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This study describes the first reported case of a combined heart-lung-kidney transplantation. Our patient suffered from hypertrophic cardiomyopathy due to long-standing hypertension with Dana Point Classification Group 2 pulmonary hypertension from the underlying cardiac disease, along with renal failure necessitating renal replacement therapy. Twenty months after the transplant procedure, she has stable pulmonary and renal function, plus has resumed a normal daily life with improving exercise tolerance. We propose that a combined heart-lung-kidney transplantation may be an acceptable therapeutic option for carefully selected patients with advanced, concomitant cardiac, pulmonary, and kidney disease., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The immunosuppressive drug cyclosporin A (CsA) represents the standard preventive treatment of graft-versus-host disease (GVHD), the main complication of allogeneic hematopoietic stem cell transplantation (HSCT). However, its efficacy is only partial and many patients develop lethal GVHD despite CsA. A strategy of genetic immunosuppression based on conditional elimination of donor T cells expressing the Herpes simplex type 1 thymidine kinase (TK) suicide gene was recently developed. In this system, ganciclovir (GCV) selectively kills dividing but not quiescent TK T cells. Since CsA is known to have a cytostatic effect on T cells, it could negatively interfere with the division-dependent TK gene therapy. We thus tested whether administration of CsA would antagonize elimination of alloreactive donor TK T cells mediated by GCV in a murine model of GVHD. In vivo experiments revealed that, contrary to GCV, CsA only transiently controlled alloactivation-induced T cell proliferation, and likewise could not prevent lethal GVHD. When T cells resumed proliferation under CsA, they were however still sensitive to GCV. Survival, as well as immune reconstitution, was excellent in mice treated with GCV alone or in combination with CsA. These observations should help to design improved suicide gene therapy trials in the field of allogeneic HSCT.

We present a 64-year-old patient with a 9-cm firm, irregular penile mass associated with phimosis, erectile dysfunction, and voiding difficulty. After he reluctantly admitted to multiple penile mineral oil self-injections for enlargement, surgical excision was performed. Pathologic examination was consistent with mineral oil granuloma (paraffinoma). Within several weeks after surgery, his erectile dysfunction and voiding complaints resolved. Paraffinomas have been encountered with the use of various oily substances injected for cosmetic purposes. Despite early warnings, these agents continued to be used to treat conditions ranging from hemorrhoids to wrinkles and even baldness. Fortunately, most of these fads have been abandoned by medical professionals, but the complicating lesions have been documented as having lag times as long as 30 years. Complete surgical excision remains the treatment of choice to prevent recurrence. Increased public awareness is needed for the prevention of this physically and psychologically debilitating problem.

After non-T-cell-depleted allogeneic hematopoietic stem cell transplantation (HSCT), both alloreactive and homeostatic signals drive proliferation of donor T cells. Host-reactive donor T cells, which proliferate on alloantigen stimulation, are responsible for the life-threatening graft-versus-host disease. Non-host-reactive donor T cells, which proliferate in response to homeostatic signals, contribute to the beneficial peripheral T-cell reconstitution. The elimination of alloreactive T cells is a major therapeutic challenge for HSCT and would greatly benefit from their specific identification. After T-cell transfer in lymphopenic recipients, the present results show that alloreactive T cells rapidly divided; up-regulated CD69, CD25, and CD4 molecules; and down-regulated CD62L. In contrast, nonalloreactive T cells started to divide later and did not up-regulate CD69, CD25, and CD4. Thus, these 2 cell populations can be effectively discriminated. This should facilitate the specific depletion of alloreactive T cells in allogeneic HSCT.

After allogeneic hematopoietic stem cell transplantation (HSCT), mature transplanted T cells play a major role in restoration of the immune system. However, they can also induce a life-threatening complication: graft-versus-host disease (GVHD). Suicide gene therapy of GVHD aims to selectively eliminate alloreactive T cells mediating GVHD while sparing nonalloreactive T cells that should contribute to immune reconstitution. It was demonstrated previously that treatment with ganciclovir (GCV) can control GVHD in mice by killing donor T cells engineered to express the thymidine kinase (TK) suicide gene. TK allows phosphorylation of nontoxic GCV into triphosphate GCV, which is selectively toxic for dividing cells. Thus, in the TK-GCV system, the specificity of cell killing depends on the cycling status of TK T cells rather than allogeneic recognition. This is a potential drawback because in recipients of lymphopenic allogeneic HSCT, alloreactive and homeostatic signals drive the proliferation of donor T cells. It is shown here that the onset of alloreactive T-cell division occurs earlier than that of nonalloreactive T cells, thus establishing a time frame for GCV administration. A 7-day GCV treatment initiated at the time of HSCT allowed efficient prevention of GVHD, while sparing a pool of nondividing donor TK T cells. These cells later expanded and contributed to the replenishment of the recipient immune system with a diversified T-cell receptor repertoire. These results provide a rationale for designing the therapeutic scheme when using TK-GCV suicide gene therapy in allogeneic HSCT.

The main complications following allogeneic hematopoietic stem cell transplantation are graft-versus-host disease and poor immune reconstitution leading to severe infections. Mature donor T cells present in the transplant facilitate T cell reconstitution in adults, but also induce graft-versus-host disease, which itself impairs immune reconstitution. Thus, infusing a large number of donor T cells with a diverse repertoire should accelerate functional immune reconstitution after transplantation, only if graft-versus-host disease can be controlled. We previously demonstrated that preventive treatment with ganciclovir could control graft-versus-host disease in mice if donor T cells are made to express viral thymidine kinase as a "suicide" gene. Here we evaluated the recovery of functional antiviral immune responses in such mice. Irradiated mice received an allogeneic hematopoietic stem cell transplantation with thymidine kinase-expressing T cells and were protected from graft-versus-host disease by ganciclovir treatment, and then challenged with lymphocytic choriomeningitis virus. Grafted mice could mount efficient antilymphocytic choriomeningitis virus immune responses leading to viral elimination. Furthermore, when transplanted cells were obtained from mice previously immunized against lymphocytic choriomeningitis virus, grafted mice developed memory-type accelerated responses against the virus. We conclude that efficient graft-versus-infection effects can be mediated by naive T cells and memory donor T cells that persist after suicide gene therapy for prevention of graft-versus-host disease.

Standard immunosuppressive drugs used for allogeneic organ transplantation do not specifically target alloreactive T cells and must be given for the lifetime of the patient, resulting in significant morbidity and mortality. We aimed to induce experimental immune tolerance to vascularized heart allograft using a suicide gene allowing selective elimination of dividing T cells expressing Herpes simplex virus type 1 thymidine kinase upon ganciclovir administration. We show that without ganciclovir, transgenic mice selectively expressing thymidine kinase in T cells rejected a vascularized cardiac allograft in 7 days. In contrast, allograft was definitively accepted after a 7-day course of ganciclovir initiated at the time of allotransplantation. Interestingly, T cells from both rejecting and tolerant mice proliferated in response to donor or third-party allogeneic stimulation. This state of tolerance was challenged through a second vascularized cardiac allotransplantation. Third-party allografts were rejected while those syngeneic to the first allograft were accepted without any additional treatment. These results show that short-term pharmacogenetic immunosuppression can induce long-lasting, robust, and specific tolerance to solid vascularized allograft without generalized continuous immunosuppression.

Background: Control of antidonor activated T cells involved in allograft rejection while preserving immunocompetence is a challenging goal in transplantation. Engineered T cells expressing a viral thymidine kinase (TK) suicide gene metabolize the nontoxic prodrug ganciclovir (GCV) into a metabolite toxic only to dividing cells. We evaluated this suicide gene strategy for inducing transplantation tolerance in mice., Methods: Transgenic mice expressing TK in mature T cells were analyzed for (i) specific T-cell depletion under GCV treatment upon various stimulations; (ii) outcome of allogeneic nonvascularized skin or heart allografts under a short 14-day GCV treatment initiated at the time of transplantation; and (iii) the capacities of T cells from such allotransplanted mice to proliferate in mixed lymphocyte reactions and to induce graft-versus-host disease in irradiated recipients with the genetic background of the donor allograft., Results: Upon in vitro or in vivo GCV treatment, only activated dividing TK T cells but not B cells were efficiently depleted. Acute rejection of allogeneic grafts was prevented and a significant prolongation of graft survival was obtained, although associated with signs of chronic rejection. Prolonged skin graft survival correlated with decreased in vitro and in vivo T-cell reactivities against donor alloantigens, whereas overall immunocompetence was preserved., Conclusions: Efficient and specific depletion of alloreactive TK T cells can be achieved by administrating GCV. These results open new perspectives for the control of allogeneic graft rejection using suicide gene therapy.

The treatment of porphyria cutanea tarda (PCT) in patients with chronic renal failure poses a therapeutic challenge. In the absence of renal failure, phlebotomy and oral antimalarials have been the standard of care for PCT. However, in the presence of renal failure, associated chronic anemia often precludes the use of phlebotomy, and oral antimalarials are usually ineffective. We describe a patient with severe symptomatic PCT and chronic renal failure whose disease was successfully managed with a combination of high-dose erythropoietin and small volume phlebotomy. We also review several previously reported approaches to management of PCT in the setting of renal failure, which include small repeated phlebotomy, erythropoietin, deferoxamine, chloroquine, plasma exchange, high-efficiency/high-flux hemodialysis, cholestyramine, charcoal hemoperfusion, and kidney transplantation. An algorithm for the management of these patients is proposed.

Background: In current practice, contrast echocardiography is performed with single or multiple bolus injections, which often result in an uncontrolled period of attenuation followed by transient left ventricular opacification (LVO). Because a "slow bolus" appears to reduce attenuation and prolong LVO, we hypothesized that a controlled infusion of contrast might provide a more uniform contrast effect with less attenuation and longer contrast duration., Methods and Results: We sought to test the hypothesis by using an infusion of contrast (DEFINITY [perflutren], The DuPont Pharmaceuticals Co, Medical Imaging, North Billerica, Mass) that is stable when diluted in saline in a randomized, multicenter, controlled, crossover trial. Sixty-four patients with poor noncontrast images were recruited at 3 centers and randomly assigned to 2 single "slow" bolus injections of contrast (10 microL/kg each over a period of 30 to 60 seconds) or an infusion (1. 3 mL in 50 mL normal saline initially at 4.0 mL/min) of contrast. Patients then returned within 24 to 72 hours for the alternative form of contrast delivery. Three independent experienced echocardiographers viewed 30 seconds of videotape for all optimal baseline and optimal contrast images to score LVO and qualitatively assessed endocardial border evaluability. The duration of adequate LVO then was independently assessed by review of the entire videotape. Three independent sonographers traced single-frame, digitally captured images to measure the length of the contiguous endocardial border visualized. Both bolus and infusion administration demonstrated improved LVO (>90% by all blinded readers, P <.01) and endocardial border visualized (mean increase of 1.8 to 4.7 cm at both end-diastole and end-systole, all P <.05) as compared with baseline images. However, contrast infusion resulted in a longer duration of LVO (range of mean durations for each reader, 158 to 174 seconds longer, P <.05) and a shorter duration of attenuation (18 to 54 seconds, P <.05) compared with either bolus injection. There were no severe adverse events with contrast infusion., Conclusions: Contrast echocardiography delivered as an infusion optimizes the contrast effect by decreasing the attenuation period, extending the LVO duration, and providing a uniform contrast effect that may be useful in obtaining multiple echocardiographic views, stress echocardiography, myocardial perfusion imaging, and applications in which blood flow must be quantified.

Background: The use of donor T cells expressing the herpes simplex thymidine kinase (HSV-TK) gene followed by ganciclovir (GCV) treatment could allow for specific modulation of the alloreactivity occurring after bone marrow transplantation. We are presently exploring such an approach in a phase I clinical trial., Methods: To examine the beneficial effect of administrating HSV-TK-expressing donor T lymphocytes +/- GCV treatment on acute graft-versus-host disease (aGVHD) control, irradiated Balb/c or C57BL/6 mice underwent transplantation with allogeneic bone marrow cells in conjunction with CD3+ allogeneic splenocytes from transgenic mice expressing an HSV-TK transgene. GCV treatment was initiated upon the occurrence of severe aGVHD., Results: GCV treatment resulted in a 40-60% long-term survival rate of GVHD-free recipients having received HSV-TK-expressing T cells, whereas only 0-6% of mice survived without GCV treatment. Lethal aGVHD occurred in all the control animals having received non-HSV-TK-expressing T cells, irrespective of GCV treatment., Conclusion: Our results demonstrate that the administration of donor HSV-TK-expressing T cells to hematopoietic stem cell graft recipients followed by GCV treatment at the onset of severe aGVHD significantly reduces aGVHD-induced mortality and results in GVHD-free surviving recipients.

Deficiencies of 7 enzymes in the heme biosynthetic pathway result in the development of porphyrias. Two of the porphyrias, aminolevulinate dehydratase deficiency porphyria and acute intermittent porphyria do not have cutaneous findings. Cutaneous findings in the other porphyrias could be subdivided into acute phototoxicity and subacute phototoxicity. In addition, 2 of the porphyrias, hereditary coproporphyria and variegate porphyria have both cutaneous and neurovisceral findings. Now that chromosomal assignments for all the genes of the defective enzymes have been mode, prenatal diagnosis is possible for congenital erythropoietic porphyria, and in vitro gene therapy has been successfully performed for congenital erythropoietic porphyria and erythropoietic protoporphyria.

Donor T cells are beneficial for engraftment, immune reconstitution, and antileukemic effects after allogeneic marrow transplantation, but they also cause graft-versus-host disease. Treatment with ganciclovir can control graft-versus-host disease if donor T cells are genetically engineered to express viral thymidine kinase. Clinical protocols with thymidine kinase-expressing T cells currently prescribe the curative use of ganciclovir for genetic immunosuppression only after clinical manifestations of graft-versus-host disease have appeared. The aim of this work was to compare early/preventive versus delayed/curative treatment of GVHD. Here, we found that ganciclovir administered early after experimental marrow transplantation was highly effective in preventing graft-versus-host disease caused by thymidine kinase-expressing T cells, and surviving recipient mice were able to mount a T cell-dependent B cell response. In contrast, curative ganciclovir administration later after transplantation was much less effective in treating graft-versus-host disease and surviving recipients had markedly impaired immune function. These findings should be considered in the development of future clinical trials using thymidine kinase-expressing T cells; to date, such trials have envisaged the use of GCV to treat only declared graft-versus-host disease. The use of thymidine kinase-expressing T cells for conditional elimination of activated T cells after allogeneic marrow transplantation offers a promising new approach for the control of graft-versus-host disease. The versatility of the thymidine kinase/ganciclovir system offers clinical options depending on whether thymidine kinase-expressing T cells are infused at the time of bone marrow transplantation or in a delayed manner, and depending on whether GCV is administered in an early/preventive or delayed/curative manner. The rationale underlying these options is more complex than it may appear and is likely to have a profound impact on the efficacy of such treatments. In the present work, we analyze the immunological impact when GCV is administered in an early/preventive or delayed/curative manner. Our results demonstrate that the delayed/curative strategy is clearly associated with severe immunological defects. To our knowledge, this is the first report of immunodeficiency subsequent to suicide gene therapy for GVHD.

Background: Echocardiographic contrast enhancement of the left ventricle has diagnostic value in the assessment of regional and global left ventricular (LV) function. The efficacy of both octafluoropropane-filled human albumin microbubbles (OCTA) and of air-filled human albumin microbubbles (AIR) for LV endocardial delineation and qualitative LV opacification has previously been reported. However, pulmonary disease, obesity, impaired LV function, and decreased echogenicity may diminish the efficacy of contrast agents for LV opacification. The purpose of this study was to compare the susceptibility of 2 contrast agents currently approved by the Food and Drug Administration to these biologic factors., Methods: To compare quantitative LV opacification with OCTA (0.2, 0. 5, 3.0, 5.0 mL) versus AIR (0.08 mL/kg, 0.22 mL/kg), we performed videodensitometry in 199 patients (average age 59.2 +/- 13.3 years, 79% men) studied in 2 identical, prospective, multicenter, blinded trials, of whom 74 had impaired LV function, pulmonary disease, or both, 70 were obese (body mass index >30 kg/m(2)), and 45 were nonechogenic (>/=4 of 6 endocardial segments were not seen in the apical 4-chamber view). Changes in videodensity from noncontrast to contrast agent with the same gain settings were determined at end diastole and end systole (gray scale 0 to 255 U) for 2 regions of interest: left ventricle apex-to-mid-cavity and mid-cavity-to-base. The relative influence of clinically evident pulmonary disease, impaired LV function on echocardiography, and echogenicity on LV opacification produced by both contrast agents was determined by multivariate analysis., Results: Significant videodensity increases ranging from 67% to 143% were observed with both agents. At the recommended initial doses (0.5 mL for OCTA, 0.22 mL/kg for AIR), OCTA produced greater opacification than AIR in both regions of interest and at both phases of the cardiac cycle. Poor LV function was associated with decreased LV opacification for AIR but not for OCTA. Diminished echogenicity was more strongly associated with impaired opacification for AIR than for OCTA. Obesity and clinically evident pulmonary disease were associated with diminished chamber opacification with both OCTA and AIR., Conclusions: In addition to the superiority of octafluoropropane-filled microspheres to air-filled microspheres for LV opacification, the efficacy of OCTA is relatively unaffected by impaired LV function and is less susceptible to the effects of poor echogenicity than AIR.

The development of suicide genes and progress in retroviral gene transfer to T-cells open new perspectives for the treatment of graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT) for leukemia and lymphoma. Indeed, suicide genes that metabolize inactive prodrugs into compounds toxic for dividing cells provide a powerful means for the pharmacogenetic control of T-cell reactivity. Here, we demonstrate the selective destruction of activated TK-transgenic T-cells in vivo and develop two new transgenic lines which should be useful for preclinical studies of suicide gene therapy strategies for GVHD.

In recent years, considerable interest has arisen in understanding the mechanisms of the CD4 gene transcriptional control which resulted in the identification of a promoter, enhancers and a silencer. While the murine CD4 gene promoter has been well studied, little is known about its human counterpart that we previously identified as a 1.1 kb region. Here, we show that the -170/+20 region represents a minimal tissue-specific promoter with a size compatible with its inclusion in viral vectors for gene therapy. In addition, mutational analyses provided evidence that this fragment contains three regions critical for transcriptional activity: an initiator-like sequence, an Ets consensus site and an ATF consensus site. The latter site is absent in the murine promoter, suggesting that some differences exist between the transcriptional control of the human and murine CD4 genes.

Dividing cells expressing the Herpes simplex type 1 thymidine kinase (TK) can be killed upon ganciclovir treatment. Likewise, conditional cell knock-out can be obtained in transgenic mice expressing a TK gene placed under the control of tissue-specific regulatory sequences. Such animals provide powerful experimental systems for assessing the functional role of specific cell populations through their time-controlled ablation. However, whatever the regulatory sequences used, a leaky toxic overexpression of TK in testis renders male TK-transgenic mice sterile and prevents the generation of homozygous TK-expressing animals. To solve this problem, we designed a truncated TK variant (delta TK) not expressed in the testis. We generated transgenic mice expressing delta TK under the control of lymphocyte-specific regulatory sequences derived from the CD4 gene. The delta TK protein expressed in T-lymphocytes allowed the conditional ablation of activated T-cells in vitro and in vivo. Importantly, for one transgenic line we could generate fertile homozygous mice harboring a functional delta TK transgene. delta TK should thus dramatically facilitate the development of transgenic mice expressing a conditional suicide gene.

Erythema multiforme (EM) is a hypersensitivity reaction that occurs mainly after exposure to certain medications or in the setting of infection, most commonly that due to herpes simplex virus. Rare cases of EM have been reported after allergic contact dermatitis due to various substances. There has been one case in the literature of EM following Rhus contact dermatitis. We report three patients who developed EM after allergic contact dermatitis due to poison ivy. In all three patients, targetoid lesions developed primarily on the palms and soles, either after a brief course of prednisone or during its taper. Two of the patients have had more than one episode of EM after poison ivy dermatitis. Although EM has been described after allergic contact dermatitis due to a variety of antigens (nickel being the most common), there is only one report in the literature of EM following Rhus contact dermatitis. Given the prevalence of allergic contact dermatitis due to poison ivy, this may be an under-reported complication.

Objectives: The echocardiographic contrast-enhancing effects and safety profile of ALBUNEX (a suspension of air-filled albumin microspheres) were compared with the new contrast agent OPTISON (formerly FS069: a suspension of albumin microspheres containing the gas perfluoropropane) in 203 patients with inadequate noncontrast echocardiograms., Background: The efficacy of ALBUNEX has been limited by its short duration of action. By using perfluoropropane instead of air within the microsphere, its duration of action is increased., Methods: Each patient received ALBUNEX (0.8 and 0.22 mL/kg) and OPTISON (0.2, 0.5, 3.0, and 5.0 mL) on separate days a minimum of 48 hours apart. Echocardiograms were evaluated for increase in left ventricular (LV) endocardial border length, degree of LV opacification, number of LV endocardial border segments visualized, conversion from a nondiagnostic to a diagnostic echocardiogram, and duration of contrast enhancement. A thorough safety evaluation was conducted., Results: Compared with ALBUNEX, OPTISON more significantly improved every measure of contrast enhancement. OPTISON increased well-visualized LV endocardial border length by 6.0+/-5.1, 6.9+/-5.4, 7.5+/-4.7, and 7.6+/-4.8 cm, respectively, for each of the four doses, compared with only 2.2+/-4.5 and 3.4+/-4.6 cm, respectively, for the two ALBUNEX doses (p < 0.001). 100% LV opacification was achieved in 61%, 73%, 87%, and 87% of the patients with the four doses of OPTISON, but in only 16% and 36% of the patients with the two ALBUNEX doses (p < 0.001). Conversion of nondiagnostic to diagnostic echocardiograms with contrast occurred in 74% of patients with the optimal dose of OPTISON (3.0 mL) compared with only 26% with the optimal dose of ALBUNEX (0.22 mL/kg) (p < 0.001). The duration of contrast effect was also significantly greater with OPTISON than with ALBUNEX. In a subset of patients with potentially poor transpulmonary transit of contrast (patients with chronic lung disease or dilated cardiomyopathy), OPTISON more significantly improved the same measures of contrast enhancement compared with ALBUNEX and did so to the same extent as in the overall population. Side effects were similar and transient with the two agents., Conclusion: OPTISON appears to be a safe, well-tolerated echocardiographic contrast agent that is superior to ALBUNEX.

Chromatin assembly factor I (CAF-I) is a three-subunit histone-binding complex conserved from the yeast Saccharomyces cerevisiae to humans. Yeast cells lacking CAF-I (cacDelta mutants) have defects in heterochromatic gene silencing. In this study, we showed that deletion of HIR genes, which regulate histone gene expression, synergistically reduced gene silencing at telomeres and at the HM loci in cacDelta mutants, although hirDelta mutants had no silencing defects when CAF-I was intact. Therefore, Hir proteins are required for an alternative silencing pathway that becomes important in the absence of CAF-I. Because Hir proteins regulate expression of histone genes, we tested the effects of histone gene deletion and overexpression on telomeric silencing and found that alterations in histone H3 and H4 levels or in core histone stoichiometry reduced silencing in cacDelta mutants but not in wild-type cells. We therefore propose that Hir proteins contribute to silencing indirectly via regulation of histone synthesis. However, deletion of combinations of CAC and HIR genes also affected the growth rate and in some cases caused partial temperature sensitivity, suggesting that global aspects of chromosome function may be affected by the loss of members of both gene families.

Fifty-nine patients undergoing elective major gastrointestinal surgery were entered into a prospective, randomized trial between January 1993 and July 1994 comparing the effectiveness, side effects, and hospital costs of postoperative epidural anesthesia (Group 1, n = 29) and intramuscular narcotic injections (Group 2, n = 30). Epidural catheters were inserted by a team that supervised catheter care and infusion rates in the postoperative period. The nonepidural group received intramuscular injections on a regular basis. Patients filled out visual analog scales to measure levels of pain ( 1 = minimal, 10 = maximal) every eight hours. Patient activity, bowel, and urinary function were recorded by the nursing staff. Control of pain (as measured by the daily average visual analog score) was more effective in Group 1 (P < .001) on postoperative days 1-3 (1.3 vs 3.6 on day 1, 0.7 vs 2.6 on day 2, 0.9 vs 3 on day 3). There was no significant difference in mean values between groups 1 and 2 with respect to first ambulation on the hospital ward, onset of liquid diet, intake of solid food, first spontaneous voiding, first bowel movement, length of hospitalization, or charge of hospitalization ($13,439 +/- 7,452 vs $11,821 +/- 6,630). We conclude that epidural anesthesia significantly lessens incisional pain following major elective lower gastrointestinal surgery when compared to analgesic injections alone. However, while not statistically significant, the overall charge was increased by 14% in the epidural group. This finding should be examined in light of the relatively low pain level in patients receiving narcotic injections alone.

Objectives: This study was performed to compare the safety and efficacy of intravenous 2% dodecafluoropentane (DDFP) emulsion (EchoGen) with that of active control (sonicated human albumin [Albunex]) for left ventricular (LV) cavity opacification in adult patients with a suboptimal echocardiogram., Background: The development of new fluorocarbon-based echocardiographic contrast agents such as DDFP has allowed opacification of the left ventricle after peripheral venous injection. We hypothesized that DDFP was clinically superior to the Food and Drug Administration-approved active control., Methods: This was a Phase III, multicenter, single-blind, active controlled trial. Sequential intravenous injections of active control and DDFP were given 30 min apart to 254 patients with a suboptimal echocardiogram, defined as one in which the endocardial borders were not visible in at least two segments in either the apical two- or four-chamber views. Studies were interpreted in blinded manner by two readers and the investigators., Results: Full or intermediate LV cavity opacification was more frequently observed after DDFP than after active control (78% vs. 31% for reader A; 69% vs. 34% for reader B; 83% vs. 55% for the investigators, p < 0.0001). LV cavity opacification scores were higher with DDFP (2.0 to 2.5 vs. 1.1 to 1.5, p < 0.0001). Endocardial border delineation was improved by DDFP in 88% of patients versus 45% with active control (p < 0.001). Similar improvement was seen for duration of contrast effect, salvage of suboptimal echocardiograms, diagnostic confidence and potential to affect patient management. There was no difference between agents in the number of patients with adverse events attributed to the test agent (9% for DDFP vs. 6% for active control, p = 0.92)., Conclusions: This Phase III multicenter trial demonstrates that DDFP is superior to sonicated human albumin for LV cavity opacification, endocardial border definition, duration of effect, salvage of suboptimal echocardiograms, diagnostic confidence and potential to influence patient management. The two agents had similar safety profiles.

We have identified three distinct populations of mouse lymph node dendritic cells (DC) that differ in their capacity to uptake Ag delivered by different routes, and in their dynamics. The "I-DCs" are large cells that resemble the interdigitating cells and have a mature phenotype and a slow turnover. They derive from the regional tissues. The "sm-DCs" and "sI-DCs" are smaller (hence s-DC), have a more immature phenotype and a rapid turnover. The sI-DC phenotype, including CD8alpha expression suggests a lymphoid-related origin. The sI-DC population is expanded 100-fold after an in vivo flt3 ligand treatment. The sm-DC phenotype suggests a myeloid-related origin. Interestingly, sm-DCs can acquire i.v. injected macromolecules in less than 30 min after injection. They may, therefore, play an important role in the immune response against blood Ags.

Visceral artery aneurysms are uncommon lesions that are rarely identified in the absence of symptoms. Between February 1972 and April 1992, nine patients (5 men and 4 women) with rupture of visceral artery aneurysms were treated. The average age was 62 years old (range 39 to 86 years old). The arteries involved were the splenic (4), the common hepatic (2), the left hepatic (1), the celiac (1), and the superior mesenteric (SMA) (1). No ruptured renal artery aneurysm was identified. Six patients presented with abdominal distension, pain, and hemodynamic instability. Three patients had recurrent gastrointestinal bleeding with erosion into the duodenum, the common bile duct or the pancreatic duct. All three had unnecessary gastrointestinal operations despite preoperative (2 patients) or intraoperative (1 patient) identification of a visceral artery aneurysm. One patient with an SMA aneurysm had ligation and bypass. Three patients with splenic artery aneurysms had splenectomy. The remaining five patients had either ligation or resection without arterial reconstruction. No end-organ dysfunction was identified. There was one death (11%) due to the SMA aneurysm. Pathological findings in four patients were cystic medial necrosis, diffuse deficiency of the internal elastic lamina, fibromuscular dysplasia, and atherosclerosis, respectively. The remainder were thought to be due to atherosclerosis on gross examination. Rupture of visceral artery aneurysms occurs infrequently and can be treated by simple ligation in most cases. Recognition that rupture of splanchnic arterial aneurysms into adjacent viscera can cause recurrent gastrointestinal bleeding may prevent both substantial delays in diagnosis and inappropriate therapy.

Alloreactive T cells present in a bone marrow transplant are responsible for graft-versus-host disease (GVHD), but their depletion is associated with impaired engraftment, immunosuppression, and loss of the graft-versus-leukemia effect. We developed a therapeutic strategy against GVHD based on the selective destruction of these alloreactive T cells, while preserving a competent T-cell pool of donor origin. We generated transgenic mice expressing in their T lymphocytes the Herpes simplex type 1 thymidine kinase (TK) suicide gene that allows the destruction of dividing T cells by a ganciclovir treatment. T cells expressing the TK transgene were used to generate GVHD in irradiated bone marrow grafted mice. We show that a short 7-day ganciclovir treatment, initiated at the time of bone marrow transplantation, efficiently prevented GVHD in mice receiving TK-expressing T cells. These mice were healthy and had a normal survival. They maintained a T-cell pool of donor origin that responded normally to in vitro stimulation with mitogens or third party alloantigens, but were tolerant to recipient alloantigens. Our experimental system provides the proof of concept for a therapeutic strategy of GVHD prevention using genetically engineered T cells.

Objectives: This study sought to assess the long-term prognostic utility of dobutamine stress echocardiography in predicting fatal and nonfatal cardiac events., Background: Although dobutamine stress echocardiography has improved sensitivity and specificity for detection of coronary artery disease, little is known of its predictive value for long-term cardiac events. Therefore, we followed up 120 consecutive patients who underwent dobutamine echocardiography for suspected coronary disease from March 1989 to August 1991., Methods: All patients presenting for coronary angiography for chest pain were eligible for recruitment. Follow-up was 100% complete at 5 years (range 3.0 to 6.1). Cardiac events were defined as cardiac death or nonfatal myocardial infarction or the need for coronary revascularization (coronary angioplasty or bypass surgery)., Results: Positive (n = 78) and negative (n = 42) dobutamine test groups differed in their rates of coronary artery bypass graft surgery (37.2% vs. 9.5%, p < 0.001, respectively) and mortality. Of 26 total deaths, 22 occurred in the group with positive dobutamine test results (28% vs. 9.5%, p < 0.018); all 7 cardiac deaths occurred in this group as well (9% vs. 0%, p < 0.045). By multivariate regression analysis, positive results on dobutamine echocardiography remained independently predictive of future cardiac death after left ventricular ejection fraction and other clinical variables were accounted for., Conclusions: A positive finding on dobutamine echocardiography is an independent predictor of long-term cardiac mortality, whereas a negative finding confers a significantly reduced likelihood of cardiac death as much as 5 years from initial testing. We conclude that dobutamine stress echocardiography can be used to predict which patients with suspected coronary artery disease are at low risk for cardiac death and do not require concurrent nuclear or invasive testing.

Smooth-muscle cell proliferation in response to arterial injury represents an important etiologic factor in restenosis after angioplasty. Tyrphostin-47, a protein tyrosine kinase inhibitor, inhibits smooth-muscle cell proliferation in vitro. In this study tyrphostin-47 was incorporated into matrixes to determine whether prolonged local delivery would result in a reduction of neointimal proliferation after arterial injury in a rat carotid balloon-injury model. A polymer matrix (polylactic polyglycolic acid copolymer and pluronic gel F-127, mean matrix weight 7.83 +/- 0.39 mg) was loaded with tyrphostin-47 (25% w/w). Release studies demonstrated delivery of 11% of the incorporated drug over a 21-day release period. In cell culture, tyrphostin-47 released from the polymer matrix produced a reduction in smooth-muscle cell proliferation (p < 0.0007). Balloon denudation injury of the left common carotid artery of 34 animals was performed. In 12 animals, polymer matrixes containing tyrphostin-47 were wrapped around the injured arteries to provide prolonged drug delivery (estimated dosage 28 micrograms/kg/24 hr); in 10 animals a polymer matrix without tyrphostin-47 was implanted; and in 12 animals only balloon injury was performed. The mean neointimal cross-sectional areas, luminal areas, and intima/media ratios were not significantly different among animals receiving local treatment with tyrphostin-47, sham polymer after injury, or balloon injury without polymer implantation. We conclude that despite inhibition of smooth-muscle cell proliferation by tyrphostin-47 in vitro, sustained local delivery of this tyrosine kinase inhibitor does not result in a reduction of neointimal proliferation in the rat carotid injury model.

Background: Telemedicine emerged in the 1950's and declined during the 1970s and 1980s. Its reemergence in the 1990s generally tracks communications technological advances. Though its major applications have traditionally been confined to rural and under-served areas, telemedicine's application grows on a nearly daily basis. Broadly defined, telemedicine describes the transfer of medical data over facsimile or telephone and video conferencing. Though traditionally applied to patient care, it is increasingly being employed in the area of physician education. The Florida Medical Association's computer CME developments are one example.

Purpose: This article reviews our experience with internal carotid artery dissection (ICAD), evaluates the usefulness of Duplex scanning in diagnosis, provides current recommendations for treatment, and better defines long-term prognosis., Methods: The records from 1976 to 1995 of 24 patients who had 28 ICAD were reviewed. All diagnoses were confirmed by arteriography. Presenting symptoms, diagnostic tests, clinical management, and outcome were examined., Results: Nine patients had visual symptoms or headache, 10 had transient focal neurologic symptoms (TIA), and five had stroke. Five of the 19 who had visual symptoms or TIA had a stroke before the diagnosis of ICAD. Seventeen patients who had 19 ICAD underwent a Duplex scan at the time of presentation. Duplex scan identified 18 arterial abnormalities consistent with ICAD (sensitivity, 95%). Three patients died from stroke during the initial hospitalization. Of the 21 who survived, 12 were treated with anticoagulation therapy, six with aspirin, and three with aspirin and anticoagulation therapy. None of the 21 patients had a subsequent stroke. Six patients subsequently had an operation for residual occlusive disease or aneurysm. The mean duration of follow-up was 9.3 years. Two patients developed contralateral ICAD. During follow-up, 19 arteries were studied with Duplex scan, and seven had no residual evidence of ICAD., Conclusions: Patients who have ICAD often have prodromal symptoms before stroke. If diagnosed early, treatment with anticoagulation may prevent stroke. Duplex scans are accurate for defining carotid abnormalities consistent with ICAD and for indicating the need for arteriography. Patients should undergo a follow-up Duplex scan to identify contralateral ICAD.

Objectives: This study sought to determine the efficacy and safety of arbutamine echocardiography in inducing myocardial ischemia and detecting coronary artery disease., Background: Exercise and pharmacologic stress echocardiography are clinically accepted techniques for detecting coronary artery disease. Arbutamine is a new synthetic beta-adrenoceptor agonist developed specifically as a stress agent. Arbutamine is delivered by a new computerized drug delivery device that adjusts the rate of drug infusion according to the patient's heart rate response during stress testing., Methods: The sensitivity of arbutamine echocardiography was determined in 143 patients who had coronary artery disease documented by coronary angiography. A subset of these patients (n = 114) also underwent exercise echocardiography. The specificity, or normalcy, of arbutamine echocardiography was determined in 54 patients considered to have a low likelihood of coronary artery disease., Results: Among those patients who had both stress test results, the incidence of inducing myocardial ischemia (new or worsening wall motion abnormalities) was 79% (95% confidence interval [CI] 69% to 86%, n = 98) for arbutamine and 77% (95% CI 67% to 85%, n = 98) for exercise echocardiography. The sensitivity of detecting coronary artery disease (ischemia or rest wall motion abnormality) was 87% (95% CI 79% to 93%, n = 101) for arbutamine and 83% (95% CI 74% to 90%, n = 101) for exercise echocardiography. The specificity (normalcy) of arbutamine echocardiogrpahy was 96% (95% CI 87% to 100%, n = 52). Arbutamine was well tolerated, and there were no serious adverse events., Conclusions: Arbutamine echocardiography is an effective and safe pharmacologic stress test technique for diagnosing or excluding the presence of coronary artery disease. The ability of arbutamine stress to induce myocardial ischemia, detectable by echocardiography, was comparable to that for exercise.

Purpose: This study was designed to determine the natural history of documented diverticulitis that resolves after treatment with intravenous antibiotics and bowel rest in patients under the age of 50., Methods: Records of 40 patients aged 50 or under who were hospitalized with the diagnosis of acute diverticulitis between 1980 and 1984 were reviewed to obtain data regarding how the diagnosis was made. Patients successfully treated with antibiotics were contacted five to nine years after their attack and surveyed via telephone questionnaire about symptoms, recurrent attacks, and surgical interventions., Results: A total of 40 patients were included in the study. Ten patients (25 percent) required surgery during initial admission, and 30 patients were discharged with resolution of their symptoms after treatment with intravenous antibiotics and bowel rest. A five-year to nine-year follow-up was obtained on patients treated medically, one-third of whom underwent operation for diverticulitis during this period, and two-thirds of whom did not require surgery during the follow-up period. All operations were elective with single-stage resections., Conclusion: Based on our data, we do not recommend surgery in this population after a single episode of diverticulitis that resolves after treatment with antibiotics.

Purpose: This study was undertaken to compare repeat percutaneous transluminal angioplasty (rPTA), arterial reconstruction, and noninvasive therapy for treatment of patients with recurrent stenosis after PTA of the superficial femoral or popliteal artery., Methods: From 1983 to 1993, 93 patients were treated for recurrent femoropopliteal stenosis. Indication for treatment was claudication in 72 patients, rest pain in 9, and ischemic ulcer in 12. Thirty-six patients (38%) were treated with arterial bypass, 35 (38%) with rPTA, and 22 (24%) with exercise and medication. Patients were monitored with clinical examination, ankle-brachial indexes, and duplex scanning. Follow-up ranged from 6 to 110 months (mean 42 months)., Results: With life-table analysis, the clinical and hemodynamic success of patients treated with rPTA was 41% at 1 year, 20% at 2 years, and 11% at 3 years. For patients treated with arterial bypass, the primary graft patency rate was 84%, 72%, and 72% at 1, 2, and 3 years, respectively. The secondary graft patency rate was 94%, 88%, and 88% at the same intervals. All patients with patent grafts were symptom free. All 22 patients treated with noninvasive therapy continued to have symptoms, but none required amputation during follow-up (range 6 to 108 months). Overall, patients with claudication did better than those treated for rest pain or an ischemic lesion after either rPTA or arterial bypass, but no other variable was statistically significant in predicting outcome., Conclusions: This study finds that arterial bypass is safe and more effective than rPTA in treating patients with recurrent stenosis. Preoperative evaluation is unable to select patients likely to benefit from rPTA. Repeat PTA should be reserved for patients with limited life expectancy or contraindications to operation.

Risk factors and postoperative complications of 153 diabetics (DM) who underwent an abdominal aortic operation for occlusive disease or an intact aneurysm from 1964 through June, 1988 were compared with 970 nondiabetics (nonDM) who underwent similar operations during the same time period. Heart disease, hypertension, cerebrovascular disease, and renal insufficiency were more prevalent in diabetics. Postoperatively, DM had a statistically significant increase in the incidence of myocardial infarction (DM 5.2%, nonDM 2.1%, P = .0434) and wound infection (DM 2.6%, nonDM 0.6%, P = .0359). The incidence of renal failure (DM 1.3%, nonDM 1.0%), stroke (DM 2.0%, nonDM 0.6%), and death (DM 3.9%, nonDM 2.9%) was higher in diabetics, but the differences were not statistically significant (P = NS). Operative mortality was greater for patients operated on for aneurysm (DM 5.3%, nonDM 3.2%) than for patients operated for occlusive disease (DM 3.3% versus nonDM 2.7%). Diabetics treated with insulin or oral agents had a higher complication rate than diabetics treated with diet alone or nondiabetics (insulin 13.0%, oral 13.4%, diet 4.2%, nonDM 8.6%). This study finds that diabetic patients can undergo an abdominal aortic operation with operative mortality comparable to that of nondiabetics. Diabetics have more postoperative complications than nondiabetics, but only myocardial infarction and wound infection are of statistical significance. Diabetics treated with insulin or oral agents have more complications than do diabetics treated by diet alone or nondiabetics.

We report two patients with left colonic obstruction and one patient with cecal obstruction caused by incarceration in inguinal hernias. None of the patients had colonic malignancies within the hernial sacs. Reduction of the hernias was followed by resolution of the bowel obstruction and successful hernial repair in all patients.

Hemosuccus pancreaticus--blood entering the gastrointestinal tract through the pancreatic duct--is a rare and elusive form of gastrointestinal bleeding. The most common cause is a splenic artery pseudoaneurysm caused by acute or chronic inflammation of the pancreas. We report the case of an 86-year-old woman who had recurrent gastrointestinal bleeding from erosion of an aneurysm of the splenic artery into the pancreatic duct. The lack of associated symptoms, equivocal endoscopic findings, and the rarity of this entity resulted in a delay in diagnosis. Nonresective treatment by ligation of the splenic artery proximal and distal to the aneurysm prevented any additional bleeding. Postoperative technetium sulfur colloid scanning demonstrated normal perfusion of the spleen. Only 16 cases of hemosuccus pancreaticus from primary splenic artery disease have previously been reported in the English-language literature (15 primary aneurysms, one medial disruption without an aneurysm). In contrast to cases caused by inflammatory pseudoaneurysms, splenic artery-pancreatic duct fistulas caused by primary aneurysms of the splenic artery should be treated without pancreatic or splenic resection, either with surgery or by embolization. In elderly patients with recurrent gastrointestinal bleeding of obscure source, the differential diagnosis should include the possibility of a ruptured aneurysm communicating with a viscus.

Purpose: Vascular clamps, vessel loops, and intraluminal occluding devices used to control tibial and pedal vessels can be injurious and may fail to occlude heavily calcified arteries. In an effort to prevent injury to these small arteries, we have investigated the safety and efficacy of thigh pneumatic tourniquet occlusion for distal vascular control during infrapopliteal reconstruction., Methods: During an 18-month period, 88 tibial or pedal arterial reconstructions were performed on 80 patients (mean age 75 years) by the tourniquet technique. Data regarding indications for operation, preoperative evaluation, intraoperative findings, surgical technique, and early outcome were recorded prospectively., Results: Sixty percent of patients were diabetic: 36% insulin dependent and 24% non-insulin dependent. The indications for operation were claudication in 6 (7%), ischemic ulcer in 24 (27%), rest pain in 25 (28%), and gangrene in 33 (38%) patients. Thirty-five percent of operations followed failed ipsilateral infrainguinal reconstructions. The peroneal artery was the target vessel in 38%, anterior tibial in 26%, posterior tibial in 23%, tibioperoneal trunk in 9%, and inframalleolar vessels in 4% of cases. Preoperative analog waveforms and ankle-brachial indexes were used to classify the tibial arteries as compliant, 49%; relatively noncompressible, 30%; and absolutely noncompressible, 9%. Twelve percent had no Doppler flow at the ankle level. At operation 36 of the target arteries (41%) had mural calcification. Tourniquet pressures of 200 to 400 mm Hg (mode 250 mm Hg) were applied from 13 to 55 minutes (mean 27.1 +/- 9.1 minutes). All patients were given systemic anticoagulants. In 19 limbs (22%) the tourniquet was used to occlude a patent superficial femoral artery above the proximal (inflow) anastomosis to either the superficial femoral artery (8%), the above-knee popliteal artery (5%), or the below-knee popliteal artery (9%). Hemostasis was adequate in all cases and no alternative occlusive devices were required. There were no significant complications attributable to the use of the pneumatic tourniquet., Conclusion: Tourniquet occlusion simplifies the infrapopliteal dissection, lessens operating time, improves visualization of the distal anastomosis, and removes the potential for arterial injury to the target vessel. Arterial calcification and noncompressible tibial arteries do not contraindicate the use of thigh tourniquet occlusion. This technique is preferred for all patients undergoing tibial or pedal artery reconstruction.

Acute renal allograft vein thrombosis is a rare but serious complication of renal transplantation. When occurring in the early posttransplant period it is usually associated with surgical complications and often results in the loss of the graft. At later stages, when graft function has stabilized, its development may then be associated with underlying disorders such as glomerulonephritis, immunosuppressive therapy, increased hematocrit, acute rejection, or extension of lower extremity venous thromboses. We report a case of acute allograft dysfunction occurring in the setting of extensive deep vein thrombosis. In our patient, thrombosis in the setting of acute graft tenderness and swelling, anuria, and an increasing creatinine strongly suggest a diagnosis of acute allograft renal vein thrombosis. We describe a successful reversal of acute renal failure through urokinase thrombolysis and review the current literature on the use of thrombolytic agents for the treatment of acute renal allograft vein thrombosis.

From 1964 through 1991 we performed primary closure of the arteriotomy in 1173 patients and patch angioplasty in 506 patients after carotid endarterectomy. The decision to patch was made at the surgeon's discretion. In general a patch was used for small arteries. In the primary closure group 32 patients (2.7%) had a perioperative stroke and in the patch angioplasty group 17 (3.4%) had a stroke. The difference (2.7% vs. 3.4%) was not significant (p < 0.5275, Fisher's exact two-tailed test). A total of 240 arteries were closed with a vein patch and 11 (4.6%) of these patients had a stroke; 266 were closed with a synthetic patch (Dacron, 211; polytetrafluoroethylene, 55) and six of the patients had a stroke (2.3%). The difference in stroke rate between the vein and synthetic patch groups (4.6% vs. 2.3%) was not significant (p < 0.2159). Patch angioplasty cannot be shown to reduce the incidence of perioperative stroke. Late carotid patency was not studied. This study supports a policy of selective patch angioplasty based on arterial size rather than patching all carotid arteries. When a patch is used, we prefer filamentous Dacron as the patch material.

Optimal topical therapy for distal subungual onychomycosis is not available. An open-label study was performed to determine the safety and efficacy of naftifine hydrochloride (Naftin) 1 percent gel in patients with this disorder of the fingers. Ten patients with culture-proven distal subungual onychomycosis were treated twice daily for six months with naftifine hydrochloride 1 percent gel. At monthly intervals, the target nail was trimmed, the nail bed debrided, and global clinical assessment recorded. Following months three, six, and eight (two months after treatment), the target nail underwent evaluation with potassium hydroxide wet mount and fungal culture. After six months of therapy, eight of ten patients showed negative results of fungal culture and eight of ten patients showed clinical improvement. Adverse effects were minimal and included mild peeling in two patients and mild fissuring with transient fingertip numbness in one patient.

Two hundred thirty-four primary total knee prostheses were evaluated with a 45 degrees merchant view to examine patellar position and fixation. Despite a standardized technique for obtaining roentgenographs, patellar position varied with leg position. Overall, 54.7% tracked centrally, 31.2% tilted, and 14.5% displaced. The incidence of these findings was the same whether the patella was domed or congruent. Neither pain scores nor fixation were affected by position. Postoperative tilt and displacement were more common in patellae that were tilted preoperatively. The incidence of postoperative tilt or displacement was not significantly different in knees in which a lateral release was performed. Patellar tilt in some patients seems inevitable despite careful technique because intraoperative tests are static and postoperative function is dynamic. This does not bode well for wear in a metal-backed patella. Tilt caused increased loading at the periphery of the component where most metal-backed prostheses have thin polyethylene.

The effects of admission status, prior abuse, and the frequency and duration of both physical and sexual abuse on measures of suicidality for a sample of 117 hospitalized adolescents were investigated. Having been abused was found to have a significant association with the number of previous suicide attempts and to interact with the variable of admission status in measures of suicide ideation.

The lower extremity complications of 100 consecutive patients who required the placement of an intra-aortic balloon pump (IABP) during a 3-year period were studied. Indications for the IABP included hypotension during cardiac catheterization (33%) or coronary angioplasty (13%), hemodynamic instability after open heart surgery (35%), unstable angina (5%), and cardiac arrest (14%). The incidence of IABP morbidity was 29%. Complications included ischemia (25%), bleeding (2%), lymph fistula (1%), and femoral neuropathy (1%). Twenty patients required 1 or more surgical interventions for lower extremity vascular complications. The majority of patients who underwent operation (70%) had significant pre-existing arterial occlusive disease. Local femoral artery reconstruction or repair was performed in 18 patients. Two patients had adjunctive bypasses. Continued IABP support was required in four patients after treatment of complications. One patient (1%) had an above-knee amputation. Limb ischemia was treated nonoperatively by removal of the IABP in five patients. Color-flow duplex scans were useful in distinguishing hematomas from pseudoaneurysms as well as for assessing femoral artery flow. We conclude that: (1) limb ischemia remains the primary complication of the IABP; (2) pre-insertion documentation of the severity of existing peripheral arterial disease by noninvasive studies may aid in the management of subsequent acute limb ischemia; (3) femoral artery thrombectomy or endarterectomy is usually sufficient for revascularization; and (4) noninvasive color flow studies are an important diagnostic tool in the nonoperative management of limb complications.

Extracellular recordings were made from the isolated goldfish retina during superfusion with various serotonergic agonists and antagonists to determine the effects of these drugs on the maintained activity and response properties of the ganglion cells. Superfusion of the retina with serotonin (25-500 microM) increased the maintained activity of OFF-center ganglion cells and decreased the maintained activity of ON-center ganglion cells. In addition, serotonin also attenuated the excitatory responses to annular stimuli, suggesting a decrease in the strength of surround input to the ganglion cells. The effects of serotonin on OFF-center ganglion cells were mimicked by the nonselective 5-HT1 agonist 5-MeOT and the 5-HT1A receptor agonist 8-OH-DPAT, while only 5-MeOT mimicked the action of serotonin on ON-center ganglion cells. The effects of exogenously applied serotonin on the ganglion cells could be blocked by the mixed 5-HT1/5-HT2 receptor antagonist methysergide but not by the 5-HT2 receptor antagonist mianserin or the dopamine receptor antagonist haloperidol. These results support previous anatomical and biochemical evidence that serotonin functions in a neurotransmitter or neuromodulatory role in the teleost retina and suggest that serotonin may be involved in modulating the maintained activity and surround input to the ganglion cells. The results also indicate that two different types of receptors may mediate the actions of serotonin in the ON and OFF pathways, respectively.

We implanted 112 glutaraldehyde-fixed bovine carotid artery grafts (BioPolyMeric [BPM]) for infrainguinal reconstruction in 107 legs of 98 patients. Indications for surgery were disabling claudication in 28%, rest pain in 33% and tissue loss in 39%. In 32%, BPM bypass followed failed ipsilateral reconstruction. Autologous vein was either absent or inadequate in 60% of cases. BPM was used preferentially over vein in above-knee bypasses. The distal anastomosis was to the above-knee popliteal artery in 40%, to the below-knee popliteal artery in 35%, and to the tibial arteries in 25%. Follow-up was available from one to 25 months, with a mean of nine months. Wound complications developed after 9% of operations, including seven (6%) graft infections. Both patent grafts that became infected were salvaged. Four patients (4%) died within 60 days of surgery due to cardiac complications. Life-table primary and secondary patencies of all grafts were 64% and 65% at one year, and 48% and 62% at two years, respectively. The only factor significantly affecting graft patency was the location of the distal anastomosis (p < .01). Primary patencies at one and two years to the above-knee popliteal artery were 90% and 80%, to the below-knee popliteal artery were 56% and 37%, and to the infrapopliteal arteries were 34% and 26%. Bypass to 16% of extremities resulted in amputation, including 5% that were amputated with patent grafts. No limb loss occurred as a result of operation for claudication. In conclusion, BPM grafts provide early results comparable to saphenous vein above the knee.(ABSTRACT TRUNCATED AT 250 WORDS)

The records of 146 patients 80 years of age or older who underwent 183 carotid endarterectomy operations from 1964 through 1990 were reviewed to determine surgical risk. The indications for operation were asymptomatic patients with carotid stenosis (n = 36); ipsilateral transient ischemic attacks (n = 46); ipsilateral stroke (n = 28); ipsilateral retinal embolus (n = 15); nonlateralizing symptoms (n = 40); and asymptomatic side in patients with contralateral symptoms (n = 18). Postoperatively, three patients (1.6% of operations) had a stroke with a residual deficit and three (1.6%) died. All deaths were from myocardial infarction. For comparison, during the same time period, the combined stroke with residual deficit and death rate for patients less than 80 operated upon for similar indications was 3.5%. Since 80-year-old patients have a life expectancy of at least five years, the authors conclude that elderly patients should be evaluated for carotid endarterectomy using criteria similar to that used for younger patients.

Isolated dissection of a peripheral artery is a rare event. Only 11 reports exist in the literature of dissection of the superior mesenteric artery, most of which have been fatal. This is the first documented case of the successful treatment of an acute ischemic event caused by a superior mesenteric artery dissection. In addition, the new technique of right gastroepiploic artery-to-superior mesenteric artery bypass is introduced as a satisfactory method of revascularization.

Onychomycosis is the most frequent cause of nail diseases. An open-label study has been conducted to evaluate the safety and efficacy of Fungoid Tincture, a topical antifungal agent approved by the Food and Drug Administration for the treatment of onychomycosis of the toes. Ten patients with culture-proven distal subungual onychomycosis were treated twice daily for twelve months with topical Fungoid Tincture. Another ten patients with the same condition were treated with the vehicle alone. At monthly intervals, the target nail was trimmed, the nail bed debrided, and global clinical assessment recorded. After twelve months of therapy, all patients applying Fungoid Tincture showed negative findings on fungal culture. The vehicle alone benefitted several patients, and may have antifungal activity. Adverse effects were minimal, with mild peeling occurring in seven patients and erythema noted in one.