Plasmodium vivax Duffy binding protein: baseline antibody responses and parasite polymorphisms in a well-consolidated settlement of the Amazon Region.

OBJECTIVE: To investigate risk factors associated with the acquisition of antibodies against Plasmodium vivax Duffy binding protein (PvDBP) - a leading malaria vaccine candidate - in a well-consolidated agricultural settlement of the Brazilian Amazon Region and to determine the sequence diversity of the PvDBP ligand domain (DBP(II)) within the local malaria parasite population. METHODS: Demographic, epidemiological and clinical data were collected from 541 volunteers using a structured questionnaire. Malaria parasites were detected by conventional microscopy and PCR, and blood collection was used for antibody assays and molecular characterisation of DBP(II). RESULTS: The frequency of malaria infection was 7% (6% for P. vivax and 1% for P. falciparum), with malaria cases clustered near mosquito breeding sites. Nearly 50% of settlers had anti-PvDBP IgG antibodies, as detected by enzyme-linked immunosorbent assay (ELISA) with subject's age being the only strong predictor of seropositivity to PvDBP. Unexpectedly, low levels of DBP(II) diversity were found within the local malaria parasites, suggesting the existence of low gene flow between P. vivax populations, probably due to the relative isolation of the studied settlement. CONCLUSION: The recognition of PvDBP by a significant proportion of the community, associated with low levels of DBP(II) diversity among local P. vivax, reinforces the variety of malaria transmission patterns in communities from frontier settlements. Such studies should provide baseline information for antimalarial vaccines now in development.

Location of ubiquinone-10 (CoQ-10) in phospholipid vesicles.

Egg yolk phosphatidylcholine (PC) liposomes were prepared by ultrasonic irradiation. At least 25 mol% of coenzyme Q-10 (CoQ-10) can be incorporated nonstoichiometrically into PC liposomes. Electron microscopy showed no visible influence of CoQ-10 on the membrane structure. Nuclear magnetic resonance spectra of sonicated PC liposomes containing CoQ-10 showed two peaks (3.82 and 3.98 ppm) due to CoQ-10 methoxyl protons and a 'high-field component' (1.52 and 1.58 ppm). The areas of these peaks were inversely related and influenced by the time of ultrasonic irradiation. After short sonication the low-field positions (3.98/1.58 ppm) are favoured, after long sonication the high-field positions (3.82/1.52 ppm). No gradual shift of the two peaks is observed. The 'critical' liposome diameter was found to be between 500 to 700 A. Lanthanide induced pseudocontact shift on CoQ-10 resonances ('high-field component' and methoxyl) does not lead to a split of the peaks and the difference between them remains constant. It is concluded that CoQ-10 is incorporated into the membrane core, beyond C-2 of the PC acyl chains, with two bilayer curvature-dependent resonance positions.

Role of the carboxyl-terminal region, di-leucine motif and cysteine residues in signalling and internalization of vasopressin V1a receptor.

The structural requirements for internalization and signalling of the vasopressin V1a receptor were investigated in stably transfected HEK-293 cells. Removal of the 51 C-terminal amino acids did not affect vasopressin binding, calcium signalling, heterologous desensitization or internalization of the receptor. Deletion of 14 additional amino acids reduced vasopressin-dependent calcium increase and impaired receptor internalization. Substitution of cysteines 371-372 did not affect intracellular signalling, but decreased endocytosis by 26%. Substitution of the 361-362 leucine by alanine residues reduced by 56% V1a receptor sequestration without affecting calcium signalling. These results indicate that di-cysteine and mostly di-leucine motifs present in the C-terminal region of the V1a receptor are involved in its internalization.

Evolution of regional ischemia distal to a proximal coronary stenosis: self-propagation of ischemia.

The temporal evolution of myocardial ischemia was studied in open chest dogs at constant preload, afterload and heart rate. In one group of animals, a variable circumflex arterial stenosis was used to maintain constant distal circumflex arterial hypotension (40 to 50 mm Hg). During a 3 hour period of stenosis, flow in the subendocardial fourth of the ischemic ventricular wall decreased from 0.22 to 0.09 ml/g per min (P less than 0.02), whereas subepicardial flow was not significantly changed. Local vascular resistance, therefore, doubled in the most ischemic area of myocardium. In a second group of animals in which proximal coronary stenosis was held constant and pressure varied, an ischemia-mediated increase in local vascular resistance was also demonstrated. In addition, a reciprocal relation was observed between changes in flow in the left anterior descending coronary region and changes in collateral flow to the region of the circumflex artery. A coronary steal mechanism and an ischemia-mediated resistance increase may be two means by which ischemia is self-propagating.

Significance of subendocardial S-T segment elevation caused by coronary stenosis in the dog. Epicardial S-T segment depression, local ischemia and subsequent necrosis.

A model of partial thickness ischemia has been developed using subendocardial S-T elevation without epicardial S-T elevation to detect partial thickness ischemia which is sufficient to cause subsequent necrosis. Subendocardial blood flow in this model (measured with radioactive microsphere techniques) may be reduced to 25 percent of normal (P less than 0.001) by coronary stenosis and tachycardia while subepicardial flow remains normal. Epicardial S-T depression seems to indicate reciprocally subendocardial S-T elevation as long as a layer of nonischemic epicardial muscle is present, but when ischemia becomes transmural, epicardial S-T elevation occurs. Regional pressure-flow relations were determined as distal coronary pressure was reduced at a constant aortic pressure, heart rate and cardiac output. These relations revealed remarkably effective autoregulation of epicardial blood flow concomitant with progressive subendocardial ischemia.

Interhospital transport of patients with ongoing intraaortic balloon pumping.

During a 5-year period (1979 to 1983), 50 consecutive patients undergoing continuous intraaortic balloon (IAB) pumping were transferred from Evanston Hospital to Northwestern Memorial Hospital (16 miles), where they underwent cardiac operation. All patients had cardiac catheterization before transfer. Indications for IAB were cardiogenic shock (9 patients), postinfarction angina (18 patients), unstable angina (9 patients), evolving myocardial infarction (3 patients), accelerating angina or hemodynamic instability during cardiac catheterization (9 patients) and prophylactic insertion for high-grade left main stenosis (2 patients). Transportation after stabilization was uneventful in all patients. All patients underwent operative coronary revascularization. There was concomitant mitral valve replacement in 3 patients, acute ventricular septal defect repair in 1 patient, aortic valve replacement in 1, and ventricular aneurysmectomy in 1. Three patients (5%) died postoperatively. Nine patients (20%) had complications directly related to IAB insertion. One patient required femoral-femoral arterial bypass preoperatively, 4 patients had postoperative lower limb ischemia treated by IAB removal or thrombectomy and 1 patient had thrombocytopenia (less than 60,000/mm3), 1 false aneurysm, 1 anterior compartment syndrome and 1 prolonged bleeding at the insertion site. Interhospital transfer with IAB pumping in progress should not be restricted to patients with cardiogenic shock, but can be effectively used for all patients who require preoperative IAB insertion.(ABSTRACT TRUNCATED AT 250 WORDS)

Endocardial activation mapping and endocardial pace-mapping using a balloon apparatus.

The relation between endocardial activation mapping and endocardial pace-mapping was evaluated in 8 dogs while they were on cardiopulmonary bypass. Pacing or recording was accomplished by using a balloon apparatus (with 32 bipolar electrodes) inserted through a left apical ventriculotomy. Ventricular tachycardia (VT) was produced by occlusion followed by reperfusion of the left anterior descending coronary artery. During each VT, activation mapping was performed and early sites determined. Pace-map correlates (sites at which endocardial pacing produced a similar QRS morphology to that of the VT) were also determined. Isochronous maps were constructed for activation mapping and pace-mapping. There was a total of 29 morphologically distinct VTs. Groups were delineated according to correlations between activation mapping and pace-mapping. In 14 episodes of VT (group 1), pace-mapping confirmed the findings of activation mapping with all early sites being pace-map correlates (total number of early sites (tES) = 19; total number of pace-map correlates (tPMC) = 88; tES same as tPMC = 19). In 9 episodes of VT (group 2), there was a partial correlation between pace-mapping and activation mapping, such that pace-mapping when used with activation mapping appeared to further delineate the region of arrhythmogenesis (tES = 31; tPMC = 59; tES same as tPMC = 14). In 6 episodes of VT (group 3), there was no correlation between pace-mapping and activation mapping (tES = 15; tPMC = 0). With the balloon apparatus, endocardial activation mapping can be performed without the need for sustained monomorphic VT, and endocardial pace-maps may be generated easily.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental coronary artery fistula.

Despite numerous clinical reports of coronary artery fistulas, there have been no laboratory models. A circumflex coronary-pulmonary artery fistula was constructed with a vein graft in 11 adult foxhounds. A temporary intravascular shunt obviated the need for cardiopulmonary bypass. Measurements of aortic flow, arterial pressure, left ventricular pressure and its derivative, heart rate, and flow in the proximal coronary, distal coronary, and fistula were made with the fistula open and closed in 9 animals. Mean fistula flow was 89 c.c. per minute, representing a 1.1:1 left-to-right shunt. Mean proximal coronary flow increased 211 per cent, and there was a relative steal of 26 per cent of distal coronary flow with the fistula functioning. Phasic flow patterns showed continuous systolic and diastolic flow in the proximal coronary artery and fistula. Despite the striking changes in coronary flow patterns, there was no significant effect on measured left ventricular function. Futher uses for this model and variations of it aresuggested.

Metastatic squamous cell carcinoma to the heart. Unusual cause of angina decubitus and cardiac murmur.

A 61-year-old woman was admitted to the hospital with the new onset of angina at rest and an ECG consistent with anterior wall ischemia. She was also noted to have a new cardiac murmur. Eighteen months earlier, she had been treated for squamous cell carcinoma of the base of the tongue. Thirteen months ago, she had local recurrence treated with radiotherapy, but had no evidence of recurrent or metastatic disease at the time of present admission. Echocardiography revealed intracardiac and extracardiac masses; surgical biopsy confirmed metastatic carcinoma to the heart which was responsible for her symptoms and the new murmur. Symptomatic cardiac metastases from squamous cell carcinoma is an unusual situation which, in this case, was easily diagnosed with echocardiography.

Laser-assisted parenchyma-sparing pulmonary resection.

The neodymium:yttrium-aluminum-garnet laser is an excellent tool for removing lesions while sparing surrounding normal tissue. Local excision of 32 pulmonary lesions in 26 patients was performed with the Nd:YAG laser. Fourteen patients had moderate to severe impairment of pulmonary function: average forced vital capacity = 2.2 +/- 0.3 L and forced expiratory volume in 1 second = 1.3 +/- 0.3 L. Limited thoracotomy was used in the last 23 patients. The resected lesions included 16 primary malignant tumors: nine adenocarcinomas, five squamous carcinomas, and two large cell carcinomas. Eight of these lesions were classified as T1 N0, seven were T2 N0; and one was T1 N2. There were 10 metastatic lesions: three lymphomas, two adenocarcinomas, two leiomyosarcomas, and one case each of melanoma, squamous cell carcinoma, and renal cell carcinoma. There were six benign lesions: three granulomas, two hamartomas, and one carcinoid. Twelve lesions were deep seated, could not have been removed by wedge resection or segmentectomy, and would have necessitated lobectomy without this technique. With the laser, the lesion could be precisely excised with minimal loss of lung parenchyma. Mean operating time was 80 +/- 20 minutes; laser resection time was 15 +/- 8 minutes. Resection necessitated 10,000 to 20,000 J. Total blood loss was minimal (less than 100 ml). Chest tubes were always used and remained in place 5 +/- 2 days. The mean hospitalization time was 10 +/- 2 days. Pulmonary function testing, perform 6 weeks to 6 months after discharge, showed no significant difference from preoperative levels. To date, there have been no local recurrences (longest follow-up 2 years). The Nd:YAG laser is an excellent adjunct for pulmonary resection in patients who have marginal pulmonary function or who have deep parenchymal lesions not amenable to wedge resection. The operative technique for laser resection is presented.

Contribution of the bronchial circulation to lung preservation.

Short preservation time still severely limits lung transplantation. To determine the effect of bronchial arterial flush preservation, we studied 54 dogs using the isolated perfused working lung model. After baseline measurements, lungs were flushed with lactated Ringer's solution (60 ml/kg at 8 degrees C) by one of three methods: pulmonary artery perfusion, bronchial artery perfusion through a 15 cm closed aortic segment, or simultaneous pulmonary-bronchial artery perfusion. These groups were further subdivided and tested after 0, 4, and 17 hours of storage at 4 degrees C (n = 6 each). Lungs were ventilated (flow rate 140 ml/kg/min; inspired oxygen fraction 0.21) and continuously reperfused with normothermic deoxygenated autologous blood in a closed loop. Measured variables were hemodynamics, aerodynamics, and leukocytes in bronchoalveolar lavage. Survival time was determined from initial reperfusion to failure of the lung to oxygenate. After 0 and 4 hours of storage, there was no significant difference in survival times. After 17 hours, lungs subjected to pulmonary-bronchial artery perfusion survived longer than those perfused via either the pulmonary or bronchial arteries alone (120 +/- 24 versus 38 +/- 14 or 52 +/- 16 minutes; p less than 0.01). Pulmonary artery pressure and resistance in all groups except at failure were never different from baseline values in the intact animal. Shunts in the pulmonary-bronchial artery perfusion groups were closest to baseline at onset (8% +/- 4%) and remained lower throughout reperfusion than in the groups subjected to pulmonary or bronchial artery perfusion alone. After 17 hours, static compliance of pulmonary artery-perfused lungs was worse than baseline (1.1 +/- 0.2 x 10(-2) versus 3.2 +/- 0.7 x 10(-2) L/cm H2O/sec; p less than 0.05), whereas compliance in the pulmonary-bronchial artery perfusion groups remained constant (3.6 +/- 1.5 x 10(-2) L/cm H2O/sec). Elastic work performed by lungs subjected to pulmonary-bronchial artery flushing at onset was significantly lower when these lungs were reperfused immediately (201 +/- 14 versus 295 +/- 35 gm-m/min for pulmonary artery-flushed lungs) or after 4 hours of storage (229 +/- 30 versus 290 +/- 24 gm-m/min for pulmonary artery-flushed lungs). Bronchoalveolar lavage after 17 hours in the group subjected to pulmonary bronchial artery flushing demonstrated leukocyte counts similar to those of intact lungs (45 +/- 5 versus 29 +/- 8/mm3) and significantly less than in lungs subjected to pulmonary or bronchial artery flushing (137 +/- 18 or 82 +/- 10/mm3, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Delayed coronary artery dissection after angiography. A case description with successful operative treatment.

A patient is described in whom right coronary artery dissection occurred 48 hours after coronary angiography. Successful operative treatment consisted of immediate saphenous vein bypass grafting and ligation of the proximal coronary artery. Several aspects of the case are characteristic of this pathological entity as reported in the literature and suggest principles of surgical management.

Long-term morphologic and hemodynamic evaluation of the left ventricle after cardiopulmonary bypass. A comparison of normothermic anoxic arrest, coronary artery perfusion, and profound topical cardiac hypothermia.

In order to assess the long-term effects of cardiopulmonary bypass (CPB) in combination with pupular methods of myocardial protection, 37 dogs were placed on CPB for 100 minutes with the use of a bubble oxygenator without hemodilution. A separate group (I) of eight normal dogs served as a control for assessment of hemodynamic changes. The operative groups were as follows: II, continuous coronary perfusion with an empty, beating heart for 60 minutes at 35 degrees C.; III, hypothermic anoxic arrest (aortic occlusion) for 60 minutes with topical cold saline lavage (4 degrees C.); IV, anoxic arrest for 60 minutes at 35 degrees C. Subgroups of Groups III and IV received intracoronary perfusion with Ringer's lactate or Sacks' solution during aortic occlusion and were compared with those animals receiving no perfusion. Survival in Groups II and III was significantly better than in Group IV (82 and 92 per cent vs. 45 per cent). Coronary perfusion with Ringer's lactate or Sack's solution did not influence survival. The 23 survivors from all groups underwent left heart catheterization and LV cineangiography 5 months after operation. All three operative groups had significant elevation of LVEDP and depression of maximum developed dp/dt when compared with normal dogs. Ejection fraction was significantly depressed in Groups III and IV, and there was evidence of left ventricular hypokinesia and/or akinesia in all three operative groups. Differences in function between Groups II, III, and IV were not significant. The use of intracoronary solutions during anoxic arrest did not significantly influence these functional alterations. Evidence of subendocardial fibrosis was found in each of the operative groups, with the most marked changes found in the normothermic arrest group. Moderate fibrosis was present, however, in some survivors in both the continuous coronary perfusion and topical hypothermic arrest groups. These data indicate that although survival is greatly enhanced when coronary artery perfusion or topical hypothermia is used, neither method prevents chronic deterioration in ventricular function nor the development of subendocardial fibrosis.

Experimental air leaks in lung sealed by low-energy carbon dioxide laser irradiation.

When a focused carbon dioxide laser beam strikes a surface of tissue, the light energy is converted instantly into thermal energy, causing cells directly in the laser's path to vaporize. Because the carbon dioxide laser's energy is well absorbed by water, this thermal effect is attenuated at a distance of 100 mu. If the laser beam is "defocused," the same thermal energy is dissipated over a larger area, causing only desiccation and melting of tissue without vaporization; however, the depth of injury remains shallow. This modified technique has been used to seal artificially created air leaks in the canine lung. Twelve mongrel dogs were anesthetized, intubated, and ventilated. The lingula was exposed sterilely through a left thoracotomy. A 1 X 3-mm hole was made in the lung at 1 cm from the edge. The created air and blood leaks were sealed with a defocused carbon dioxide laser beam set at 8 W (32 W/sq cm). Each tissue "weld" withstood 40 cm H2O of peak ventilation pressure without leak. At the time of reoperation three weeks later, there was apparent complete healing of the pulmonary surface. No air leaks were present. Histologic examination showed a small zone of amorphous coagulated pleura and lung overlying a zone of minimal atelectasis. Normal lung was present within 150 mu of the laser seal. This new technique was performed safely and easily with currently available carbon dioxide lasers in the laboratory. It is presently undergoing intraoperative trials in a controlled clinical setting.

The effects of isoproterenol and dopamine on regional myocardial blood flow after stenosis of circumflex coronary artery.

The effects of isoproterenol and dopamine on regional myocardial blood flow were studied in 10 open-chest dogs after acute stenosis of the proximal circumflex coronary artery. Blood flow was determined by the radioactive microsphere technique. Isoproterenol led to a homogenous increase in blood flow in the normal myocardium. In the myocardium with compromised coronary blood flow, isoproterenol led to a relative subendocardial ischemia. This occurred despite increased aortic flow and peak left ventricular dp/dt. Dopamine also increased aortic flow and peak left ventricular dp/dt, but it did not cause regional myocardial ischemia. The findings suggest that dopamine is the preferable inotropic agent in managing low cardiac output in patients with significant coronary artery disease.

Effects of dipyridamol and methylprednisolone on intimal thickening in vein grafts.

Fibrous intimal proliferation severe enough to produce occlusion has been observed in vein segments used for aorta-coronary bypass grafts. In an attempt to improve graft patency and decrease intimal fibrous thickening, animals with vein grafts were treated with dipyridamole or methylprednisolone for 8 to 12 weeks. Femoral vein segments were used to bypass the femoral artery in 36 dogs. Thirty-four of these grafts were patent at 8 weeks, with no statistically significant differences between control and drug treatment groups. Intimal thickness measurements were taken at three different points along the graft: proximal (upstream end), middle,and distal (downstream end). Dogs treated with methylprednisolone had significantly less intimal thickening (214 versus 125 mu, p less than 0.05) than did control animals in the middle of the veins but there was no difference in thickness measurements at the proximal and distal ends. Dipyridamole-treated animals did not differ from control dogs. Although these data show decreasing intimal thickening in the middle of grafts with methylprednisolone therapy, the intimal thickness was still considerably greater than normal. The lack of response near the anastomotic sites suggests that clinical application of either agent to improve long-term patency is unwarranted.

Tricuspid regurgitation. A comparison of nonoperative management, tricuspid annuloplasty, and tricuspid valve replacement.

The best means of managing tricuspid regurgitation associated with mitral or mitral and aortic valve disease is still to be determined. During the period 1972 to 1974, we treated 76 patients who had tricuspid regurgitation along with associated valvular dysfunction. Patients with mold regurgitation were treated conservatively, those with moderate regurgation underwent annuloplasty, and those with severe regurgitation had tricuspid valve replacement. We found the results to be less satisfactory in the group treated by annuloplasty than in the other two groups. We still manage conservatively those patients with mild regurgitation, but we believe it appropriate to replace the valve in an increasing number of subjects who have tricuspid regurgitation of moderate severity.

The contribution of atrial contraction to right heart function before and after right ventriculotomy. Experimental and clinical observations.

Effective atrial contraction was abolished by simultaneous atrial and ventricular (A-V) pacing in an acute canine preparation. At constant cardiac output, aortic pressure, and heart rate, only a small rise (1.4 mm. Hg) in mean right atrial pressure was observed before vertical right ventriculotomy, but a larger rise (9.5 mm Hg) occurred after ventriculotomy (p less than 0.01). Right heart failure with tricuspid regurgitation was induced after ventriculotomy by volume overload and A-V pacing. Restoration of atrial contraction (sequential A-V pacing) eliminated regurgitation and lowered average mean right atrial pressure from 22 to 4 mm. Hg (p less than 0.001). After right ventriculotomy, loss of atrial contraction at a constant right atrial pressure resulted in a 42 per cent reduction in cardiac output. In 8 patients who had had right ventriculotomies, abolition of effective atrial contraction by A-V pacing caused an average reduction in cardiac output of 22 per cent, whereas cardiac output fell only 5 per cent in 5 control patients (p less than 0.01).

Serial assessment of left ventricular performance following coronary artery bypass grafting. Early postoperative results with myocardial protection afforded by multidose hypothermic potassium crystalloid cardioplegia.

Forty patients who recently underwent coronary artery bypass graft (CABG) operations had serial hemodynamic and scintigraphic studies. Multidose hypothermic potassium crystalloid cardioplegia was used for myocardial protection and newer techniques in anesthetic management and perioperative patient care were also employed. The method of equilibrium cardiac gated blood pool (GBP) scintigraphy was used to obtain perioperative changes in global ejection fraction (EF) and regional wall motion (RWM). Ninety percent of patients displayed a decrease in EF 2 hours postoperatively when compared to their preoperative values. This change was also associated with a fall in cardiac index (CI) and left ventricular stroke work index (LVSWI). Twenty-four hours postoperatively, EF and CI recovered to preoperative levels, but LVSWI remained depressed. Seven days postoperatively, global EF had improved to a value greater than the preoperative one (50% +/- 3% versus 57% +/- 4%, p < 0.05). Perioperative changes in RWM followed the same pattern as EF, but recovery in this index of regional contractility was faster than EF, since maximal improvement was observed 24 hours postoperatively. Thus transient left ventricular dysfunction is common immediately after CABG, but recent advances in myocardial protection and perioperative management are associated with short-term increases in regional and global left ventricular function documented by noninvasive GBP imaging.

Comparative study of warfarin versus antiplatelet therapy in patients with a St. Jude Medical valve in the aortic position.

To determine the necessity of long-term warfarin anticoagulation after St. Jude Medical aortic valve replacement in adults, we evaluated the risks of thromboembolism, valve thrombosis, anticoagulant hemorrhage, and sudden cardiac death in two groups of patients. Group I consisted of 41 patients treated with conventional long-term warfarin therapy. Forty-two patients in Group II were treated primarily with antiplatelet therapy (aspirin, dipyridamole, or both); 17 of these patients received warfarin for a short time postoperatively and seven others received it intermittently during the study period. The groups were similar with respect to age, sex, associated cardiovascular disease, and length of follow-up (mean 29 months per patient). In the warfarin-treated group, three late sudden deaths occurred, one of which was preceded by a cerebrovascular accident, for a cardiac mortality of 2.7% per patient-year. There were eight major nonfatal complications (7.3% per patient-year), of which four were hemorrhagic and four embolic. In Group II, there was one sudden cardiac death (1.1% per patient-year) and four major complications occurred (3.2% per patient-year). Two of the complications were embolic and two were episodes of valve thrombosis, both necessitating reoperation. Although the incidence of serious morbidity in the warfarin-treated group was twice that of patients treated with antiplatelet therapy, there were no statistically significant differences in the rates of sudden death or major complications. These data suggest that antiplatelet therapy may be as effective as warfarin in preventing embolism from the St. Jude Medical valve in the aortic position. Valve thrombosis occurred in two patients, both receiving antiplatelet therapy (2.2% per patient-year). Whether this type of valve failure can be prevented by warfarin remains in question.