Stereotactic breast biopsy: a study of first core samples.

Stereotactic core needle biopsy (SCNB) is a sensitive and specific indicator of breast pathology. Commonly the first biopsy core is taken from the center of the lesion in question. Multiple cores are then taken from points peripheral to the central core. The sensitivity and specificity of the central core to diagnose breast disease is unclear. We compared the pathology of the central core biopsy with that of the remaining cores in a prospective study to determine the sensitivity and specificity of the central core to diagnose breast disease. All patients undergoing SCNB for breast lesions in a single surgical office during a 7-month period were eligible for inclusion. One hundred thirty-three patients with first cores from 145 biopsy sites were included. The histologic diagnosis from 117 (81%) of the first cores from these 145 biopsy sites were representative of their respective samples as a whole. Seventy-seven (53%) of the first cores were in complete agreement with the final histologic diagnosis whereas 40 (28%) had minor differences with the histologic diagnosis that had little or no clinical significance. Twenty-eight (19%) central core samples did not agree with the final pathologic diagnosis. Seven of these 28 patients each had a final diagnosis of cancer missed by the central core biopsy. The first core sample had a sensitivity for cancer detection of 79 per cent and specificity 100 per cent. SCNB remains a sensitive and specific identifier of breast pathology. When mammographic evidence of calcifications was the primary indication for SCNB (n = 75) calcification was present in the central core in 51 (68%). In these 51 patients the central core biopsy was in agreement with the final histologic diagnosis in 46 (90%) specimens. Histologic review of the first core sample alone lends no increased benefits and in fact misrepresents the pathology present in a significant number of patients. When analyzed as an independent predictor of breast pathology the first core is a more sensitive indicator than subsequent individual cores, but the most accurate predictor of pathology is examination of the entire group of core samples. This study confirms the need for acquisition of multiple cores from each lesion in question.

Twelve-year experience with the Thow long intestinal tube: a means of preventing postoperative bowel obstruction.

The purpose of this study was to determine the effectiveness of the Thow long intestinal tube (LIT) for prevention of postoperative adhesive small bowel obstruction (ASBO) and to compare the Thow tube with other LITs. The charts of all patients who had placement of a Thow tube between January 1986 and November 1998 were reviewed. Thirty-four patients ranging in age from 9 to 86 years (mean 57.9) were included in the study. Twenty-five were contacted by phone for long-term follow-up. Twenty-nine patients had undergone previous abdominal surgery, and in 11 of 29 the previous surgery was for ASBO. Indications for surgery and Thow tube placement included: bowel obstruction (25), perforated viscus (five), carcinomatosis (two), colitis (one), and atonic bowel (one). Review of the operative notes revealed no difficulty in advancing the Thow tube in 32 of 34 patients (94%). Thow tube-related complications occurred in nine patients (25%). All complications were associated with the gastrostomy site, and only one patient required surgery for the complication. Two (5.9%) patients developed recurrent obstruction during a mean follow-up of 52 months. In one patient the obstruction was caused by adhesions and in another it was the result of an intra-abdominal abscess. Of 23 patients treated for ASBO at the time of Thow tube placement no patient (0%) developed recurrent ASBO during the follow-up period (total 110.5 patient-years). This study along with a review of the literature suggests that LITs decrease the risk of recurrent ASBO. The Thow tube, however, is easily placed and is associated with fewer and less severe complications than other LITs.

Granulosa cell tumor in a guinea pig.

Abdominal distention is a common clinical sign in guinea pigs and may have many causes. Abdominal ultrasonography may be a useful diagnostic tool in differentiation of abdominal disorders in guinea pigs. Ovariohysterectomy is indicated for granulosa cell tumors and cystic rete ovarii in guinea pigs.

Stereotactic core-needle breast biopsy by surgeons: minimum 2-year follow-up of benign lesions.

OBJECTIVE: To evaluate the reliability of stereotactic core-needle breast biopsy (SCNB) performed by surgeons to detect histologically benign tissue. SUMMARY BACKGROUND DATA: Stereotactic core-needle breast biopsy is widely used to obtain tissue for definitive pathologic diagnosis of mammographically suspicious breast lesions. It has an incidence of malignancy detection similar to that of open biopsy. The potential for sampling error is a concern. Minimal data regarding follow-up and failure rate are available, especially from series performed exclusively by surgeons. METHODS: Pertinent medical records of all patients who underwent SCNB between April 1995 and October 1997 were reviewed. Breast lesions were classified by mammographic Breast Imaging-Reporting and Data Systems (BI-RADS) categories before SCNB. Benign biopsy specimens were classified as nonproliferative or proliferative. Malignant lesions and those with atypical histopathology by SCNB were excluded from this analysis. All lesions initially reported as benign were followed up mammographically for at least 2 years for any suspicious change requiring repeat biopsy. RESULTS: During the 31-month period, SCNB was performed on 694 lesions in 619 patients. Histologic evidence of malignancy was found in 112 lesions (16%). The initial histologic diagnosis for the remaining 582 lesions was benign. Four hundred lesions were available for follow-up; of these, 373 (93%) were mammographically categorized as BI-RADS 3 (probably benign) or 4 (suspicious). Three hundred forty-three lesions were categorized as nonproliferative and 151 as proliferative (94 had combined nonproliferative and proliferative histology). Follow-up ranged from 24 to 48 months (mean 33 months). During the follow-up period, 87 lesions (21.8%) underwent either image-guided or open biopsy. At the time of follow-up rebiopsy, ductal carcinoma in situ was found in four lesions and infiltrating ductal carcinoma was found in one, for an overall false-negative rate of 4.3% (5/117) and a negative predictive value of 98.8% (395/400). For the five false-negative cases, the interval from initial SCNB to definitive diagnosis ranged from 7 to 36 months. No correlation was found between the type of initial histopathology and development of malignancy. CONCLUSIONS: These results support SCNB as an alternative to open biopsy and show the reliability of SCNB when benign pathology is obtained. However, given the possibility of sampling error and the nature of breast disease, close mammographic and clinical follow-up is necessary. The false-negative rate and negative predictive value in this series compare favorably with those in other reports, supporting the fact that surgeons can confidently use SCNB in the evaluation and treatment of breast disease.

Dermatologic changes associated with roquinimex immunotherapy after autologous bone marrow transplant.

BACKGROUND: Roquinimex (Linomide) is an immunotherapeutic agent used in conjunction with autologous bone marrow transplantation (ABMT) for treatment of acute and chronic myelogenous leukemia (AML and CML). This agent may induce graft-versus-host reactions (GVHR) as well as graft-versus-leukemia (GVL) effects. OBJECTIVE: We documented the incidence of acute cutaneous GVHR associated with roquinimex immunotherapy. The presence or absence of autologous GVHR was also correlated with a potential GVL effect in patients with CML treated with ABMT and subsequent roquinimex immunotherapy in the period after the transplant. METHODS: Fifteen patients undergoing bone marrow transplantation and roquinimex immunotherapy for CML were followed up, and clinicopathologic data were analyzed. RESULTS: Acute cutaneous GVHRs were observed in 6 of 15 patients (40%) treated with roquinimex. Ten of 11 evaluable patients receiving roquinimex exhibited eccrine sweat gland necrosis (ESGN) (90.9%), which was independent of the acute GVHR. Neither bone marrow engraftment status nor the survival rates of patients with and without GVHR was significantly different. CONCLUSION: Roquinimex immunotherapy enhances the incidence of GVHR and was associated with a high rate of ESGN in patients with CML who were undergoing ABMT. There was no significant association between ESGN and acute GVHR. Acute autologous GVHR caused by roquinimex did not correlate with a GVL effect in our study of 15 patients with CML.

Allergens and irritants transcriptionally upregulate CD80 gene expression in human keratinocytes.

The human CD80 costimulatory molecule is an important signal between professional antigen-presenting cells and T helper cells. The immunobiology of CD80 expression by keratinocytes, especially during allergic and irritant contact dermatitis, however, is less well understood. CD80 cell surface expression and gene transcription by keratinocytes was increased when keratinocytes were exposed to certain allergens (chemicals that induce inflammation via hapten-specific T cells) and irritants (chemicals that are toxic to epidermal cells). Therefore, the human CD80 promoter was cloned and luciferase reporter constructs containing various promoter fragments were engineered. Promoter mapping of these CD80 constructs in transiently transfected keratinocytes showed that a construct containing the proximal 231 bp immediately upstream of the transcription start site of the CD80 promoter was most active in keratinocytes and was inducible to a level ranging from 2- to 10-fold higher in keratinocytes treated with certain allergens and irritants, compared with untreated keratinocytes. This pattern of promoter fragment activity in keratinocytes is identical to that found in professional antigen-presenting cells. This is the first demonstration that the CD80 promoter is active in keratinocytes and that this activity is further increased in keratinocytes treated with certain allergens and irritants. These data suggest that allergens and irritants may, in part, break peripheral tolerance by their direct effects on keratinocyte costimulatory molecule expression, thereby facilitating interactions with epidermotropic T helper cells via the CD80-CD28 or CTLA-4 pathways.

Vacuum pack technique of temporary abdominal closure: a 7-year experience with 112 patients.

BACKGROUND: Temporary abdominal wound closure after celiotomy for trauma is often desirable. The ideal method of temporary closure should allow rapid closure, easy maintenance, and allow reexploration and wound repair with minimal tissue damage. Over the past 7 years, we have successfully used a vacuum closure system (the vacuum pack) for temporary management of the open abdomen. METHODS: Medical records of trauma patients undergoing exploratory celiotomy from April of 1992 to February of 1999 were reviewed. Demographic data as well as indications for open-abdominal management and complications of open-abdominal management were collected. RESULTS: Two hundred sixteen vacuum packs were performed in 112 trauma patients. Of the 216 vacuum packs placed, 2.8% were placed for increased intra-abdominal pressure, 5.3% for inability to achieve tension-free fascial closure, 20% for damage control, 55% for reexploration, and 16.7% for a combination of factors. Sixty-two patients (55.4%) went on to primary closure and 25 patients (22.3%) underwent polyglactin mesh repair of the defect followed by wound granulation and eventual skin grafting. Twenty-two patients (19.6%) died before abdominal closure was attempted. Five patients (4.5%) developed enterocutaneous fistulae. Five patients (4.5%) developed intra-abdominal abscesses. There were no eviscerations. Three patients (2.7%) required further explorations after abdominal closure. Overall mortality rate was 25.9%, none related to the vacuum pack. CONCLUSIONS: The vacuum pack is the temporary abdominal wound closure of choice in patients undergoing open abdominal management at our institution. Primary closure is achieved in the majority of patients with a low rate of complication. The technique is simple and easily mastered. Technical complications are rare and easily repaired.

The evaluation of subatmospheric pressure and hyperbaric oxygen in ischemic full-thickness wound healing.

We evaluated the efficacy of subatmospheric pressure and hyperbaric oxygen (HBO) as adjuncts in the treatment of hypoxic full-thickness wounds in a rabbit model. We hypothesized that subatmospheric pressure and HBO independently are effective in improving wound healing in the ischemic wound model and that when they are used in combination there is an increased positive effect on wound healing. Using a standard ischemic wound model four full-thickness wounds were created on each ear of 41 male New Zealand white rabbits (N = 82 ears). On each rabbit one ear was dressed with the vacuum-assisted closure (VAC) device and connected to suction; the other was dressed identically without the suction and suction tubing. Twenty rabbits were treated with HBO daily for 10 days at 2.0 atmospheres absolute for 90 minutes plus descent and ascent times. Necropsy on all rabbits was performed on postoperative day 10. Four ischemic wound treatment groups were evaluated: Group 1 (N = 21) VAC dressing alone; Group 2 (N = 20) VAC dressing plus HBO; Group 3 (N = 21) VAC dressing to suction alone; and Group 4 (N = 20) VAC dressing to suction and HBO. Using light microscopy a veterinary pathologist blinded to treatment groups quantified peak granulation tissue, granulation tissue gap, and epithelialization tissue gap. Data were analyzed by analysis of variance with significance indicated by P < 0.05. Statistical significance was found in a comparison of VAC dressing to suction and VAC dressing alone for peak granulation tissue and granulation tissue gap both with and without use of HBO. VAC device use appears to increase the rate of healing in a rabbit ischemic wound model. HBO therapy did not significantly affect the rate of healing in this model.

Clinical research during surgery residency: the Chattanooga approach.

PURPOSE: The nontraditional clinical research rotation at the University of Tennessee College of Medicine-Chattanooga Unit is described and its efficacy evaluated by the number of peer-reviewed publications produced. METHODS: In 1988, a mandatory year of clinical research was added to the general surgery curriculum. The year is completed in 3 4-month rotations, 1 each during the PGY-2, PGY-3, and PGY-4 years. Curriculum vitae of 31 graduates of the traditional 5-year residency were evaluated for publications produced during residency and 1 year beyond training. Comparison was made to 15 subjects; 8 were 6-year graduates and 7 were PGY-4, PGY-5, or PGY-6 residents having completed the research year. Statistical analysis used the Mann-Whitney U test for nonparametric data as well as an independent t test with significance set at 0.05. Publications were verified by a MEDLINE search. Six-year graduates also completed a questionnaire regarding their research experience. RESULTS: Graduates of the 5-year program completed an average of 0.94 publications during residency, whereas 6-year graduates completed an average of 2.67 publications (p < 0.001). Opinions varied regarding desire to pursue research and the benefit of the research year. CONCLUSIONS: Our results demonstrate that basic science research is not the only model; academic productivity can be improved with an additional year devoted to clinical research. Advantages to this nontraditional approach include decreased likelihood of decline of clinical skills and knowledge, ability to maintain long-term projects, and a physical and mental break from a demanding clinical residency.

The imidazoquinolines, imiquimod and R-848, induce functional, but not phenotypic, maturation of human epidermal Langerhans' cells.

Imiquimod (R-837) and its more potent derivative (R-848) are imidazoquinolines that have adjuvant activity in cultured human mononuclear cells. Its mechanism of action on epidermal antigen-presenting cells is not known. The purpose of the present investigation was to determine whether imiquimod and R-848 affect human epidermal Langerhans' cells' (LC) in vitro maturation. Pulse incubations (6-16 h) of cultured unfractionated epidermal cells or highly enriched LC suspensions with either imiquimod or R-848 (0. 05-5.0 microg/ml of culture medium) reproducibly enhanced their ability to induce T-cell proliferation in a primary mixed lymphocyte reaction. There was a 30 to 300% increase in T-lymphocyte proliferation induced by either imiquimod- or R-848-treated LC when compared to control, untreated LC. IFN-gamma secretion by T-lymphocytes stimulated by imiquimod- or R-848-treated LC was increased compared to control, untreated LC. After a 6-h incubation, phenotypic analysis of control-, imiquimod-, or R-848-treated LC indicated that such antigen-presenting cells were in an "intermediate" state of maturation (CD1a(+), HLA-DR, DP, DQ(bright+), CD40(low+), CD86(high+), and CD80(low+)). RNase protection assays demonstrated that either imiquimod or R-848 treatments increased steady-state transcripts encoding for IL-12 p40, IL-1beta, TNF-alpha, and IL-1 receptor antagonist by LC. These data indicate that imiquimod and R-848 dissociate the functional maturation (cytokine-mediated) and phenotypic maturation of epidermal LC. These data warrant further exploration for the use of imidazoquinoline-treated LC or other DC subsets for processing and presentation of viral peptides to Th-lymphocytes as a novel vaccine strategy to induce protective antiviral responses.

Traumatic fracture of the hyoid bone: three case presentations of cardiorespiratory compromise secondary to missed diagnosis.

Hyoid bone fractures secondary to blunt trauma other than strangulation are rare (ML Bagnoli et al., J Oral Maxillofac Surg 1988; 46: 326-8), accounting for only 0.002 per cent of all fractures. The world literature reports only 21 cases. Surgical intervention involves airway management, treatment of associated pharyngeal perforations, and management of painful symptomatology. The importance of hyoid fracture, however, rests not with the rarity of it, but with the lethal potential of missed diagnosis. We submit three cases with varying presentations and management strategies. All three of our cases incurred injury by blunt trauma to the anterior neck. Two patients required emergent surgical airway after unsuccessful attempts at endotracheal intubation. One patient presented without respiratory distress and was managed conservatively. After fracture, the occult compressive forces of hematoma formation and soft tissue swelling may compromise airway patency. It is our clinical observation that hypoxia develops rapidly and without warning, leading to cardiorespiratory collapse. With endotracheal intubation prohibited by obstruction, a surgical airway must be established and maintained. Recognition of subtle clinical and physical findings are critical to the diagnosis of laryngotracheal complex injuries and may be life-saving in many instances. To ensure a positive outcome, a strong degree of suspicion based on mechanism of injury is mandated.

Posttraumatic carotid cavernous fistula: frequency analysis of signs, symptoms, and disability outcomes after angiographic embolization.

OBJECTIVE: To increase awareness and understanding of posttraumatic carotid cavernous fistula (PTCCF) with the intent to expedite diagnosis and treatment of this disabling injury, a 14-year retrospective review of patients with angiographically identified PTCCF was conducted at this Level I trauma center. A frequency analysis of signs, symptoms, and disability was performed. The impact on disability of demographics, number of embolization attempts required for closure of the PTCCF, and time from injury to diagnosis was assessed by t test for independent samples. RESULTS: Nine patients were diagnosed with 10 PTCCFs. Mean patient age was 41.5 years. All patients with PTCCF had basilar skull fracture, loss of consciousness, bruit, and chemosis; 90% had exophthalmos; 70% had visual changes; 50% complained of headache; and 80% had some lasting disability. Mean age of patients with partial to total disability was 47 years, while the mean age of patients without lasting disability was 19.5 years (p = 0.013). No statistical correlation could be found between disability and sex, blunt versus penetrating injury, days to diagnosis, or number of embolization attempts. CONCLUSION: Patients sustaining head trauma with basilar skull fractures and presenting with the described signs and symptoms should be evaluated for PTCCF. Risk of disability does not appear to be influenced by number of attempts at embolization or time to diagnosis. However, age may have a significant impact on outcome.

B7-1 overexpression by thymic epithelial cells results in transient and long-lasting effects on thymocytes and peripheral T helper cells but does not result in immunodeficiency.

The B7-1 (CD80) molecule provides costimulatory function for the activation of T helper lymphocytes upon encounter with antigen. To investigate the role of this molecule in thymocyte maturation, we have generated transgenic (Tg) mice in which CD80 expression is driven by the keratin 14 promoter (K14). This overexpression of CD80 resulted in the loss of detectable cell surface CD28 expression on thymocytes and a significant reduction in both the surface T cell receptor expression and the ratio of CD4(+) to CD8(+) single-positive thymocytes in Tg animals compared to nontransgenic (non-Tg) controls. While many of these defects were transient, the significant decrease in CD4(+) versus CD8(+) T cell ratio persisted peripherally. Peripheral T cells from these Tg mice were found to be significantly hyporesponsive to T cell mitogens and in mixed leukocyte reaction, effects that our data indicate are due to reduced IL-2 production by Tg T cells upon activation. Despite these functional defects, immunization with both complex and simple protein antigens produced no differences in the proliferative or humoral responses to these antigens between Tg and non-Tg groups. These data indicate that thymic CD80 signaling results in the deletion of significant numbers of CD4(+) T cells but does not culminate in antigen-specific immunodeficiency.

Mediastinal evaluation utilizing the reverse Trendelenburg radiograph.

When thoracic aortic rupture is suspected, a 45-degree reverse Trendelenburg (RT) anteroposterior (AP) chest radiograph should place the mediastinal structures in a more appropriate position and allow a more accurate evaluation than a supine AP radiograph. One hundred ninety-one consecutive hemodynamically stable adult patients with major blunt thoracic trauma were initially evaluated for mediastinal abnormalities associated with aortic disruption by both supine AP chest radiograph and an AP chest radiograph with the patient in 45-degree RT position. One hundred four patients underwent contrast aortography based on mediastinal abnormalities detected on the supine AP chest radiograph. Twenty of these patients had abnormal aortograms demonstrating traumatic aortic disruption confirmed at surgery. Supine and RT chest radiographs were retrospectively compared in a blinded fashion to evaluate their specificity and positive predictive value for detection of traumatic thoracic aortic rupture. If RT chest radiographic findings had been used to determine the need for further assessment, 29 angiograms (26%) would have been eliminated, specificity would have increased from 52 per cent to 69 per cent, and positive predictive value would have increased from 19 per cent to 27 per cent. Both supine and RT chest radiographs demonstrated mediastinal widening in all 20 patients with abnormal aortograms, with no missed thoracic aortic disruptions (100% sensitivity). This study indicated that the RT chest radiograph may be used instead of the standard supine radiograph as the initial screen for mediastinal evaluation, maintaining a high sensitivity and eliminating the cost and morbidity of many unnecessary aortograms.

Sledding injuries in the southeastern United States.

BACKGROUND: Heavy ice and snow accumulation combined with record low temperatures in Chattanooga, Tennessee, from February 2-6, 1996, contributed to many sledding injuries. METHODS: We retrospectively reviewed medical records of emergency visits to seven area hospitals from February 2-6, 1996. We further reviewed sledding injury records. Sledding was defined as sliding on snow or ice using any device except skis. RESULTS: Of 2,134 emergency room visits, 241 patients had 310 sledding injuries. Ages of patients ranged from 3 to 53 years (mean, 18.9; median, 16). One hundred twenty-eight injuries were severe. These included extremity injuries (65), head injuries (28), chest injuries (10), intra-abdominal injuries (10), vertebral column fractures (11), and pelvic fractures (4). Thirty-six patients required inpatient hospitalization; 18 had surgery. The minimum healthcare costs associated with these injuries were estimated at $220,000. CONCLUSIONS: Major trauma potential is associated with sledding, especially where significant winter storms are uncommon. Level I trauma centers should seasonally incorporate sledding safety into community-wide injury prevention programs.

Primary aortojejunal fistula: a case report.

Primary aortoenteric fistulae (AEFs) are extremely rare vascular entities, with fewer than 250 cases reported in the world medical literature as of 1996. Incidence is less than 1 per cent, with a mortality ranging from 33 to 85 per cent. Atherosclerosis remains the most common etiology, accounting for more than two-thirds of the cases reported. Other etiologies include carcinoma, ulcers, gallstones, diverticulitis, appendicitis, and foreign bodies. Early diagnosis is crucial for survival and mandates recognition of the typical "herald bleed." Additional findings on initial presentation frequently include flank pain, abdominal pain, hematemesis, melena, and an abdominal mass. More than 80 per cent of primary AEFs involve the duodenum, with the overwhelming majority located in the third or fourth portion. Successful management of primary AEF requires a high index of suspicion for diagnosis and prompt surgical intervention for survival.

Initial cervical exploration for parathyroidectomy is not benefited by preoperative localization studies.

Published data is controversial as to the ability of preoperative localization studies (PLS) to enhance the outcome of initial cervical exploration in patients with primary hyperparathyroidism (PHPT). One surgeon's experience was reviewed to compare surgical success, operative time, and morbidity of initial cervical exploration for PHPT in patients who had undergone PLS versus those who had not. From August 1991 to September 1997, 95 patients who had not undergone prior central cervical exploration presented for surgical management of PHPT. Sixty-seven patients underwent initial cervical exploration without any PLS having been performed (Group A). Twenty-eight patients underwent PLS, either alone or in combination, before surgical intervention (Group B). Analysis of intergroup variability was conducted upon the data available using a two-tailed t test for independent samples. In addition, the sensitivities and positive predictive values of the PLS were calculated using study reports and operative and histologic findings. There was no statistically significant difference in surgical success between those patients who had PLS and those that did not undergo PLS. Sixty-four of 67 patients (95.5%) not having PLS were cured with initial surgery, while 27 of 28 patients (96.4%) who had PLS were surgically cured. Mean postoperative calcium and intact parathormone levels were similar between the two groups, and the mean operative time did not differ. Permanent hypocalcemia occurred in one patient, and five patients had transient hoarseness. Thirty-six total PLS were obtained at an average cost of $752.68/patient, and seven patients underwent multiple tests. Overall, sestamibi scan had the highest positive predictive value (81%). For adenomatous disease alone, sestamibi scan was the most sensitive (83%). Our study shows that for matched groups limited to age, sex, and clinical diagnosis, the use of PLS did not shorten operative time, decrease complication frequency, nor alter the success of the operation as measured by postoperative calcium and parathormone levels. Therefore, routine use of preoperative localization studies before initial cervical exploration for PHPT cannot be recommended.

Combination endovascular and open treatment of peripheral arterial occlusive disease performed by surgeons.

The endovascular treatment of peripheral arterial occlusive disease has historically been performed by interventional radiologists and cardiologists. With additional training in endovascular techniques, surgeons become uniquely suited to manage arterial lesions with both endovascular and conventional surgical techniques. Over a 14-month period, 13 patients underwent combination endovascular and open reconstruction on limbs with peripheral arterial occlusive disease. There were 10 males and 3 females. The mean age was 66 years. All procedures were performed in the operating room by surgery residents under the direct supervision of vascular surgeons. After intraoperative angiography, 26 arterial lesions underwent percutaneous transluminal angioplasty (aorta, 1; common iliac, 14; external iliac, 10; superficial femoral, 1). Twenty-five of 26 lesions were further treated with intraluminal stent placement, the lone exception being a case of superficial femoral artery angioplasty. Concomitant open reconstruction was performed on all limbs, 14 as outflow and 1 as inflow. There were two cases of procedural morbidity and one perioperative death secondary to myocardial infarction. There were no wound-related complications. The mean ankle-brachial index of the affected lower extremity improved from 0.41 (+/- 0.15) to 0.74 (+/- 0.14) at 30 days. Mean follow-up was 8 months (range, 2-14). Based on our early experience, simultaneous combination endovascular and open reconstruction of multisegment arterial occlusive disease can be performed safely and efficiently by surgeons.

Characterization of the altered cutaneous reactivity of transgenic mice whose keratinocytes overexpress B7-1.

B7-1 (CD80) is a second signal molecule usually associated with "professional" APCs that prevents the induction of T-cell clonal anergy and induces IL-2 production during antigen presentation. Tg mice whose epidermal KC overexpress B7-1 exhibit exaggerated and persistent CHS to a variety of haptens that lasts up to 8 weeks after hapten challenge. These Tg mice also exhibit significantly enhanced ear-swelling responses to irritants that are not persistent. Exaggerated CHS was not reflected in the draining lymph node. T-lymphocyte proliferative responses after sensitization and local challenge with haptens, as there were no significant differences between the B7-1 Tg and the NTg mice. However, RT-PCR analysis of mouse ear skin at the hapten challenge site indicated that B7-1 Tg mice had an alteration in the kinetics of in situ lymphokine transcripts compared to NTg mice: IFN-gamma transcripts were first detectable in Tg mouse skin at 2 weeks versus 24 h for NTg mice. RNase protection assays to detect inflammatory cytokine transcripts at hapten application sites indicated that B7-1 Tg mice responded to hapten application with increased TNF-alpha, IL-6, and TNF-beta transcripts compared to NTg mice. Thus, hapten-induced ear swelling in these Tg mice may be mediated by enhanced inflammatory cytokines during the early phase (1-14 days). IFN-gamma-producing lymphocytes may be responsible for the late phase of the ear-swelling response (14-42 days). These data indicate that B7-1 overexpression by KC in mouse skin directly or indirectly affects the nature of cutaneous inflammation induced by haptens and irritants.

Molecular analysis of skewed Tcra-V gene use in T-cell receptor beta-chain transgenic mice.

The influence of beta-chain diversity on the expressed T-cell receptor (TCR) alpha-chain repertoire was investigated using transgenic mice which exclusively express a single rearranged TCR beta-chain gene. Analysis of these mice using alpha-chain-specific recombinant cDNA libraries showed that expression of the transgene-encoded beta chain results in significant skewing in Tcra-V gene segment usage vs nontransgenic mice. Skewing was most pronounced towards alpha chains using TCRA-V segments. Sequence analysis of Tcra-V8-containing genes from transgenic T cells revealed predominant use of a single Tcra-J segment (Tcra-J24), which was not detected in Tcra-V8 containing genes isolated from nontransgenic T cells. Further analysis revealed that co-expression of Tcra-V8 with Tcra-J24 in beta-transgenic mice is exhibited almost exclusively by CD4+ T cells, and is associated with a limited number of closely related N-regions. Analysis of transgenic CD8+ T cells demonstrated predominant co-expression of Tcra-V8 with another Tcra-J (Tcra-J30), together with a different, limited N-region sequence. We conclude that the composition of expressed beta chains can profoundly influence the selection of companion alpha chains expressed in the periphery, and that alpha-chain N and J regions play a crucial role in discriminating between class I vs class II major histocompatibility complex (MHC)-restricted recognition. Further, these results are in agreement with recent data concerning the crystal structure of the TCR, and most consistent with a model for TCR structure in which the complementarity determining region (CDR)3alpha domain participates in direct contact with the MHC.