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.

Dissociation of osmoregulation from plasma arginine vasopressin levels following thermal injury in childhood.

Although the syndrome of inappropriate anti-diuretic hormone secretion has been recognised as a complication associated with burn and other trauma in adults, relatively little is known about its incidence in children. The objective of this study was to investigate whether it is a complication associated with burn injury in children. Plasma and urine levels of arginine vasopressin (anti-diuretic hormone), sodium and osmolality were measured in samples collected from 16 burn-injured children admitted to the burns unit of the regional children's hospital. No significant correlations were found between plasma vasopressin and plasma sodium or osmolality levels, but there were significant correlations between plasma vasopressin and urine osmolality, 36 (r=0.74, p=0. 009), 60 (r=0.92, p=0.000) and 84 h (r=0.84, p=0.001) after admission, respectively. There were also significant correlations between plasma sodium and plasma osmolality, 24 (r=0.7, p=0.005), 36 (r=0.57, p=0.04) and 84 h (r=0.84, p=0.004) after admission. The data suggest dissociation between the osmolar control of vasopressin secretion and vasopressin levels after burn injury in children, but do not support the incidence of inappropriate secretion of antidiuretic hormone.

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.

[Serum lipids and vitamins in senile macular degeneration]. / Serumlipide und -vitamine bei seniler Makuladegeneration.

P6e correlations between serum cholesterol, triglycerides and lipoproteins and serum vitamins A and E were tested in patients with age-related macular degeneration (AMD). Patients diagnosed as having "senile" macular degeneration who were not receiving medical treatment that would interfere with lipid or vitamin metabolism consecutively underwent-fundus photography and fluorescein angiography in a 6-month period. Cholesterol, triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), vitamin A and E were assayed using conventional methods (enzymatic and high-performance liquid chromatography). Sixty-four angiographies from 64 patients were evaluated. The clinical diagnosis was: "hard" drusen (n = 5), geographic atrophy (25), "soft" drusen (10), subretinal neovascularization and disciform scar (24). The percentage of pathological data was calculated: HDL, 89%; cholesterol, 84%; vitamin A, 75%, LDL, 66%; Vitamin E, 33%; triglycerides, 23%. The data differed somewhat between groups. The high prevalence of hypercholesterolemia in older age groups [3, 34] prevents cholesterol from being identified as a risk factor for AMD. Elevated levels of atherogenic LDL and reduced vitamin A are discussed versus "protective" HDL and vitamin E. In many of the AMD cases described, the cardiovascular risks of dyslipoproteinemia demand adequate therapy.

[The effect of carteolol. Prolonged and increased effect by liposome suspension]. / Die Carteololwirkung. Verlängerung und Verstärkung durch Liposomensuspension.

Liposomes are small lipid vesicles capable of trapping beta-blockers such as carteolol within their bilayer structure, the advantage being improved drug action, prolonged action time, and a reduction in drug concentration. In a prospective, randomized double-blind trial, carteolol 2%, liposomes (frozen and thawed multilamellar vesicles, FAT-MLVs), or carteolol 2% suspended with FAT-MLVs was applied to 25 eyes of 25 patients per group in a single 20 microliters dose. Intraocular pressure was measured for 3 days. A significant reduction in the IOP was observed in the patient groups receiving carteolol and carteolol suspended with liposomes. Moreover, improved action and prolongation of drug action was noted in the carteolol/MLV group as compared to carteolol treatment alone. Hence, carteolol 2% is suitable for reduction of IOP, but a reduction of drug concentration can be achieved by suspension with liposomes, thus reducing the side effects.

[Canthaxanthin retinopathy. Follow-up of over 6 years]. / Canthaxanthin-Retinopathie. Verlaufskontrolle nach über 6 Jahren.

After long-term treatment with high dosages, canthaxanthin causes a characteristic retinopathy with circular, macula surrounding crystals. As changes in retinal functionning disappear relatively easily after withdrawal of the drug, the crystals dissolve rather slowly--over about several years. Five patients showing a profound crystalline retinopathy were re-examined with an average of 69.7 months after withdrawal of the canthaxanthin-containing drug. Three of the patients were treated for erythropoetic protoporphyria (EPP) with Phenoro (2/5 beta-carotene, 3/5 canthaxanthin), two sisters took a canthaxanthin-containing formulation (1/8 beta-carotene, 7/8 canthaxanthin) for cosmetic reasons. Two female patients complained about an increased glare sensitivity, which was explainable for one of them with a subcapsular cataract. The retinal crystals decreased quite differently. Minor deffects of the retinal pigment epithelium remained unchanged in two patients. They increased slightly in the female patient with the smallest crystal formation but highest plasma cholesterol. Shortly after withdrawal of the drugs usually an increase of a-wave amplituded of the electroretinograms was found. The a-waves returned to normal and the b-wave amplitudes showed an increase up to the final control paralleling the reduction of the retinal crystals. A- and b-wave peak latencies which were prolonged under treatment returned to normal.

Carteolol incorporated into FAT-MLV liposomes: prolonged and decreased reduction of IOP.

Liposomes are used as carries providing a prolonged and improved drug action. They are capable of trapping beta-blockers such as Carteolol. In a randomized prospective double-blind clinical trial, Carteolol 2% suspended with frozen and thawed multivesicular large vesicles (FAT-MLV), FAT-MLV, and Carteolol 2% were applied to normal (slightly cataracterous) eyes and immediately after extracapsular cataract extraction or phakoemulsification with implantation of a posterior chamber lens in a standard procedure. Twenty-five patients were included in each group. Intraocular pressure (IOP) was measured for 3 days using applanation tonometry. In the normal eyes, a significant reduction of IOP was found for the patients receiving Carteolol and Carteolol MLV suspension. Moreover, an improved action and a prolongation of drug action was registered in the Carteolol/MLV group as compared to Carteolol treatment alone. After cataract operation, the control groups showed a significant increase in IOP. Carteolol produced a constant level of IOP but the Carteolol/MLV suspension showed a stronger decrease after ECCE and a still stronger decrease after phakoemulsification. Hence, Carteolol is suitable for the reduction of IOP but a Carteolol/MLV suspension is more effective, providing the possibility of a single application of a low-dose beta-blocker after cataract extraction with posterior chamber lens implantation.

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)

Living-related lobar lung transplantation in beagle puppies.

Unilateral lung transplantation has provided effective short-term therapy in adults with end-stage lung disease. Rejection continues to be the most common cause of transplant failure. Living-related lung transplantation may decrease the recipient immune response. The purpose of this study is to test the technical and physiological feasibility of living-related lobar lung transplantation from adult beagles into beagle puppies in a chronic model. Twenty purebred adult beagle donors underwent left thoracotomy with harvest of the left lower lobe using cold perfusion of the pulmonary artery and cold immersion. Twenty recipient purebred beagle puppies from the same colony underwent left thoracotomy, left pneumonectomy, and implantation of the donor adult lobe. Anastomoses were performed in sequence: pulmonary vein to left atrium, bronchus, pulmonary artery. Postoperative immunosuppression was with Cyclosporine. Respiratory function of the implanted lobe was evaluated by pulmonary angiography and during balloon occlusion of the right pulmonary artery with arterial blood gases 1 month after transplantation. Ten recipient puppies died of rejection (4), infection (3), or bronchial dehiscence (3) prior to angiography. Seventeen pulmonary angiograms in 10 surviving animals showed normal left pulmonary arterial blood flow (2), diminished left pulmonary arterial flow (5), and occluded left pulmonary artery (3). In two recipients balloon occlusion of the right pulmonary artery was performed and respiratory function was maintained solely by the transplanted lobe for 2 days in one recipient and for 30 minutes at 1 month and 2 months postimplant in a second recipient. Living-related lung transplantation of adult beagle lobes into pneumonectomized beagle puppies is technically feasible. High mortality rates in a chronic model are related to infection and rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

New uses of the laser in thoracic and cardiovascular surgery.

Lasers have been accepted in general thoracic surgery as resectional tools which allow precise hemostasis and maximal salvage of normal lung tissue. Used endoscopically, with or without associated photodynamic therapy, we have provided acceptable palliation in some patients with obstructing tumors of the tracheobronchial tree and esophagus. Cardiovascular uses of the laser have been under extensive investigation at our medical center for many years. We have demonstrated that laser-assisted anastomosis of small vessels is possible, that early tensile strength and patency are excellent, but that long-term aneurysm formation is excessive. In addition, CO2 laser injury of the arterial intima leads to a marked increase in atheromata formation in animal models of atherosclerosis; this may be eliminated with the excimer laser. We have begun using the excimer laser to open obstructed peripheral and coronary arteries. New technology is emerging which allows dual fiber catheters which allow identification of tissue in an artery, ie calcium, atheromata, clot, media, etc. and instantaneous computer sensing/integration which initiates "fire" or "no fire" signals in the enclosed laser system, thus decreasing the chance of vessel perforation. These technologies, in association with balloon angioplasty, intravascular stents, and atherectomy devices are offering exciting alternate therapy for patients with obstructing atherosclerosis.

Aggressive blood conservation in coronary artery surgery: impact on patient care.

Data on 100 consecutive non-emergency coronary artery bypass (CABG) patients were analyzed retrospectively. Sixty-nine patients received no homologous blood (Group I). Thirty-one patients received a total of 118 units of blood products averaging 2.23 units of red cells (Group II). The average red cell transfusion rate for all patients was 0.7 units per patient. The median age for Group I was 61 and Group II was 68 years (p less than 0.05). The average number of grafts was the same for both (3 per patient) with 75% of Group I and 58% of Group II receiving internal mammary artery (IMA) grafts (p less than 0.05). Twelve of the Group II patients who received intraoperative transfusions on cardiopulmonary bypass to maintain adequate hemoglobin levels were older and had lower admission hematocrits: 36 +/- 0.8% compared to 41 +/- 0.5% for all other patients (p less than 0.05). Average postoperative blood loss was 889 +/- 38 ml for Group I and 1077 +/- 104 ml for Group II (p less than 0.05). Increased hemorrhage was correlated with bypass time and IMA use but not with preoperative heparin administration, pre-existing risk factors (diabetes, hypertension, etc.), bleeding time, post-bypass clotting time, age or number of grafts. Two patients in Group II and none in Group I required exploration for excessive postoperative hemorrhage. Mortality rate was 2% (both in Group II, neither transfusion related). Discharge hematocrits were the same for all at 29.4 +/- 0.4%. Among anemia-related postoperative symptoms, only sinus tachycardia was significantly higher in Group I (20%) compared to Group II (6.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical experience with portable cardiopulmonary bypass in cardiac arrest patients.

To evaluate the use of portable cardiopulmonary bypass as a resuscitative tool and its impact on long-term survival of patients in cardiac arrest, we reviewed the results of 32 consecutive patients resuscitated by cardiopulmonary bypass for cardiac arrest or severe hemodynamic compromise at Northwestern Memorial Hospital over a 2-year period. Overall survival was 12.5%. Only 1 (3.4%) of the 29 patients who had cardiac arrest survived and left the hospital. All 3 patients who had severe hemodynamic compromise but not cardiac arrest were long-term survivors. Our study suggests that portable cardiopulmonary support systems used as a resuscitative tool do not prolong the survival of most cardiac arrest patients but may be useful for patients with shock due to mechanical causes and for those with profound hemodynamic compromise due to ischemia or myocardial infarction. Portable heart-lung machines can provide patients with excellent hemodynamic support; however, neurological or cardiac recovery is unlikely once cardiac arrest occurs.

Interposition of the thymus as a pedicled flap in tracheal reconstructive surgery.

Thymus was interposed in six patients following tracheal reconstruction: three tracheo-innominate fistula repairs, two resections for stenosis, and one repair of a membranous tear during esophagectomy. The two resections for stenosis were elective; the others were emergent repairs. This gland, readily accessible in the upper mediastinum, is easily dissected from the pleura and pericardium and separated into two lobes. Pedicles based at the thoracic inlet measure between 15 and 20 cm by 4 cm. Each lobe receives independent arterial blood supply and venous drainage which remains intact even if the innominate vein must be divided to effect tracheal repair. All patients survived the perioperative period. The patient with the tracheo-innominate fistula died 1 month later. No patient had evidence of further vascular complications or tracheal anastomotic leak even though one patient developed a long segment of necrotic trachea. Reinforcement following tracheal reconstruction is important in preventing complications from anastomotic leak or vascular erosion. The pedicled thymus gland is an excellent, readily available interposition flap for emergent or elective tracheal reconstruction.

Implications of prosthetic valve implantation: an 8-year follow-up of patients with porcine bioprostheses.

Nurses in cardiovascular critical care settings routinely care for patients with implanted valvular prostheses. The presence of an artificial valve substitutes a new disease state for the preexisting valvular disease. Five hundred nine patients who underwent cardiac valve replacement with porcine bioprostheses and who were followed for a total of 1633 patient-years provide the data base for discussion of long-term survival, functional capacity, and morbidity associated with valvular prostheses. Seventy-two percent of patients survived 5 years after operation. New York Heart Association functional class was improved in 84%. Three major types of morbidity were documented: thromboembolism, endocarditis, and valve failure. Cardiovascular nurses should be familiar with the implications of valvular prostheses to provide appropriate patient education and to facilitate the prompt detection and treatment of valve-related complications.

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.