Therapy Bypass Research Articles

Diagnosis of Chronic Pancreatitis and Newer Aspects of Pain Control

The diagnosis of chronic pancreatitis in the UK largely rests on the combination of the clinical presentation which usually features pain which is often provoked by food and/or alcohol. There is usually a 30 to 40-min delay between the stimulus and the pain and, after exclusion of other causes of pain, an ERCP is performed. A minority of patients will have pancreatic function tests carried out while increasingly the diagnosis is being made by MR scanning. The control of pain is often the most important aspect of management to the patient. In those with large ducts due to compression of focal areas of the duct system surgical by-pass therapy is indicated. There is a bigger problem in patients with small ducts and chronic pancreatitis in whom extensive resection may be inappropriate. Our experience with minimally invasive thoracoscopic splanchnicectomy has been encouraging over the last three years. Having previously tried both percutaneous coeliac ganglion block and surgical excision of this nerve tissue, it is a great deal easier to carry out this procedure which ususally takes only 15–20 min per side. Patients are usually only admitted for 48 h and the immediate beneficial effect usually results in opiate analgesia being discontinued with considerable improvement in the quality of life. While there is a slight drop-off in benefit between 6 and 12 months post-operatively, the clinical effectiveness of this approach is to be commended and the author’s experience will be presented to support this view.

Factor VIII inhibitors in mild and moderate-severity haemophilia A.

Inhibitors are an uncommon complication of mild haemophilia, occurring in 3-13% of patients and usually arising during adulthood. The risk of inhibitor development in this group appears to be associated with relatively few high-risk factor VIII genotypes clustered in the A2 and C2 domains, especially the Arg593-Cys and the Trp2229-Cys mutations. Kindreds with these mutations have an inhibitor incidence of up to 40%. These mutations may induce a stable conformational change in the factor VIII molecule rendering it antigenically distinct from wild-type factor VIII. Inhibitors in mild haemophilia usually cross-react with endogenous factor VIII reducing the basal VIIIC to < 0.01 IU/ml, and causing spontaneous bleeding. This bleeding is sometimes severe and life-threatening, two-thirds of patients developing a pattern of soft tissue, gastrointestinal (GI) and urinogenital bleeding reminiscent of acquired haemophilia. Bleeding has been treated with human and porcine factor VIII, bypass therapy and DDAVP. Recombinant factor VIIa and DDAVP have the advantage that they do not induce an anamnestic rise in inhibitor titre. About 60% of these inhibitors disappear in the remainder over a median of 9 months. Few of these inhibitors recur, suggesting that most such patients have become tolerant. The inhibitors persist long-term and remain troublesome in about 40% of patients. The limited data available on immune tolerance induction in this group indicate a generally poor response to this approach. Two of nine achieved tolerance, with a partial response in a further four. Inhibitors are an uncommon but life-threatening complication of haemophilia. This complication should be considered when selecting the treatment modality for patients with a family history of inhibitors, and DDAVP used whenever possible.

Meeting highlights Part II: 70th Scientific Sessions of the American Heart Association.

Gene therapy seems to be moving past the “proof of principle” phase with two new treatments described at the 70th Scientific Sessions of the American Heart Association meeting held in Orlando, Fla November 9 through November 12, 1997. “It is an opening door,” said Valentin Fuster, MD, incoming American Heart Association President and director of the Cardiovascular Institute at Mount Sinai Medical Center in New York City. “It’s not definitive, but it’s certainly very exciting.” In each case, researchers used genes to tinker with or get around disease-causing problems rather than striking directly at the cause of the disorder itself. These kinds of “incremental” gene therapies will probably become more common in the next few years as the field itself matures. The two groups took very separate attacks on the problem of occlusion in limbs, or limb ischemia, which affects between 100 000 and 200 000 people in the United States each year. One was an in vivo experiment injecting genes directly into muscles to encourage the growth of collateral blood vessels. The second was ex vivo and involved bathing a vein graft in a solution containing an oligodeoxynucleotide (ODN) that is a transcription factor decoy to block gene activity. Clinical researchers at St. Elizabeth’s Medical Center in Boston, Mass, attempted to stimulate the growth of collateral blood vessels in the patients’ legs that had been occluded by atherosclerotic lesions. In a technique that Jeffrey Isner, MD, of St. Elizabeth’s and Tufts Medical School called “therapeutic angiogenesis,” the researchers inserted the gene for vascular endothelial growth factor (VEGF) directly into the muscles of the patients’ legs. His hope was that VEGF would encourage the growth of blood vessels that would provide flow to the ischemic areas of the leg. Patients could not be candidates for bypass therapy or other types …

Extracorporeal membrane oxygenation causing asymmetric vasculopathy in neonatal infants

Background: Extracorporeal membrane oxygenation (ECMO) is a form of cardiopulmonary bypass therapy used in term or near-term infants with severe cardiorespiratory disorders not responsive to conventional intensive care interventions. An ECMO-associated retinal vasculopathy has been described with little reference to the specific condition of the patient. We examined the eyes of 91 infants who underwent ECMO treatment. An assessment was made of the following: (1) when retinal changes occurred, (2) whether there was a particular systemic disorder or ECMO approach associated with these retinal findings, and (3) whether there may be ocular sequelae from this development. Methods: Ninety-one neonates were treated with ECMO for meconium aspiration syndrome (MAS), primary persistent pulmonary hypertension of the newborn, sepsis, congenital diaphragmatic hernia (CDH), respiratory distress syndrome (RDS), and blood aspiration. Venoarterial bypass was performed in 73 patients. The remaining 18 patients underwent venovenous bypass. Ophthalmologic examinations were performed during bypass in 6 infants and within 3 weeks of ECMO in the remainder. Results: Asymmetric retinopathy (left eye > right eye) was discovered in six infants with CDH and in one infant with RDS within a 2-week period after bypass, demonstrating venous tortuosity with or without intraretinal hemorrhages. One infant treated for MAS had a left eye intraretinal hemorrhage only. All patients with the noted retinal changes underwent venoarterial cannulation. Six of 9 patients with CDH had retinal findings noted compared with 1 of 10 patients with RDS and 1 of 35 patients with MAS. Conclusion: Because we were able to examine infants while they were receiving ECMO or shortly after termination of bypass, asymmetric vasculopathy was found in a greater percentage of our patients compared with a similar large case series. ECMO-associated retinal vasculopathy appeared to disproportionately occur in those patients with CDH who underwent venoarterial bypass. Further study of retinal vascular changes in patients with CDH should be performed to assess long-term effects.

Erste Ergebnisse der perkutanen Therapie von Poplitealaneurysmen mit Stents

Are percutaneous stents a therapeutic alternative to bypass surgery in the treatment of popliteal aneurysms? Three patients with femoropopliteal occlusion related to popliteal aneurysms were treated percutaneously. In two cases coated stents were used. In the third patient who underwent prior bypass surgery due to local fibrinolysis a reperfusion of the aneurysm occurred. He was treated with a Wallstent. Primary stent treatment was successful in all cases. There were no complications. One patient was lost to follow-up. One of the two coated stents occluded after one month due to a poor run-off of only one lower limb artery. The other coated stent is still patent after 6 months proven by angiography. Percutaneous therapy with coated stents could be an alternative to surgical bypass therapy for popliteal aneurysms. Obviously long-time patency is related to sufficient run-off.

Procoagulant Activity of Reversibly Acylated Human Factor Xa

The plasma clotting factors used to treat hemophiliacs who have developed inhibitory antibodies have a shared history of limited clinical safety and utility. To improve on existing bypass factors, we have developed a reversibly acylated form of human plasma factor Xa capable of providing a time-dependent release of procoagulant activity. Factor Xa was treated with p-amidinophenyl p'-anisate to generate anisoyl Xa. The chemical modification of the protein involves acylation of the active site serine residue of factor Xa. Anisoyl Xa deacylated in a time, pH, and temperature-dependent manner. Active factor Xa generated on deacylation of anisoyl Xa exhibited amidolytic and prothrombinase complex activities in in vitro assays, the level being comparable to those of untreated factor Xa. When Anisoyl Xa was infused into rabbits, active factor Xa was generated on deacylation of the acylated enzyme, which shortened the activated partial thromboplastin time (APTT) in a dose-dependent manner. The duration of effect on rabbit APTT could be directly correlated to the level of human plasma factor Xa. Because anisoyl Xa bypasses the "tenase" complex that is compromised in hemophilia A and B and is unaffected by inhibitory antibodies, it has the potential to be used as an effective bypass therapy.

Continued pulmonary recovery observed after discontinuing extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) is a valuable therapy for the treatment of reversible lung disease in neonates. Associated with this treatment, however, are risks for complications that increase with the duration of therapy. We evaluated alveolar-arterial oxygen tension difference P(A-a)O2 pulmonary compliance (CL), and functional residual capacity (FRC) in 20 infants immediately after ECMO was discontinued, and again 24 hours thereafter. We measured CL by pneumotachography and esophageal manometry and FRC by helium dilution. Mean (+/- SEM) values for CL and FRC increased (CL from 0.28 +/- 0.02 to 0.35 +/- 0.03 mL/cmH2O)/kg and FRC from 18.6 +/- 1.4 to 22.2 +/- 1.1 mL/kg; P < 0.05), and P(A-a)O2 and the oxygenation index (OI) decreased (200 +/- 19 to 169 +/- 14 mm Hg and 6.9 +/- 0.44 to 5.4 +/- 0.5, respectively; P < 0.02), over the 24 hour period following ECMO. Nineteen of 20 infants experienced improvement in at least two of these parameters. Improvements were found to be greatest in the infant with the worst lung function immediately after discontinuing ECMO, and in the ten infants who had not received pancuronium bromide for inducing skeletal muscle paralysis, following decannulation from ECMO. These data indicate that improvement in lung function following ECMO will generally continue over the 24 hour period following the termination of cardiopulmonary bypass, and that borderline pulmonary status may not preclude discontinuation of bypass therapy.

Disabling cerebral transient ischemic attacks

The surgical management of an emerging clinical entity, namely disabling transient cerebral ischemic attacks, is described. A series of 19 patients treated in a 2-year period (12 with anterior circulation dysfunction and seven with posterior insufficiency) met the following criteria: 1) stereotypical recurrent episodes of transient neurological dysfunction related to the anterior or posterior circulation distribution; 2) failure of maximum medical therapy to control the transient neurological dysfunction; 3) four-vessel cerebral angiography demonstrating an isolated vascular territory corresponding to patient symptoms; 4) inhalation xenon cerebral blood flow studies with at least three of eight probe-pairs showing significant asymmetries in the initial slope index, localizing an area of relative oligemia to the symptomatic hemisphere (anterior circulation only); and 5) severe restriction of lifestyle due to transient ischemic attacks (TIA's). Seventeen patients underwent surgical bypass therapy: deep sylvian superficial temporal artery (STA)-middle cerebral artery (MCA) bypass in nine; surface STA-MCA bypass in three; STA-superior cerebellar artery bypass in three; STA-posterior cerebral artery bypass in one; and aorta-carotid artery bypass in one. There was one perioperative death and four perioperative strokes (two ipsilateral and two contralateral to the operated side). The average follow-up period was 14 months. Of the 16 surviving surgically treated patients, 13 (81%) have had an excellent to good outcome with complete resolution of TIA's and minimal neurological deficits. Three patients had a poor outcome with either a significant persistent neurological deficit or continued TIA's. The two patients not treated surgically continue to have vertebrobasilar insufficiency episodes while receiving oral anticoagulation medication. The overall mortality rate (5.5%) and stroke morbidity rate (22.2%) of surgical therapy for disabling TIA's are high in this neurologically unstable group of patients, but are associated with an 81% excellent to good response. Although the natural history of disabling TIA's is not known, these patients present with significant to total disability due to their symptoms. It is concluded that disabling TIA's respond to surgical revascularization and may represent an indication for cerebral revascularization surgery.

Electroencephalographic Studies in Neonates during Extracorporeal Membrane Oxygenation

ABSTRACT.Extracorporeal membrane oxygenation (ECMO) is a modified form of heart/lung bypass therapy utilized in the full-term infant with life-threatening respiratory failure. The risks of ECMO, including intracranial hemorrhages and their subsequent effects, make it important to check the condition of brain function before, during, and after ECMO therapy. Therefore, serial EEG recordings are necessary for these patients. Knowledge of EEG recording techniques in this population as well as neonatal respiratory physiology is a requirement for the neurodiagnostic technologist faced with recording EEGs from these infants.

Arteriography of Coronary Disease at Clinical Onset

The coronary arteriographic anatomic findings in 491 male patients clinically symptomatic for less than six months are described. Single and multiple vessel disease was noted, respectively, in 40 and 60 percent with 6.5 percent also manifesting left main coronary disease. Our findings indicate that severe coronary artery disease is present early in the symptomatic phase and that patients presenting with initial inferior myocardial infarctions may represent a select group having an excessive frequency of severe coronary disease suitable for early angiographic detection and surgical bypass therapy.

Coronary arterial spasm in Prinzmetal angina. Documentation by coronary arteriography.

A woman with Prinzmetal angina displayed spontaneous attacks of myocardial ischemia characterized by severe chest pain, hypotension, inferior-wall ST-segment elevation and transient complete heart block. Coronary arteriography during several fully developed spontaneously occurring attacks demonstrated spasm of a right coronary artery that appeared to be anatomically normal. The site, extent and degree of obstruction varied during individual attacks. Immediately after an attack subsided the coronary artery appeared normal. These observations suggest that coronary arteriography should be attempted, if possible, during clinical attacks of pain in patients with Prinzmetal angina. Even those who have a focal atherosclerotic obstruction may have additional distal coronary arterial spasm. Spasm beyond a proximal obstruction may preclude the use of saphenous-vein bypass therapy alone. Coronary arterial vasodilators may be an important additional therapeutic measure.