autotransfused, weaned from the pump, and allowed to recover. All dogs (n = 8) survived, all but one with complete neurologic recovery: blood chemistry samples examined immediately after the procedure showed significant differences (p < 0.05) in only a few parameters, including creatine kinase (CK-BB and CK-MB), compared with the previous group of control dogs. The consistent survival of dogs showing apparently normal neurologic, physiologic, and biochemical recovery supports the concept that profound hypothermia using a protective hypothermic blood substitute could provide time for therapeutic resuscitation of currently intractable trauma cases.

Cardiac tamponade from central venous catheters. Report of a case and review of the English literature.

A case of acute cardiac tamponade caused by an internal jugular central venous catheter which was successfully treated is reported. The English literature is reviewed and shows that tamponade can occur up to 37 days after insertion and has a 65% mortality. The tamponade is usually caused by the actual infusate and not by blood.

Early tracheostomy in trauma patients.

A retrospective analysis of 118 trauma patients who underwent tracheostomy for airway and pulmonary management was undertaken. Timing of the procedure was defined as early (0-3 days), intermediate (4-7 days), and late (> 7 days). Head injury patients received tracheostomy early (p < 0.00003). Aspiration evaluated by modified bedside aspiration test was a frequent occurrence in all three groups with no difference in incidence (p < 0.34). Pneumonia was less frequent in the early group compared with the intermediate and late groups (p < 0.0034). The incidence of pneumonia in the early group was not different from that observed in early extubated patients (n = 282; p < 0.23). Our study suggests that early tracheostomy may decrease pulmonary septic complications in trauma patients. Although no change in length of stay can be attributed to the early performance of tracheostomy, preventing pneumonia in the intensive care unit setting with its resulting high expense is beneficial.

Filaroides hirthi in a dog: fatal hyperinfection suggestive of autoinfection.

Progressive dyspnea in a dog began 1 month after it had been hit by a car. Radiographs revealed diffuse interstitial and alveolar pneumonia. Large numbers of embryonated eggs were observed in bronchial washings; and many small nematodes, later identified as Filaroides hirthi, were found in the fine needle aspirates of pulmonary tissue. Numerous nematode larvae were demonstrated on fecal flotation. The severe hyperinfection strongly suggested autoinfection, probably associated with depressed immunologic competence due to chronic stress.

Sports-related abdominal trauma.

Athletes who sustain a direct blow to the abdomen that results in injury to spleen, liver, or kidney may have immediate severe pain and may become "shocky" quickly. Trainers, EMTs, paramedics, and team physicians should be aware of this possibility. In addition, athletes who have sustained direct blow and have had slower bleeding may collapse later either on the field, on the side-lines, or at home. They will be pale, sweaty, may complain of thirst, and the pulse will be rapid and thready. If a blow has been sustained that results in abdominal pain, the athlete should not be given liquids to drink. If he has collapsed or has diffuse abdominal pain he should be kept in a recumbent position, and the legs should be elevated in order to assist blood in returning to the heart (Trendelenberg position). If hypotensive shock is present, the PASG antishock garment should be applied. In cases in which there is serious concern about an intra-abdominal injury or the patient has collapsed in shock, transport to a hospital, preferably to a trauma center, should be effected as rapidly as possible. There should not be excessive delays in starting intravenous fluids or administering time-consuming procedures in the field. Truly serious intra-abdominal injuries as a result of nonvehicular sports-related incidents are not common. It is precisely for this reason that they are dangerous. Teammates, parents, trainers, coaches, EMTs, and paramedics are not accustomed to seeing them with any frequency. Because of this, the early signs of injury are often unrecognized, even in cases that progress to shock or collapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Medical care of the mentally retarded.

A physician providing medical services to a mentally retarded child must be prepared to deal not only with individuals who have multiple physical, mental and emotional problems, but also to help families' attempts to cope with an often bewildering array of service providers. The physician must know when to relate to the patient's needs on the basis of mental age and when to relate on the basis of chronological age; he must recognize the lifelong nature of the disability or disabilities with changing manifestations and needs as the individual grows older; he must be aware of the high incidence of certain types of associated problems or pathology in this population; and he must acknowledge, understand and overcome his own feelings of inadequacy, impatience and discomfort in dealing with the mentally retarded. The mentally retarded individual and his family must know where and how to obtain services; they must try to evaluate, hopefully with the guidance of concerned and knowledgeable physicians, which service need takes precedence at a particular time. They must keep in mind that routine medical care should not be neglected in the pursuit of specialty care, while, through it all, keeping things in their proper perspective.

Alcohol abuse among lesbians: a descriptive study.

Intensive interviews with 10 lesbian alcohol abusers revealed strong dependency needs, low self-esteem, and a high incidence of depression. Drinking increased power-related behaviors, enhanced self-esteem, and for many subjects increased feelings of depression. The findings suggest that lesbians with alcohol problems need (a) therapists who will accept their sexual orientation and (b) treatment that will help them increase their sense of power and self-esteem without alcohol.

Trauma radiology: an integrated approach.

A program at Allegheny General Hospital, Pittsburgh, integrated active radiologic participation with the services of the trauma team and emergency department. Two target areas served as objective criteria for the program's effectiveness: the time patients spent in the emergency department and the number of patients in whom vital diagnostic information was immediately obtained because of direct radiologic participation. This report outlines how the services were integrated and details our results in the two target areas studied.