Functional mucous layer and healing of proximal colonic anastomoses in an experimental model.

BACKGROUND: Anastomotic leakage (AL) is the most dreaded complication after colorectal surgery, causing high morbidity and mortality. Mucus is a first line of defence against external factors in the gastrointestinal tract. In this study, the structural mucus protein Muc2 was depleted in genetically engineered mice and the effect on healing of colonic anastomoses studied in an experimental model. METHODS: Mice of different Muc2 genotypes were used in a proximal colonic AL model. Tissues were scored histologically for inflammation, bacterial translocation was determined by quantitative PCR of bacterial 16S ribosomal DNA, and epithelial cell damage was determined by assessing serum levels of intestinal fatty acid-binding protein. RESULTS: Of 22 Muc2-deficient (Muc2-/- ) mice, 20 developed AL, compared with seven of 22 control animals (P < 0·001). Control mice showed normal healing, whereas Muc2-/- mice had more inflammation with less collagen deposition and neoangiogenesis. A tendency towards higher bacterial translocation was seen in mesenteric lymph nodes and spleen in Muc2-/- mice. Intestinal fatty acid-binding protein levels were significantly higher in Muc2-/- mice compared with controls (P = 0·011). CONCLUSION: A functional mucous layer facilitates the healing of colonic anastomoses. Clinical relevance Colorectal anastomotic leakage remains the most dreaded complication after colorectal surgery. It is known that the aetiology of anastomotic leakage is multifactorial, and a role is suggested for the interaction between intraluminal content and mucosa. In this murine model of proximal colonic anastomotic leakage, the authors investigated the mucous layer at the intestinal mucosa, as the first line of defence, and found that a normal, functioning mucous layer is essential in the healing process of colonic anastomoses. Further research on anastomotic healing should focus on positively influencing the mucous layer to promote better postoperative recovery.

ICIQ symptom and quality of life instruments measure clinically relevant improvements in women with stress urinary incontinence.

AIMS: To determine whether changes in questionnaire scores on symptoms and condition-specific quality of life reflect clinically relevant improvements in women with stress urinary incontinence (SUI). METHODS: We retrospectively analyzed questionnaires collected during a randomized controlled trial in women with SUI, that received pelvic floor muscle training (PFMT) in two different formats. We included 218 women that answered validated self-assessment questionnaires at baseline and at a 4-month follow-up. We registered changes on two questionnaires, the International Consultation on Incontinence Modular Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) and the Lower Urinary Tract Symptoms Quality of Life (ICIQ-LUTSqol). We compared these score changes to responses from the Patient Global Impression of Improvement (PGI-I) questionnaire. Differences were analyzed with the Spearman rho and one-way-ANOVA. The minimum important difference (MID) was the mean change in score for women that experienced a small improvement. RESULTS: The PGI-I correlated significantly to both the ICIQ-UI SF (r = 0.547, P < 0.0001) and ICIQ-LUTSqol (r = 0.520, P < 0.0001). Thus, larger reductions in symptoms or quality of life scores were associated with greater impressions of improvement. The changes in ICIQ-UI SF and ICIQ-LUTSqol scores were significant across all PGI-I groups from "no change" to "very much improved" (P < 0.05). The MIDs were 2.52 (SD 2.56) for ICIQ-UI SF and 3.71 (SD 4.95) for ICIQ-LUTSqol. CONCLUSIONS: The change in ICIQ-UI SF and ICIQ-LUTSqol scores after PFMT reflected clinically relevant improvements in women with SUI. The MIDs established for this population may facilitate future research, treatment evaluations, and comparisons between studies.

Bovine recto-anal junction squamous epithelial (RSE) cell adhesion assay for studying Escherichia coli O157 adherence.

AIM: To develop a new adherence assay, using cattle recto-anal junction squamous epithelial (RSE) cells, for evaluating bacterial adherence to cells of bovine origin. METHODS AND RESULTS: Proof of concept was demonstrated using the human gastrointestinal pathogen Escherichia coli O157:H7, for which cattle are reservoirs. Adherence assays were conducted using both RSE and HEp-2 cells, in the presence and absence of D+Mannose. E. coli O157 specifically adhered in a type I fimbriae-independent manner to RSE cells in significantly higher numbers and also bound significantly higher numbers of RSE cells than diverse laboratory strains of nonpathogenic E. coli. CONCLUSION: The RSE cell adhesion assay output highly reproducible and interpretable results that compared very well with those obtained using the more extensively used HEp-2 cell adherence assay. SIGNIFICANCE AND IMPACT OF THE STUDY: The RSE cell adhesion assay provides a convenient means of directly defining and evaluating pathogen factors operating at the bovine recto-anal junction. The RSE cell adhesion assay further has the potential for extrapolation to diverse bacteria, including food-borne pathogens that colonize cattle via adherence to this particular anatomical site.

Reconstruction of the atrophic maxilla with interpositional bone grafting/Le Fort I osteotomy and endosteal implants: a 11-16 year follow-up.

A Le Fort I osteotomy and interpositional bone graft in combination with implants was used in the reconstruction of patients with extreme atrophy in their maxillae. Surgery was performed in a two-stage procedure. The patients in this study had conditions with reversed intermaxillary relationships with or without increased vertical intermaxillary distance. The aim of the study was to investigate treatment outcome for patients in a prospective, long-term, follow-up with a mean of 13 years (range 11-16 years), concerning implant survival rate and marginal bone loss adjacent to the surfaces of the implant. The impact of gender and smoking was also investigated. Twenty-six patients were included in the study. Of 167 implants, 24 failed. The implant estimated survival rate was 85% at the end of the follow-up. There was no significant difference between smokers and non-smokers or genders concerning implant survival. Marginal bone loss was 2.5, 2.9, 3.0 and 3.1mm from the implant-abutment junction, after 1, 2, 5 and 10 years, respectively. The bone level stabilised after 2 years. This technique results in good facial morphology, good oral function and aesthetics. All patients are still wearing their original fixed bridges.

Dexamethasone depletes gammadelta T cells and alters the activation state and responsiveness of bovine peripheral blood lymphocyte subpopulations.

Administration of dexamethasone (DEX) to cattle is commonly used in models of stress-induced effects on host defense, including models investigating interactions of microorganisms with their host. Much less is known about the effects of DEX on the adaptive immune response in cattle compared with other species. The objective of the present study was to characterize subsets of circulating lymphocytes in calves before and 48 h after the onset of parenteral DEX treatment. Treatment significantly reduced the overall percentage of circulating lymphocytes and disproportionately depleted the population of gammadeltaTCR(+)/CD8alpha(-) cells. Analysis within the CD8alpha(+) population of T cells revealed that DEX treatment also reduced the CD8alpha(low) subset of gammadeltaT cells coexpressing the activation marker ACT-2(+). By contrast, DEX treatment did not affect the percentage of CD8alpha(low)/CD25(+) cells, indicating that cells with a special activation state were affected. Dexamethasone treatment reduced the number of gammadeltaT cells but increased the percentages of CD14(+) monocytes and activated CD25(+) cells (both CD4(-) and CD4(+)) in peripheral blood mononuclear cell (PBMC) preparations. Although DEX treatment reduced the overall proliferative capacity of PBMC, it enhanced the relative number of proliferating CD4(+) lymphocytes. Lower levels of mRNA for several Th-prototype cytokines (IL-2, IFN-beta, IL-4, transforming growth factor-beta) were detected in short-term PBMC cultures established from DEX-treated calves compared with PBMC cultures from control calves; the amount of il-10 transcripts, however, was unaffected. Results of the study reported here clearly show that DEX treatment does not uniformly suppress the bovine immune system but has differential effects on lymphocyte sub-populations and functions. This information must be considered when using DEX treatment as a bovine stress model.

Amiodarone inhibits thyroidal iodide transport in vitro by a cyclic adenosine 5'-monophosphate- and iodine-independent mechanism.

Thyroid side effects are common in patients treated for cardiac arrhythmias with amiodarone (AM). A major disturbance is inhibited thyroidal radioiodine uptake in AM-induced thyrotoxicosis, which makes 131I therapy ineffective. On the other hand, failure to escape from the Wolff-Chaikoff effect by down-regulation of the sodium/iodide symporter (NIS) is proposed to explain AM-induced hypothyroidism. However, previously no experimental studies on the possible mechanisms have been conducted. We therefore investigated the early effects of AM on thyroidal iodide transport using bicameral chamber cultures of primary pig thyrocytes that reproduce the three tissue compartments (epithelium, lumen, and extrafollicular space) of the gland. AM dose-dependently (1-50 microm) inhibited the TSH-stimulated transepithelial (basal to apical) transport of 125I- by up to 90%. The inhibitory effect was noticed already after 8 h and was further pronounced after 1-4 d, depending on the AM concentration. The intracellularly accumulated 125I- was reduced by perchlorate but not AM, and quantitative real-time RT-PCR revealed no change in the NIS expression in AM-treated cells. Blocking of cAMP degradation with 3-isobutyl-1-methylxanthine or withdrawal of AM reversed AM-induced changes in electrolyte transport but were unable to recover the suppressed 125I- transport. The iodine-free AM analog dronedarone also inhibited 125I- transport to the same extent as AM. The findings indicate that AM blocks thyroidal iodide uptake by reducing the iodide permeability of the apical plasma membrane of the thyroid epithelial cells. The effect is iodine independent and long-lasting and does not involve impaired function of NIS or the TSH receptor/cAMP signaling pathway.

Effect of lifelong iodine supplementation on thyroid 131-I uptake: a decrease in uptake in euthyroid but not hyperthyroid individuals compared to observations 50 years ago.

BACKGROUND: In Sweden, iodine has been added to table salt (10 mg/kg) since 1936; this amount was increased in 1966 to 50 mg/kg. OBJECTIVE: To investigate a euthyroid Swedish population (n = 44, 60-65 years) with its entire lifespan with iodine supplementation as for 24-h 131-I uptake (24 h IU) and thyroid nodularity (thyroid scintigraphy). To compare the euthyroid 24 h IU with uptake of thyrotoxic individuals, and with observations from 1955. METHODS: The 24 h IU was used in euthyroid individuals after oral administration of 0.1 MBq/2.7 microCi radioiodine and imaging of the thyroid gland was carried out using 99mTc-pertechnetate. RESULTS: In 1999-2000, the mean 24 h IU in the euthyroid individuals was 21% (range 11-33%) and the normal (central 95%) reference interval was 14-30%. Scintigraphy suggested multinodular goitre in three euthyroid individuals. In Graves' patients (n = 53, 50-65 years), the mean 24 h IU was 61% (range 29-89%). In 1955, the 24 h IU in euthyroid individuals was higher (38%, range 10-70%), while hyperthyroid patients had uptake values similar to those recorded in the present investigation (mean 62%, range 40-90%). CONCLUSIONS: The population sample studied had to be small for ethical reasons. We conclude that the reference interval for 24 h IU is 14-30% in this population that had spent its entire lifespan with iodine supplementation. This is lower than that recorded in a Swedish euthyroid population half a century ago having had low-grade table-salt iodine supplementation for 20 years. Values for hyperthyroid patients, however, do not appear to have been affected likewise.

Morbidity, mortality, and quality of life for patients treated with levothyroxine.

In a population study of 1462 middle-aged women initiated in 1968 and 1969 we identified 29 women treated with levothyroxine from 1 to 28 years. In a 12-year follow-up in 1980 and 1981 we investigated the subjects for end-point myocardial infarction, diabetes mellitus, stroke, cancer, and death (the status of 99.7% of the initial participants was established). The women treated with levothyroxine showed no increase in morbidity or mortality. Of the 24 women still receiving levothyroxine in 1980 and 1981, 22 had serum thyrotropin and triiodothyronine concentrations with-in reference limits. These individuals were compared with the 968 women from the population study having no history of thyroid disease, and appeared identical as to laboratory and clinical data, with the exception of a slightly higher body mass, taller stature, and lower serum cholesterol concentration. The treated group did not differ in a life quality estimate based on 19 questions regarding life satisfaction and sensory function. We conclude that the levothyroxine-treated woman suffers no side effects from her life-long therapy.

Body weight and body composition changes after treatment of hyperthyroidism.

Body composition changes in nine adults with hyperthyroidism were determined with dual energy x-ray absorptiometry and computed tomography at diagnosis and after 3 and 12 months of euthyroidism achieved by surgery, antithyroid drugs, or treatment with radioiodine. Mean body weight was 67.6 kg at diagnosis and increased 2.7 kg (P=0.06) and 8.7 kg (P < 0.001) after 3 and 12 months of euthyroidism, respectively. Basal metabolic rate decreased from 2087 Cal/24 h at diagnosis to 1601 Cal/24 h at 12 months (P=0.001), whereas reported energy intake dropped from 3244 to 2436 Cal/24 h (P=0.01). According to dual energy x-ray absorptiometry, body fat was unchanged at 3 months, but increased by 5.3 kg (P < 0.0001) at 12 months. Fat-free mass increased 2.7 kg (P=0.003) at 3 months and 3.5 kg (P < 0.0001) at 12 months. Changes in bone mineral content and density did not reach significance. According to computed tomography, skeletal muscle plus skin areas increased by 11% (trunk) and 18% (thigh) at 3 months and by 17% (trunk) and 25% (thigh) at 12 months. There was no increase in sc adipose tissue (AT) at 3 months, but at 12 months this AT depot increased by 15% (thigh) and 33% (trunk). Intraperitoneal AT showed a borderline significant increase by 28% (P=0.08) at 3 months and by 40% (P=0.015) at 12 months. Areas of visceral organs and bone tissue of femur did not change significantly during the study. It is concluded that during early recovery from hyperthyroidism, priority is given to the replenishment of skeletal muscles and ip AT, whereas sc AT is increased at a later stage.

Debilitating chronic pain syndromes after presumed intraneural injections.

This report presents seven patients with severe disability established at the time of a peripheral nerve block. In most of the cases, the injection was administered as a routine procedure by an experienced anesthesiologist. The patient histories suggest that the condition, which can be resistant to all treatment, in most cases could have been avoided if careful attention had been given to the occurrence of pain during the nerve block. It is likely that the risk of devastating iatrogenic disability can be minimized if a few basic principles are respected during the administration of peripheral nerve blocks.

Radioiodine treatment of hyperthyroidism in a pregnant women.

UNLABELLED: We describe the effects of radioiodine treatment of a pregnant thyrotoxic woman. METHODS: The woman received 500 MBq of (131)I in her 20th gestational week. The pregnancy was discovered 10 days after radioiodine administration. A gamma camera examination of the abdomen at that time showed a distinct focus of activity, which was interpreted as the fetal thyroid. Gamma camera examinations of the mother and fetus were performed at 10, 11, 12, 13 and 18 days after administration of the therapeutic activity and were the basis of dose calculations. The child was examined by hormone tests and mental performance tests, up to 8 yr after birth. RESULTS: The uptake at 24 hr postadministration was calculated to be 10 MBq (2%) in the fetal thyroid gland. The effective half-life was 2.5 days, giving a calculated absorbed dose to the fetal thyroid gland of 600 Gy, which is considered to be an ablative dose. The calculated absorbed dose to the fetal body, including brain, was about 100 mGy, and 40 mGy to the fetal gonads. Doses were estimated taking contributions from radioiodine in the mother, the fetal body and the fetal thyroid into consideration. The woman was encouraged to continue her pregnancy and received levothyroxine in a dose to render her slightly thyrotoxic. At full term, an apparently healthy boy, having markedly raised cord blood serum thyroid-stimulating hormone concentration and subnormal thyroxine (T4) and low-normal triiodothyronine (T3) concentrations, was born. Treatment with thyroxine was initiated from the age of 14 days, when the somatosensoric evoked potential latency time increased to a pathological value and hormonal laboratory tests repeatedly confirmed the hypothyroid state. At 8 yr of age, the child attends regular school. A neuropsychological pediatric examination showed that the mental performance was within normal limits, but with an uneven profile. He has a low attention score and displays evidently subnormal capacity regarding figurative memory. CONCLUSION: Radioiodine treatment in pregnancy in the 20th gestational week does not give a total absorbed dose to the fetal body that justifies termination of pregnancy. A high absorbed dose to the fetal thyroid, however, should be the basis of the management of the pregnancy and offspring.

Inhibitory effect of piracetam on platelet-rich thrombus formation in an animal model.

Intravenous administration of piracetam to hamsters reduced the formation of a platelet-rich venous thrombus induced by a standardised crush injury, in a dose-dependent fashion with an IC50 of 68 +/- 8 mg/kg. 200 mg/kg piracetam also significantly reduced in vivo thrombus formation in rats. However, in vitro aggregation of rat platelets was only inhibited with piracetam-concentrations at least 10-fold higher than plasma concentrations (6.2 +/- 1.1 mM) obtained in the treated animals. No effects were seen on clotting tests. In vitro human platelet aggregation, induced by a variety of agonists, was inhibited by piracetam, with IC50's of 25-60 mM. The broad inhibition spectrum could be explained by the capacity of piracetam to prevent fibrinogen binding to activated human platelets. Ex vivo aggregations and bleeding times were only minimally affected after administration of 400 mg/kg piracetam i.v. to healthy male volunteers, resulting in peak plasma levels of 5.8 +/- 0.3 mM. A possible antiplatelet effect of piracetam could be due to the documented beneficial effect on red blood cell deformability leading to a putative reduction of ADP release by damaged erythrocytes. However similarly high concentrations were needed to prevent stirring-induced "spontaneous" platelet aggregation in human whole blood. It is concluded that the observed antithrombotic action of piracetam cannot satisfactorily be explained by an isolated direct effect on platelets. An additional influence of piracetam on the rheology of the circulating blood and/or on the vessel wall itself must therefore be taken into consideration.

The pain intensity at analgesic intake, and the efficacy of diflunisal in single doses and effervescent acetaminophen in single and repeated doses.

A double-blind, randomized analgesic trial was carried out in 150 patients undergoing surgical removal of their 2 impacted lower wisdom teeth. The analgesic efficacy of effervescent acetaminophen 500 or 1000 mg in a 2-dose regimen was compared with that of diflunisal 500 mg in a single dose. Each dose was taken when subjectively needed and the pain intensity was measured on a visual analog scale during the 10-hour period after first medication. The best pain reduction was achieved with diflunisal. The difference between diflunisal 500 mg and acetaminophen 1000 mg was significant, as was that between acetaminophen 1000 and 500 mg. The peak effect after the first dose occurred later but was greater with diflunisal than with acetaminophen. Patients needing analgesics at low pain intensities seemed to discriminate better between treatments, and the efficacy of acetaminophen was weakly dependent on the initial pain intensity. This intensity was difficult to predict, and only a poor correlation was found between the initial pain intensity and the patient's prior estimate of this.

A monoclonal antibody identifies 2134P fimbriae as adhesins on enterotoxigenic Escherichia coli isolated from postweaning pigs.

Fimbriae (pili) of enterotoxigenic Escherichia coli (ETEC), including K88, K99, 987P, and F41, are adhesins that facilitate intestinal colonization in neonatal pigs. K88 is also associated with some ETEC isolated from weaned pigs. Many ETEC isolates from weaned pigs do not express known adhesins and are termed 4P-. A novel bacterial adhesin, 2134P, was recently identified on two 4P- ETEC isolates from weaned pigs. In this study, we identified a 2134P-specific monoclonal antibody, mAb 6C7/C1, that blocked the binding of 2134P+ bacteria to intestinal epithelial cells. Indirect immunofluorescent antibody and immunoperoxidase assays using mAb 6C7/C1 confirmed that the 2134P adhesin is expressed in vivo by adherent bacteria in pigs challenge-exposed with 2134P+ ETEC. 2134P was detected on 31% of 189 postweaning diarrhea 4P- ETEC isolates from the National Animal Disease Center's culture collection by dot blot immunoperoxidase assays using mAb 6C7/C1. We conclude that 2134P is a bacterial adhesin and is an important virulence attribute of some ETEC that cause diarrhea in weaned pigs.

Combined spinal and epidural anesthesia for labor and cesarean delivery in a patient with Guillain-Barre syndrome.

BACKGROUND AND OBJECTIVES: The anesthetic management of labor, delivery, and cesarean delivery in patients with active or resolving Guillain-Barre syndrome is not well defined. Using a combined spinal and epidural (CSE) technique in such a rare clinical situation has not been previously reported. CASE REPORT: A 32-year-old woman gravida 2, para 0 was diagnosed with Guillain-Barre syndrome at 21 weeks of pregnancy. Paralysis spread up to the T4 level. Three months later, she was admitted for labor at term. She presented in severe labor pain and it was decided to proceed with CSE analgesia. No unusual hemodynamic instability, signs of autonomic dysfunction, or increased sensitivity to local anesthetics was noted. After several hours, delivery by cesarean section was required and epidural anesthesia was then used. The patient had an uncomplicated postpartum course. CONCLUSION: Careful evaluation and documentation of the patient's baseline neurological status, a thorough discussion with the patient regarding the risks and benefits of the technique for labor analgesia, and an appreciation of the limited experience with this kind of clinical situation are important.

Combined use of bone grafts and Brånemark fixtures in the treatment of severely resorbed maxillae.

Bone grafts from the hip in combination with Brånemark self-tapping fixtures have been used to rehabilitate patients with extremely resorbed maxillae. Experiences and results from the first ten consecutive cases have been analyzed to form the basis for further use of the method. Eight of 57 fixtures placed have been lost to date. Surgical complications, including exposure of the bone transplant, have occurred in three patients. The method should be used with caution, and cases should be meticulously chosen to exclude those who do not have proper motivation to endure the long-lasting and demanding surgical and prosthetic procedures required. The combined use of implants and transplants should not be used routinely until a long-term evaluation of the method and results has been made.

Treatment of the severely resorbed maxillae with bone graft and titanium implants: histologic review of autopsy specimens.

One of a series of patients with extremely resorbed maxillae treated with bone grafts from the hip in combination with Brånemark self-tapping fixtures died in a car accident 4 months after implant surgery. Autopsy specimens from this patient were analyzed to evaluate the amount and extent of "osseointegration" after 4 months of healing. Histologic examination revealed that minimal bone was in direct contact with the titanium and the general pattern was that of soft tissue screw anchorage. There were no signs of sequestering of the transplanted bone. The connection between the nasal cavity and the sinus mucosa with respect to the transplants seemed to be without adverse reactions. The superior part of the transplant did show signs of newly formed bone. The grafted specimens showed indications of delayed bone response compared to the nongrafted situation. All implants were clinically stable as studied postmortem.

Bone grafts and Brånemark implants in the treatment of the severely resorbed maxilla: a 2-year longitudinal study.

A combination of horseshoe-shaped iliac bone grafts and Brånemark implants was used in 30 patients with severely resorbed maxillary alveolar ridges. All patients were followed clinically for 2 years and evaluated with regard to prosthesis stability, fixture survival, wound healing complications, and soft tissue conditions. Surgery was performed by the same oral surgeons using identical procedures, and the prosthetic treatment was performed by the same prosthodontist. The development group included the first 10 patients and the routine group included the following 20. Fixture survival in the development group was 54.4%, whereas 88.3% of the fixtures in the routine group have survived after 2 years. The average fixture survival in the study was 77.4%. Three patients in the development group lost all fixtures, primarily the result of trauma to the grafted region. With respect to the difficult situation many of these patients experienced, the survival rate should be considered most acceptable.

Extraoral or intraoral approach in the oblique sliding osteotomy of the mandibular rami? Clinical experience and results.

The clinical results of oblique sliding (subcondylar) osteotomy of the mandibular rami performed by the extraoral or intraoral approach were compared. The patient material comprised 40 patients with mandibular prognathism. Twenty patients were operated upon using the extraoral approach and 20 patients were operated on using the intraoral approach. All patients had intermaxillary fixation for 7 weeks. The patients in both groups were followed up for 18 months. The experience of the operations was that the intraoral approach gave a shorter operation time than the extraoral approach. The extraoral approach, however, gave better visibility in the operation field and greater possibilities of manipulating the proximal fragment into an optimal position. In the follow-up evaluation, there were no significant differences between the two surgical techniques with regard to dental relapse, post-operative occlusion and mandibular function.

Intraoperative thrombolytic treatment of microarterial occlusion by selective rt-PA infusion.

The development of microvascular thrombosis during replantation surgery or free-flap transfer is generally best treated by identification of the problem, vascular revision, and reanastomosis. It is not unique, however, that surgical measures alone are insufficient or undesirable. Pharmacologic adjuncts are widely used for the prevention and sometimes treatment of microvascular thrombosis in surgical practice, but the benefit of thrombolytic agents, effective in dissolving an already established thrombus, is usually considered counterlevered by the fear of uncontrollable bleeding. However, selective infusion of the drug reduces the risk for systemic complications considerably and may therefore be considered in peripheral microvascular reconstruction. The technique was used successfully in a case of digital revascularization, where an arterial thrombosis was dissolved with the use of recombinant tissue plasminogen activator (rt-PA).