The Challenges of Distinguishing Different Causes of TMA in a Pregnant Kidney Transplant Recipient.

Thrombotic microangiopathy (TMA) reflects a syndrome of endothelial injury characterised by microangiopathic haemolytic anaemia (nonimmune), thrombocytopenia, and often end-organ dysfunction. TMA disorders are well-recognised in kidney transplant recipients, often due to an underlying genetic predisposition related to complement dysregulation, or de novo due to infection, immunosuppression toxicity, or antibody-mediated rejection. In pregnancy, TMA disorders are most commonly due to severe pre-eclampsia or HELLP, but may also be due to thrombotic thrombocytopenic purpura (TTP) or complement-mediated (atypical) haemolytic uremic syndrome (aHUS). Complement dysregulation is being recognised as playing a role in the development of preeclampsia and HELLP syndrome in addition to aHUS. Due to overlapping clinical and laboratory features, diagnosis can be difficult and delays in treatment can be life-threatening for both mother and fetus. This report describes a 32 year-old female who had two successive wanted pregnancies. The first pregnancy was terminated at 22 weeks gestation due to presumed severe preeclampsia and fetal growth restriction in the context of known chronic kidney failure due to reflux nephropathy. A living-related kidney transplant was performed to improve the chances of pregnancy resulting in a live birth. A subsequent pregnancy was complicated by progressive kidney impairment and hypertension at 22 weeks gestation. Kidney biopsy showed TMA, but the etiology was unclear. This report highlights the diagnostic dilemma of TMA in a pregnant kidney transplant recipient and a role for the anti-C5 terminal complement blockade monoclonal antibody eculizumab, in pregnancy-associated TMA, especially at a peri-viable gestation.

Hearing screening for school children: comparison of low-cost, computer-based and conventional audiometry.

BACKGROUND: There is a need to develop affordable but effective audiometric screening equipment, particularly for use in low-income countries. With advances in computer technology, low-cost computer-based audiometer software has been developed. However, the efficacy of computer-based audiometers in hearing screening and diagnostic assessment requires investigation. The purpose of this study was to evaluate the accuracy of a low-cost, computer-based audiometric system in a school-based hearing screening programme. METHODS: Eighty children were screened using the computer-based audiometer and with a conventional pure tone screening audiometer. Overall refer rates, as well as frequency and age effects on the accuracy of the computer-based audiometer, were considered. RESULTS: There was a significant relationship between the low-cost, computer-based audiometer and a conventional pure tone audiometer when a 40 dBHL refer criterion was used in school hearing screening and when test results at 500 Hz were excluded from analysis. However, background noise effects and software limitations in the computer-based system had major adverse effects on screening performance. CONCLUSIONS: The study results and preliminary practical experience with the system suggest that, with further software and hardware improvements, a low-cost, computer-based system may well be feasible for routine school screening in developing countries.

The anharmonic potential energy surface of methyl fluoride.

A large experimental spectroscopic data set sensitive to the cubic anharmonic potential energy surface (PES) of methyl fluoride has been compiled from the literature for six symmetric and asymmetric top isotopomers of methyl fluoride: 12CH3F, 13CH3FF, 12CD3F, 13CD3F, 12CHD2F and 12CH2DF. This empirical data set has been used to critically assess the best available literature ab initio cubic force field and various 'improved' theoretical force fields. A perturbation-resonance approach to the calculation of the observables from the force constants has been utilized and existing PESs were found to reproduce the data poorly. The careful treatment required for the correct theoretical reproduction of empirical spectroscopic constants arising from highly correlated least-squares fits to the original data is discussed. A new fit to the data has been performed (optimising 19 of the 38 cubic force constants) resulting in a much improved PES. The latter has been used to predict currently unknown spectroscopic constants for the least well-characterised isotopomer 12CH2DF. The prospects for a future empirical determination of the complete cubic force field of methyl fluoride are discussed and new data most likely to yield new information on the PES identified.

Fourier Transform Infrared Spectra of CH(2)DF: The nu(5) and nu(6) Bands.

Results of a high-resolution infrared study of the spectroscopy of monodeuterated methyl fluoride, CH(2)DF, are reported for the first time. Spectra ranging from 500 to 3300 cm(-1) have been obtained and cover all the fundamental bands at resolutions down to 0.005 cm(-1). The two lowest energy fundamentals, the nu(5) and nu(6) bands, have been analyzed in detail. Since the molecule has C(s) symmetry, in principle both these bands are AB hybrids, since they belong to the irreducible representation A'. However, it was found that both are almost pure A-type bands. A total of 597 A-type lines of the nu(5) band and 619 A-type lines of the nu(6) band have been assigned. Vibrational and rotational spectroscopic constants have been determined by least-squares fitting to the data. An improved band center for nu(7) is also reported. Copyright 2001 Academic Press.

The General Harmonic Force Field of Methyl Chloride.

The complete general harmonic force field of methyl chloride has been recalculated using the most recent literature frequency, Coriolis zeta, and centrifugal distortion data for (12)CH(3)(35)Cl, (13)CH(3)(35)Cl, (12)CD(3)(35)Cl, (12)CHD(2)(35)Cl, (12)CH(2)D(35)Cl, (12)CH(3)(37)Cl, (12)CD(3)(37)Cl, (12)CHD(2)(37)Cl, (12)CH(2)D(37)Cl, and (13)CH(3)(37)Cl. The anharmonic corrections applied to the observed frequency data are considered to be more realistic than those used hitherto. There is excellent agreement between the fitted force constants and literature high-quality ab initio force fields. The results of the least-squares refinement of the full-harmonic force field is compared with least-squares refinement of only the scale factors for an SCF calculated force field since the latter approach may be useful for larger molecules where more sophisticated calculations are impractical. The results of a refinement of only the scale factors for an MP4 calculated force field are also reported. Copyright 2001 Academic Press.

High-resolution calculations of asteroid impacts into the Venusian atmosphere.

We present results from a number of 2D high-resolution hydrodynamical simulations of asteroids striking the atmosphere of Venus. These cover a wide range of impact parameters (velocity, size, and incidence angle), but the focus is on 2-3 km diameter asteroids, as these are responsible for most of the impact craters on Venus. Asteroids in this size range are disintegrated, ablated, and significantly decelerated by the atmosphere, yet they retain enough impetus to make large craters when they meet the surface. We find that smaller impactors (diameter <1-2 km) are better described by a "pancaking" model in which the impactor is compressed and distorted, while for larger impactors (>2-3 km) fragmentation by mechanical ablation is preferred. The pancaking model has been modified to take into account effects of hydrodynamical instabilities. The general observation that most larger impactors disintegrate by shedding fragments generated from hydrodynamic instabilities spurs us to develop a simple heuristic model of the mechanical ablation of fragments based on the growth rates of Rayleigh-Taylor instabilities. Although in principle the model has many free parameters, most of these have little effect provided that they are chosen reasonably. In practice the range of model behavior can be described with one free parameter. The resulting model reproduces the mass and momentum fluxes rather well, doing so with reasonable values of all physical parameters.

Dexamethasone and enalapril suppress intimal hyperplasia individually but have no synergistic effect.

Vascular injury is associated with complex interactions that lead to development of intimal hyperplasia (IH). We have demonstrated previously that the corticosteroid dexamethasone and the ACE-inhibitor enalapril are effective in suppressing the development of IH. We hypothesize that due to distinctly different pharmacologic mechanisms of action, a synergistic effect would be expected if these agents were given in combination. Forty New Zealand White rabbits underwent balloon catheter denudation of the carotid artery. Animals were divided into four equal treatment groups and received daily intramuscular injections: Group 1, saline; Group 2, enalapril 0.07 mg/kg, Group 3, dexamethasone 0.125 mg/kg; and Group 4, enalapril 0.07 mg/kg plus dexamethasone 0.125 mg/kg. Vessels were harvested at 12 weeks and intimal hyperplasia was measured as a ratio of the absolute area of IH to the normalized area enclosed by the internal elastic lamina (IH/IEL). Mean values for IH/IEL are expressed as a percent (SD): Group 1, 32.31 (14.9); Group 2, 9.47 (2.11); Group 3, 5.40 (4.14); and Group 4, 8.49 (4.27). All treatment groups demonstrated significant suppression of IH compared to the control group (p < 0.01); dexamethasone was more effective than enalapril (p = 0.01). There was no statistical difference in IH suppression between respective agents and the combination group (p > 0.10). Coadministration of dexamethasone and enalapril provides no advantage over single-agent therapy in suppressing the development of IH, suggesting that maximal suppression is obtained with single-agent treatment or that these agents affect IH through a common pathway.

Fluid-percussion brain injury adversely affects control of vascular tone during hemorrhagic shock.

To test the hypothesis that brain injury impairs control of vascular tone during compensation from hemorrhagic shock, Sprague-Dawley rats underwent fluid-percussion brain injury (or sham injury control) followed by a stepwise hemorrhage period to 1/2 baseline mean arterial pressure (1/2 MAP), a shock period holding at 1/2 MAP for 30 min, and a resuscitation period. Aortic blood flow (ABF) was measured and vascular conductance (ABF/MAP) was calculated. No differences occurred between groups during the stepwise hemorrhage period. During the 30 min shock period, controls decreased conductance from .2 +/- .07 to .16 +/- .04 and required repeated additional hemorrhage (3.4 +/- 1.3 cc) to maintain 1/2 MAP. In contrast, brain-injured animals increased conductance from .21 +/- .07 to .24 +/- .06 (p < .05) during the shock period and required repeated fluid replacements (3.0 +/- 1.3 cc lactated Ringer's (LR), p < .05) to maintain 1/2 MAP. Following resuscitation, conductance appropriately increased to .31 +/- .05 in controls but did not change (.25 +/- .04, p < .05) in brain-injured animals. We conclude that brain injury adversely affects control of vascular tone during shock and resuscitation in this model.

Cigarette smoking increases the development of initial hyperplasia after vascular injury.

PURPOSE: Our purpose was to determine whether exposure to cigarette smoke increases the development of intimal hyperplasia (IH) after vascular injury. METHODS: Sixteen adult male Sprague-Dawley rats underwent standardized balloon catheter injury of the left common carotid artery. For 4 weeks before and 4 weeks after injury, animals in the experimental group (n=8) were exposed to cigarette smoke with an automated vacuum pump device. Animals in the control group (n=8) were restrained in the smoking device for an identical amount of time and underwent arterial injury at 4 vivo, prepared as histologic cross sections, and stained for elastin. IH was measured by planimetry and is reported both as the absolute area of IH and as the ratio (IH/IEL) of the absolute area of IH to the normalized area enclosed by the internal elastic lamina (expressed as a percent). RESULTS: The absolute area of IH was 2.09 +/- 0.34 for the experimental group compared with 0.94 +/- 0.25 for the control group; mean IH/IEL was 43% +/- 7.1% for the experimental group versus 17.7% +/- 4.7% for the control group (p < 0.05, two tailed unpaired t test. CONCLUSIONS: Inhalation of cigarette smoke increases the development of intimal hyperplasia in a rat model of a balloon catheter arterial injury.

Role of surgery in the management of primary lymphoma of the gastrointestinal tract.

The role of surgery in the management of primary gastrointestinal lymphoma remains controversial. We retrospectively reviewed the management and outcome of 107 patients with the diagnosis of gastrointestinal lymphoma treated at the UCLA Medical Center during the period 1956-1990. Sixty-four patients underwent surgical exploration at the UCLA Medical Center; 35 of these underwent resection for cure. Sixteen of these 35 patients received no postoperative adjuvant therapy. Twenty-nine patients underwent palliative or "noncurative" resection. There were five postoperative deaths (mortality rate 8%). The overall morbidity rate was 48% There were 3 perforations in a total of 53 patients receiving multiagent chemotherapy. Five-year actuarial survival was as follows: 59% for curative resection alone, 51% for curative resection plus adjuvant therapy, and 28% for "noncurative" resection (P<0.05). Multivariate analysis revealed that stage of disease (P<0.01) and resection for cure (P<0.05) were independent predictors of survival. These results suggest that patients undergoing resection for cure have improved survival. The apparent low risk of perforation during chemotherapy, along with the considerable risk of morbidity and mortality associated with operation, suggests that a policy of debulking large tumors prior to chemotherapy is unwarranted.

A new Canadian health care initiative in Tanzania.

One of the main conclusions of the World Bank's World Development Report 1993--Investing in Health was that equitable access to a package of essential clinical and public health services could significantly reduce the overall burden of disease in low-income countries. The report argued that more rational and effective decisions with regard to the allocation of limited resources could be made on the basis of burden-of-disease and cost-effectiveness analyses. In collaboration with the Canadian International Development Agency and several other organizations, the International Development Research Centre has developed the Essential Health Interventions Project to test the feasibility of this approach in a few districts in Tanzania. Outcome assessment wil focus on improved planning at the district level and on changes to the health status of the study population.

As Canadians butt out, the developing world lights up.

Although rates of tobacco smoking in Canada have dropped dramatically over the last 30 years this is not a global trend. For every tonne of tobacco that Canadian adults gave up between 1970 and 1990, aggressive marketing by multinational tobacco companies has ensured that an additional 20 tonnes is now consumed in developing countries. The authors describe the dilemma faced by policymakers in their efforts to control the epidemic of tobacco smoking in the developing world: although tobacco consumption leads to increased rates of mortality and morbidity and lost productivity, its production creates employment, generates tax revenue and earns foreign exchange. Canadian experience has proved that trends in tobacco consumption can be reversed through policies that address not only health issues but also economic social and agricultural concerns. The authors propose a framework for harnessing expertise in the service of worldwide tobacco control.

Pharmacologic suppression of intimal hyperplasia: a dose-response suppression by enalapril.

Intimal hyperplasia is an exaggerated proliferative response to arterial intimal injury. A successful means of limiting this hyperplastic response would significantly improve patency rates of vascular reconstruction. Angiotensin-converting enzyme (ACE) inhibitors decrease the proliferation and synthetic function of vascular smooth muscle cells in vitro, which have been implicated in the production of intimal hyperplasia. We performed a dose-response study of enalapril to assess the level at which maximal suppression of intimal hyperplasia occurs. Seventy male Sprague-Dawley rats weighing 250-300 grams underwent standardized carotid artery balloon catheter endothelial denudation to induce intimal hyperplasia. Six groups of ten animals each were treated with daily intramuscular injections of one of the following doses of enalapril (mg/kg): 0.025, 0.050, 0.075, 0.100, 0.125, and 0.150. A control group (n = 10) was treated with saline. Injections were started two days before injury and continued for 4 weeks, at which time the injured arteries were pressure-fixed in vivo and harvested. EVG-stained histologic cross-sections were measured by planimetry to determine the amount of intimal hyperplasia, which was calculated as the percentage of the arterial lumen replaced by the lesion. Enalapril suppresses the development of intimal hyperplasia in a dose-responsive manner in this model. No further suppression is achieved above a dose of 0.125 mg/kg.

Carotid-subclavian bypass for brachiocephalic occlusive disease. Choice of conduit and long-term follow-up.

BACKGROUND AND PURPOSE: Atherosclerotic disease of the proximal brachiocephalic circulation may produce disabling symptoms referable to cerebral or upper extremity hypoperfusion and embolization. Bypass of occlusive lesions can provide durable relief of symptoms with minimal complications. The ideal conduit for carotid-to-subclavian and subclavian-to-carotid bypass remains controversial, and it is not clear whether the outflow vessel influences patency and survival. METHODS: We performed a retrospective analysis of 60 consecutive carotid-to-subclavian and subclavian-to-carotid bypass procedures. Occlusive lesions were documented preoperatively by arteriography. Patency was determined during follow-up by ultrasound or duplex examination. Actuarial patency, symptom-free survival, and overall survival rates were calculated by the life-table method and analyzed by log-rank test. RESULTS: Arterial transposition demonstrated the highest long-term patency rate (100.0 +/- 0.0%). Polytetrafluoroethylene grafts demonstrated the highest bypass graft patency rate (95.2 +/- 4.6%), followed by Dacron grafts (83.9 +/- 10.5%) and saphenous vein grafts (64.8 +/- 16.5%). Symptom-free survival paralleled patency rates, but these differences did not achieve statistical significance. While there were no differences in patency or symptom-free survival by outflow vessel, the overall survival of patients with common carotid lesions was significantly lower than that of patients with subclavian lesions (62.7 +/- 12.8% versus 100.0 +/- 0.0%; P < .05). CONCLUSIONS: The outflow vessel does not affect long-term patency in carotid and subclavian bypass procedures; however, patients with common carotid disease demonstrate significantly poorer long-term survival. Transposition results in superior long-term patency, with a trend toward lower results for synthetic grafts and relatively poor results for autogenous vein grafts.

Cigarette smoking accelerates carotid artery intimal hyperplasia in a dose-dependent manner.

BACKGROUND AND PURPOSE: Intimal hyperplasia is the single most important cause of early restenosis after carotid endarterectomy. Cigarette smoking is an independent risk factor associated with peripheral vascular disease and cerebrovascular accidents. We undertook a dose-response experiment to determine the effect of cigarette smoke on development of intimal hyperplasia in a rat carotid artery intimal injury model. METHODS: Seventy-two rats were divided into six equal groups and underwent standardized balloon injury to the carotid artery. Each group received 0 (controls), 1, 2, 3, 6, or 8 cigarettes per day for 4 weeks. Resultant intimal hyperplasia was expressed as a percentage of original lumen replaced by intimal hyperplasia. RESULTS: Percent intimal hyperplasia development (+/- SD) was as follows: controls (0 cigarettes per day), 17.7 +/- 13.2; 1 cigarette per day, 22.8 +/- 15.0; 2 cigarettes per day, 20.0 +/- 14.7; 3 cigarettes per day, 19.2 +/- 12.1; 6 cigarettes per day, 43.5 +/- 15.5; and 8 cigarettes per day, 36.7 +/- 9.8. Six and 8 cigarettes per day significantly increased the development of intimal hyperplasia after intimal injury (P < .01). CONCLUSIONS: High-dose cigarette smoke accelerates development of intimal hyperplasia and may pose a significant risk factor in developing carotid restenosis.

Elevated levels of soluble ICAM-1 correlate with the development of multiple organ failure in severely injured trauma patients.

Serum levels of interleukin-6, interleukin-8, the soluble receptor for tumor necrosis factor (sTNFr), and the soluble receptor for intercellular adhesion molecule-1 (sICAM-1) were measured serially in a series of 13 severely injured trauma patients to determine if any of these elements of the inflammatory response are predictive of multiple organ failure (MOF). Six of the 13 patients developed MOF as determined by a MOF scoring system. At the completion of resuscitation (when oxygen delivery and consumption were maximized) sICAM-1 levels were significantly higher in MOF patients before the development of clinical evidence of organ failure (700 +/- 67 ng/mL) compared with non-MOF patients (302 +/- 18 ng/mL). There was a significant correlation between the absolute level of sICAM-1 at the time of resuscitation and the severity of subsequent MOF. This finding suggests that leukocyte-endothelial cell interactions are upregulated immediately after injury and may be implicated in the end-organ injury that leads to MOF.

Evaluation of the prognostic significance of the site of origin of cutaneous melanoma.

The prognostic significance of the BANS region (Back, Arms, Neck, Scalp) in primary cutaneous melanoma remains controversial. We hypothesized that the different anatomic sites of the BANS region may have different prognostic significance. As the anatomic areas examined have varied between reports on BANS or head and neck melanomas, these differences could explain the lack of consistent findings. Between 1971-1990 more than 5000 patients with Stage I (n = 2576) and Stage II (n = 852) cutaneous melanoma were treated at the UCLA Medical Center. Patients were stratified for analysis into the following anatomic categories: scalp, neck, upper back, arm, and other anatomic sites. Initial analysis revealed that Clark's level of invasion, tumor thickness, gender, and number of positive nodes were predictive of survival. Controlling for these variables, the impact of the site of origin on prognosis was evaluated. Five-year actuarial survival in Stage I patients was as follows: scalp--80 per cent, neck--92 per cent, upper back--90 per cent, arm--94 per cent, all others--89 per cent. There were no significant survival differences between these groups, although the poorer survival for scalp primaries approached statistical significance (P = 0.084). In Stage II disease, however, marked survival differences were noted between anatomic sites. median survival for Stage II patients was as follows: scalp--25 months, neck--28 months, upper back--38 months, arm--75 months, all others--67 months (P = 0.005). These results indicate that anatomic site of origin does affect prognosis in patients with nodal metastases.

Cytokine, complement, and endotoxin profiles associated with the development of the adult respiratory distress syndrome after severe injury.

OBJECTIVE: The adult respiratory distress syndrome (ARDS) is a frequent complication after severe accidental trauma. This study examines the hypothesis that increased systemic concentrations of proinflammatory cytokines, endotoxin, or complement fragments may predict the development of ARDS. DESIGN: Prospective, observational study. SETTING: Two Level I university trauma centers. PATIENTS: Fifteen severely injured patients (Injury Severity Score of > or = 25). INTERVENTIONS: Standard emergency department, operating room, and intensive care unit management. MEASUREMENTS AND MAIN RESULTS: Plasma samples were obtained at 4-hr intervals from the time of injury and were assayed for concentrations of endotoxin, tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-6, IL-8, and complement fragments C3a and C4a. Hemodynamic and oxygen metabolism variables also were measured at 4-hr intervals after injury. Seven patients developed ARDS and eight patients did not. The PaO2/FIO2 ratio was significantly decreased in the patients with ARDS compared with non-ARDS patients as early as 4 hrs postinjury, and remained significantly decreased throughout the initial 24 hrs after severe accidental injury. Plasma IL-8, IL-6, C3a, and C4a concentrations were markedly increased starting in the immediate postinjury period in both ARDS and non-ARDS patients, but no significant differences were found between the two groups until 16 hrs after injury when plasma IL-8, C3a, and C4a concentrations became significantly higher in the ARDS group. Neither the ARDS nor non-ARDS patients showed the presence of circulating IL-1 beta, TNF-alpha, or endotoxin at any postinjury time point. CONCLUSIONS: These results demonstrate that measurements of plasma concentrations of proinflammatory cytokines, endotoxin, or complement fragments are not helpful in predicting the development of ARDS after severe accidental injury.

Suppression of intimal hyperplasia in a rabbit model of arterial balloon injury by enalaprilat but not dimethyl sulfoxide.

Intimal hyperplasia appears to result from the deposition of collagen and matrix by medial myofibroblasts, which are stimulated in response to vascular injury. We hypothesized that pharmacologic inhibitors of fibroblast proliferation would suppress the development of intimal hyperplasia. We evaluated the effect of two agents known to inhibit fibroblast proliferation in vitro: enalaprilat, an angiotensin-converting enzyme (ACE) inhibitor, and dimethyl sulfoxide (DMSO), an organic solvent. Thirty-five New Zealand white rabbits underwent standardized balloon catheter injury of the left common carotid artery. Experimental groups received daily intramuscular injections of the following: group I (n = 15), saline solution; group II (n = 10), 0.07 mg/kg enalaprilat; and group III (n = 10), 2 ml/kg of a 25% by weight DMSO solution. Injections were started 1 day prior to injury and continued 5 days a week for 8 weeks. Carotid arteries were perfusion-fixed at 12 weeks and cross-sectioned for measurement by planimetry. Intimal hyperplasia was measured as the ratio of the absolute area of intimal hyperplasia to the normalized area enclosed by the internal elastic lamina (IH/IEL) and was expressed as a percent. Mean values for IH/IEL were as follows: group I (control), 20.6 +/- 2.3%; group II (enalaprilat), 9.5 +/- 0.7%; and group III (DMSO), 17.6 +/- 2.6%. Enalaprilat-treated animals demonstrated a statistically significant suppression of intimal hyperplasia compared with controls (p < 0.01, ANOVA, Student's t test), whereas the DMSO-treated group did not. We conclude that enalaprilat is effective in suppressing the development of intimal hyperplasia in this model of arterial injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous postoperative intra-arterial urokinase infusion in the treatment of no reflow following revascularization of the acutely ischemic limb.

The loss of distal tissue perfusion sufficient for limb salvage following restoration of inflow to an acutely ischemic extremity has been referred to as the "no-reflow" phenomenon. We hypothesized that patients with no reflow and limb-threat ischemia might benefit from prolonged postoperative intra-arterial infusion of the thrombolytic agent urokinase (UK). Twelve patients with arteriographic and clinical evidence of no reflow following a lower extremity arterial thrombectomy and/or bypass procedure were treated with a continuous intra-arterial UK infusion in the immediate postoperative period. The mean duration of UK infusion was 47 hours (range 15 to 112 hours). The mean rate of infusion was 58,000 units/hr (range 30,000 to 100,000 units/hr). Seven patients required transfusion for bleeding from the treated extremity (mean 3.4 units packed cells) and one required reoperation for a groin hematoma. Plasma fibrinogen levels remained within the normal range in all patients, and no systemic bleeding complications were encountered. The intra-arterial UK infusion resulted in limb salvage in 7 of 12 patients. Six patients have viable, functional extremities at a mean follow-up interval of 24.9 months (range 6.4 to 49.7 months). One patient required below-knee amputation 6 months after treatment for progressive ischemia. The other five patients required below-knee amputation during the same hospitalization after UK failed to restore distal perfusion. The postoperative period is widely considered to be a contraindication to thrombolytic therapy. Our experience indicates that while UK may cause bleeding from the treated extremity, which in some cases requires transfusion, there is no evidence of systemic fibrinolysis or systemic hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)