Diagnosis of inherited von Willebrand disease: comparison of two methodologies and analysis of the discrepancies.

Diagnostics of von Willebrand disease (VWD) includes assessment of factor VIII (FVIII) coagulant activity, von Willebrand factor (VWF) antigen (VWF:Ag) and VWF ristocetin cofactor activity (VWF:RCo), and more specific tests as multimeric and genetic analyses are necessary for the correct VWD classification. The ACL AcuStar analyzer introduces chemiluminescence (CL) technology in detection of VWD with automated VWF:Ag and VWF:RCo assays. Compare VWF:Ag-ELISA and VWF:RCo by aggregometry conventional assays with new CL VWF:Ag-IL and VWF:RCo-IL assays, investigate the ability to make accurate VWD diagnosis and concordance with multimeric and genetic analyses. 146 patients with congenital VWD (51 Type 1; 34 Type 2A; 16 Type 2B; 31 Type 2M; 5 Type 2N; 9 Type 3) and 30 healthy normal subjects were included. A comparison was made between CL and conventional methods. Diagnostic evaluation included: VWF:RCo/VWF:Ag ratio, multimeric distribution (sodium dodecyl sulfate [SDS]-agarose gel) of VWF and genetic analysis in 110 of 146 patients. CL and conventional methods revealed good correlation. Kappa test agreement diagnosis was >0.8. CL diagnostic sensitivity was 100% and specificity 97%. Multimeric and genetic analysis were of help in clarifying 13 discrepancies of diagnosis between methods, of which six discrepancies were explained by lack of conventional methods' sensibility. CL methodology can detect VWD and discriminate between type 1, 3 and variant forms and offers an automated, faster, sensitive and less cumbersome method when compared to conventional assays, in particular VWF:RCo by aggregometry. In some cases, even with all phenotype and genetic analyses, discrepancies exist in the classification of VWD.

Complex Congenital Heart Disease: Is Heart Transplantation an Option?

INTRODUCTION: Within the heart transplant (HT) population, few patients have complex congenital heart disease (CHD) underlying disease. Our objective is to assess the complications and follow-up of patients with CHD transplanted in our center (1991-present). MATERIAL AND METHODS: Retrospective analysis of patients older than 14 years old with CHD and HT. Clinical and surgical variables were analyzed. RESULTS: Ten patients (age 25 ± 7 years old, 60% male) were analyzed, which represents 2.2% of the entire series of HT; 9 of the 10 patients were electively transplanted and 1 was under support with extracorporeal membrane oxygenation. Compared with the rest of the transplanted patients, patients with CHD had a lower median age (25 [25-36] vs 53 [15-69]; P < .009); more cardiac surgeries prior to HT (100% vs 14.4%; P < .001); a lower percentage of cardiovascular risk factors (CVRF; 0% vs 60%; P < .001). The left ventricle ejection fraction also showed statistically significant differences (33.5 [12-67] vs 20 [6-70]). CONCLUSIONS: Our patients with CHD and HT are younger and have less CVRF and more cardiac surgeries, which highlights that it is a subgroup with clear clinical differences in its comorbidity and pretransplantation assessment. They also require longer extracorporeal circulation time, more hours of intubation, and more days in the intensive care unit. Primary graft failure is more common in patients with CHD. Therefore, survival at 1-month follow-up is lower than the rest of the series and equalizes after the year of follow-up. This long-term survival reaffirms the possibility of HT in CHD despite the fact that its postoperative period is more difficult.

Prognostic Value of Blood Panel Parameters in Patients With Dilated Cardiomyopathy and Advanced Heart Failure.

BACKGROUND: Patients with dilated cardiomyopathy (DCM) and left ventricular dysfunction have a varied clinical course, not only dependent on left ventricular ejection fraction (LVEF) and symptoms. Finding prognostic markers for stratification in these 2 conditions is a critical area of research. Our aim was determine the prognostic value of blood panel basic parameters. METHODS: We analyzed all patients with idiopathic or familial DCM and LVEF <30% coming to our heart failure unit for evaluation for non-urgent heart transplant during the period of 2009 to 2011. With 5 years of follow-up data, we could study the prognostic value of blood panel parameters. Moreover, we determined the combination of platelet count and neutrophil to lymphocyte ratio score from the BIOSTAT-CHF study. RESULTS: Eighty-seven patients were included in the study. After 5 years follow-up, 49 patients (57%) remain alive (group A) and 38 (43%) either died or needed a heart transplant. There were no differences between groups with regard to age or sex. Patients with good progress showed a lower red cell distribution width (RDW), a higher lymphocyte count, and a lower neutrophil/lymphocyte ratio in the initial blood panel. An RDW ≥15% was associated with long-term mortality or heart transplant. CONCLUSION: A basic blood panel could be a useful tool in assessing patients with heart failure. Larger studies are necessary to confirm our findings. A multimarker strategy could also be useful for stratification of patients with advanced heart failure.

Preoperative Cardiac Assessment of Patients Undergoing Orthotopic Liver Transplantation: Experience in One Center.

Preoperative cardiac evaluation of patients undergoing liver transplantation is not well established. Stress testing is used in many centers, and clinical guidelines suggest its use. However, the specificity and sensibility of stress echocardiography to predict coronary lesions have been very low in some studies. Moreover, it has a low positive predictive value to predict complications after liver transplantation. We retrospectively analyzed 143 patients who underwent liver transplantation in our center and report our experience in the use of stress echocardiography. We describe cardiac complications during and after liver transplantation. Low prevalence of ischemic heart disease in asymptomatic patients undergoing liver transplantation make stress testing useless in risk stratification because it has a low positive predictive value. So the risk stratification of these patients before liver transplant surgery remains a challenge.

Effect of thiouracil upon canine arterial elastic tissue.

Unlike some other mammalian species, the dog is relatively resistant to the development of elevated levels of serum cholesterol after prolonged cholesterol feeding. This may be overcome by suppressing thyroid activity with thiouracil. Information regarding possible activity of thiouracil itself upon the arterial tissues is almost nonexistent. The present investigation was undertaken to test whether this drug has any such action, especially upon the arterial elastic tissues. Destructive changes were observed in arterial elastic tissues in dogs given thiouracil for three and six months. The changes consisted of accentuation of the elastic fibrillar components, formation and subsequent coalescence of clefts, and fragmentation and ultimate "dissolution" of the elastic elements. The results suggest that thiouracil may exert a damaging effect upon the arterial elastic fibers; thus, it is possible that one of the mechanisms by which thiouracil and cholesterol administration induces experimental atherosclerosis in the dog is by elastic tissue destruction, possibly promoting the subsequent lipid accumulation in the arterial wall.

Ultrastructure of proteoglycans in human renal arteries from end stage renal disease.

Although glycosaminoglycans, particularly proteoglycans, have been characterized biochemically in normal and diseased arteries, little is known regarding their ultrastructural characteristics in human arteries. The observations reported here were made in renal arteries from nephrectomy specimens from patients with endstage kidney disease and hypertension. By light microscopy, the diffusely thick intima is characterized by small, slender smooth muscle cells embedded in a finely fibrillar, strongly alcian-blue positive, intercellular matrix. Ultrastructurally, there is a loose meshwork of collagen fibrils, elastic units and abundant fibrillogranular units staining strongly with ruthenium red and identified as proteoglycans. These consist of ovoid or diamond-shaped electron-dense granules about 300-500 A in diameter, having fine filamentous processes.

The cell population of aortic fatty streaks in African green monkeys with special reference to granulocytic cells. An ultrastructural study.

It is generally accepted that the cell population of naturally occurring and experimental atherosclerotic lesions is constituted by smooth muscle cells and non-myogenic foam cells of monocytic origin. In the present investigation we studied aortic fatty streaks from cholesterol-fed African green monkeys. In addition to the traditionally recognized cell types, the majority of the lesions examined contained intimal granulocytic cells identified by their ultrastructural characteristics and granular content as neutrophils, mast cells-basophils, and eosinophils. The neutrophils, and mast cells-basophils additionally contained numerous cytoplasmic lipid droplets. The consistent observation of these cell types in our material suggests that these granulocytic elements are part of the cell population of fatty streaks. The role of these cells is not clear as yet, but it is likely that the enzymatic activity of neutrophils such as lipase, phospholipases A and B, elastase and collagenase may play a role in the clearing of arterial lipid as well as in arterial wall remodeling. The content and release of heparin and histamine by basophils and mast cells may play a role in preventing thrombus formation and in promoting lipolysis. Eosinophil peroxidase may activate histamine release by basophils and mast cells. The cytoplasmic lipid accumulation by neutrophils, basophils and mast cells may in turn contribute to the population of foam cells in these lesions.

Effect of small-amplitude electrical activity on myocardial preservation in the cold potassium-arrested heart.

Recent reports indicate that small-amplitude electrical activity may be present in the cold potassium-arrested heart. Twenty-four mongrel dogs were placed on cardiopulmonary bypass and cooled to a rectal temperature of 26 degrees C. Myocardial preservation was provided with a combination of systemic hypothermia 26 degrees C. potassium (20 mEq/L) crystalloid cardioplegic solution (10 ml/kg) infused initially and every 30 minutes during 90 minutes of ischemic arrest, and topical hypothermia. Myocardial temperature was maintained between 8 degrees and 10 degrees C. Electrical activity and transmural myocardial temperature were monitored with specially designed plunge electrodes. Left ventricular stroke work index, cardiac index, and maximum rate of rise of left ventricular pressure were measured before bypass and 45 minutes after ischemic arrest. Biopsy specimens were taken before bypass and at 15 and 45 minutes after ischemic arrest. The specimens were used to measure adenosine triphosphate and to analyze electron microscopic ultrastructure. Small-amplitude electrical activity was present in 16 of 24 animals during cardioplegic arrest. Cardiac index decreased 18 ml/min/kg (not significant), left ventricular stroke work index fell by 0.28 +/- 0.1 gm-m/beat/kg (p less than 0.007), and maximum rate of rise of left ventricular pressure decreased 409 mm Hg/sec (p less than 0.01) in the eight animals without small-amplitude electrical activity. Adenosine triphosphate concentration was unchanged and electron microscopic ultrastructure was well preserved. In contrast, small-amplitude electrical activity (16 animals) resulted in a decrease in cardiac index of 67 ml/min/kg (p less than 0.001), a decrease in left ventricular stroke work index of 0.79 +/- 0.8 gm-m/beat/kg (p less than 0.001), and a fall in maximum rate of rise of left ventricular pressure of 775 mm Hg/sec (p less than 0.001). Adenosine triphosphate concentration decreased from 25 to 21 mumol/gm (p less than 0.04) and electron microscopic ultrastructure was poorly preserved (p less than 0.001). This study demonstrates that small-amplitude electrical activity in the cardioplegia-arrested heart at 10 degrees C impairs myocardial preservation.

Is a left ventricular vent necessary for coronary artery bypass operations performed with cardioplegic arrest?

The need for ventricular venting with hypothermic cardioplegic arrest is controversial. We report an evaluation of the need for left ventricular venting in a canine model that closely simulates conditions during routine coronary artery bypass grafting (CABG). Thirty-five dogs were placed on cardiopulmonary bypass for 60 minutes of hypothermic cardioplegic arrest (18 vented, 17 nonvented) and then reperfused for 30 minutes. Myocardial temperature and left atrial pressure (LAP) were recorded continuously. Before and 30 minutes after hypothermic cardioplegic arrest, left ventricular function curves were generated (six vented, six nonvented), and biopsy specimens of the left ventricle were taken for adenosine triphosphate (ATP) determinations (11 vented, 10 nonvented) and semiquantitative grading of mitochondrial ultrastructure (six vented, six nonvented). LAP in nonvented dogs was 7.4 mm Hg during hypothermic cardioplegic arrest and 5.0 mm Hg during reperfusion. Temperature during hypothermic cardioplegic arrest was 12.3 degrees C in vented dogs and 11.3 degrees C in nonvented dogs (p = 0.5). There were no differences in left ventricular function or preservation of mitochondrial ultrastructure between vented and nonvented dogs. ATP after hypothermic cardioplegic arrest was 96.6% of control (4.30 microM/gm) in vented dogs and 94.6% (4.37 microM/gm) in nonvented dogs (p = 0.7). The absence of left ventricular venting did not lead to ventricular distention or more rapid rewarming. These data in vented dogs and nonvented dogs strongly support the belief that left ventricular venting is not necessary during routine CABG.

Prevention of myocardial electrical activity during ischemic arrest with verapamil cardioplegia.

The effect of potassium cardioplegia and potassium cardioplegia containing verapamil hydrochloride on myocardial preservation and electrical activity during prolonged aortic occlusion was examined in 40 adult mongrel dogs. Twenty-four animals (Group 1) received potassium cardioplegia, and 16 animals (Group 2) received potassium verapamil cardioplegia. Potassium or potassium verapamil cardioplegia, 10 ml per kilogram of body weight, was administered after application of the aortic cross-clamp and at 30-minute intervals during the 90-minute arrest. Myocardial temperature was maintained within a range of 8 degrees to 10 degrees C with topical ice saline solution, and electrical activity was monitored with specially designed plunge electrodes. Plunge electrode activity was recorded from the myocardium during arrest in 16 of the 24 animals in Group 1; no electrical activity was present in the animals in Group 2 (p less than .001). The addition of verapamil to potassium cardioplegia increased the tolerance of the myocardium to prolonged ischemia and resulted in less depletion of high-energy phosphate stores and better preservation of mitochondrial ultrastructure and left ventricular function. These data suggest that verapamil augments the preservation provided by potassium cardioplegia by initiating and maintaining a more complete electrical arrest.

Malakoplakia of kidney simulating renal neoplasm.

In a nine-year-old girl with renal hypertension and a urinary infection, angiographic studies of the left kidney suggested an intrarenal pheochromocytoma. After nephrectomy, the kidney was found to contain only a cystic lesion characterized by multiple small, friable excrescences. Under the light microscope these appeared to be formed by granulovacuolated macrophages. Electron microscopy showed intracytoplasmic inclusion identified as Michaelis-Gutmann bodies in various stages of formation. Images suggestive of degraded bacteria were also observed within phagolysosomes.

Neonatal renal failure and glomerular immaturity.

A case of acute renal failure in a neonate was observed in which there were no obvious predisposing factors. Renal biopsy showed marked glomerular immaturity with otherwise normal renal architecture. Light and ultramicroscopic abnormalities noted suggest that the glomerular immaturity caused an abnormally low glomerular ultrafiltration coefficient (Kf). An inadequate rate of glomerular filtration secondary to the low Kf could have precipitated the acute renal failure. The finding of isolated glomerular maturational arrest is a previously undescribed cause of neonatal renal failure.

Influence of systemic hypothermia on systolic and diastolic functional recovery after continuous warm antegrade blood cardioplegia.

Experimental observations in our laboratory indicate that myocardial recovery is similar following warm or cold antegrade blood cardioplegia when the core temperature is maintained at 37 degrees C. To determine the effects of hypothermia on myocardial recovery, 15 adult mongrel dogs were randomized to normothermic or hypothermic bypass (28 degrees C) during 60 min of continuous warm antegrade blood cardioplegia. The hypothermic group was rewarmed after releasing the aortic cross-clamp and bypass was discontinued at 30 min in both groups. Myocardial recovery was assessed at 60, 90, and 120 min after the arrest. Core temperature was maintained in the normothermic group but gradually decreased after bypass in the hypothermic group, reaching a low of 33.8 +/- 1 degrees C at 120 min. Myocardial functional recovery was preserved after normothermic bypass. The decrease in core temperature, however, that was observed after systemic hypothermia, was paralleled by significant decreases in the maximum rate of left ventricular pressure rise (dp/dt), the maximum elastance of the left ventricle, and preload recruitable stroke work. Diastolic function decreased slightly, but not significantly, during reperfusion following systemic hypothermia but was unaltered after normothermic bypass. Myocardial oxygen consumption was unchanged in both groups. Myocardial ultrastructure was preserved after normothermic bypass. In contrast, cellular oedema and mild ultrastructural changes were evident after systemic hypothermia. We therefore conclude that the use of systemic hypothermia during bypass is associated with lower core temperatures during early recovery which results in impaired functional recovery.

Effect of high-volume cardioplegia on small-amplitude electrical activity during cardioplegia arrest.

UNLABELLED: The effects of high-volume cardioplegia on the presence of small-amplitude electrical activity during cardioplegia arrest were investigated in 19 mongrel dogs. The animals were randomly assigned to receive either high-volume crystalloid cardioplegia (HV-plege) or crystalloid cardioplegia guided by continuous electrical monitoring (V-plege). Cardiac index, left ventricular stroke work index dp/dt, and myocardial oxygen consumption were measured before bypass and following 90 min ischemia and 45 min reperfusion. Biopsies were taken for measurement of adenosine triphosphate (ATP) and examination of myocardial ultrastructure. Nine animals received HV-plege, while the remaining 10 animals received cardioplegia guided by voltage criteria. Small-amplitude electrical potentials were recorded within 10-15 min after the infusion of cardioplegia in all animals receiving cardioplegia guided by voltage criteria. Electrical activity, however, was immediately abolished by reinfusion of cardioplegia. HV-plege reduced the incidence of small-amplitude electrical activity during cardioplegia arrest but did not prevent electrical activity. Left ventricular function and myocardial ultrastructure were better preserved when cardioplegia was guided by electrical monitoring. ATP decreased similarly in both groups following cardioplegic arrest, but myocardial oxygen consumption was significantly higher following the arrest in the V-plege group. CONCLUSIONS: HV-plege does not prevent small-amplitude electrical activity and may have adverse effects on myocardial metabolic and functional recovery.

Solitary condylomatous papilloma of the bronchus.

Two case reports of solitary bronchial papillomas are presented. The histologic features of the lesions are those of squamous papillomas exhibiting prominent condylomatous changes. Immunoperoxidase stains revealed the presence of human papillomavirus antigens in the koilocytotic cells. Ultrastructural studies demonstrated possible intranuclear viral-size particles. Solitary condylomatous papillomas of the bronchus should be distinguished from solitary bronchial squamous papillomas that do not have condylomatous features. The rationale for this separation is the likelihood of a viral origin for these condylomatous papillomas and their potential for malignant change.

Adult variant of congenital mesoblastic nephroma.

Congenital mesoblastic nephroma is a relatively rare tumor predominantly of childhood. Occurrence in adults is exceedingly rare and, to my knowledge, only two cases have been reported to date. This article pertains to a mesoblastic nephroma in a 41-year-old woman. The tumor was composed mainly of compact fibrocollagenous elements interspersed with areas containing immature tubules and occasionally glomeruloid structures. There was no evidence of capsular or renal invasion or cytological malignant features. It has been postulated that this neoplasm may represent a form of mature Wilms' tumor with a benign clinical course.

Glomerular calcinosis in sarcoidosis.

Glomerular lesions secondary to calcium deposition in sarcoidosis have not been previously described, to our knowledge. Five renal biopsy specimens from four patients with sarcoidosis were studied by light, electron, and immunofluorescence microscopy. In addition to interstitial granulomatous nephritis and nephrocalcinosis, which were seen in all cases, segmental glomerular lesions characterized by marked thickening and wrinkling of the glomerular capillary walls and basophilic appearance of the altered basement membranes were present in three of the cases. Electron microscopic examination of the lesions revealed dramatic alteration of the glomerular ultrastructure. Numerous single and coalescent calcific microspherules were present within the basement membrane, the paramesangial zone, and the mesangium. The findings of immunofluorescence were noncontributory. The structural alterations caused by calcinosis of the glomerulus may be responsible for some of the frequent renal function abnormalities seen in sarcoidosis.

Choriocarcinoma of the esophagus: histologic and cytologic findings. A case report.

The present report is that of a 40-year-old woman admitted with hematemesis and epigastric pain. Endoscopy revealed a fungating mass in the lower esophagus. Esophageal brushing revealed clustered and single malignant cells with ample cytoplasm, large bizarre nuclei and prominent, irregular nucleoli; the chromatin was irregular with clumping at the nuclear borders. Giant multinucleated malignant cells were numerous. These cells had nuclear molding and abundant acidophilic cytoplasm. Autopsy findings included a large tumor in the lower esophagus and metastases to lung, liver and kidneys. Microscopically, the fungating esophageal tumor and metastases were composed of cyto- and syncytiotrophoblastic elements. Choriocarcinoma of the esophagus is a rarity, and only two cases were found in the literature. The diagnosis, however, can be achieved by brush biopsy since the characteristic cyto- and syncytiotrophoblastic cells can be readily identified, provided that the possibility of this ectopic occurrence is recognized.

Adenocarcinoma of the urinary bladder: histologic, cytologic and ultrastructural features in a case.

A case of primary adenocarcinoma of the urinary bladder is presented, including the histologic, cytologic and ultrastructural studies. Cytologically, the diagnosis was substantiated by the presence of gland-like clusters of columnar epithelial cells and "signet-ring" cells. The neoplastic cells, whether single or in clusters, had large secretory vacuoles, hyperchromatic nuclei and prominent nucleoli. Ultrastructurally, the neoplastic cells appeared as rounded, distended structures, with markedly diminished surface microridges and plicae. In thin sections, the neoplastic cells showed a large cytoplasmic vacuole and an eccentric nucleus. An early diagnosis of primary bladder adenocarcinoma is of importance due to therapeutic and prognostic implications.

[Antibiotic sensitivity, serology and typing by pyocine in 154 cultures of Pseudomonas aeruginosa (author's transl)]. / Sensibilidad antibiótica, serología y piocinotipia de 154 aislamientos clínicos de Pseudomonas aeruginosa.

Pseudomonas infections continue to be an important problem in the hospital environment. Serious infections are always invariably associated with severe underlying conditions or with diminished host resistance. The increasingly resistance of strains and hospital epidemics favour the organism prevalence. During 1978, Pseudomonas aeruginosa was isolated in 154 cultures from a variety of biological samples in the hospital. Tests of biochemical identification, serological typing, and typing by pyocine production were carried out. Susceptibility to aminoglycosides and beta-lactamic antibiotics was also tested. Serological study demonstrated a higher incidence of 4 and 11 serotypes; 69.4 percent corresponded to type I when typing by pyocine production was carried out. No relationship between serotypes and pyocine-types has been found. Ticarcillin showed a greater activity than carbenicillin (minimal inhibitory concentration less than or equal to 16 micrograms/ml). Amikacin, tobramicin, sisomicin and gentamicin inhibited 83.7 percent, 73.6 percent, 70.7 percent and 69.4 percent of the isolated strains, respectively.