Correlates of myocardial oxygen demand measured by positron emission tomography in the hypertrophied left ventricle

BACKGROUND: The aim of this study was to identify the best correlate of myocardial oxygen demand (MVO(2)) in patients with hypertension induced left ventricular hypertrophy (LVH), and to examine whether relationships between these surrogates and MVO(2) differed between patients with LVH and control subjects. METHODS: We measured MVO(2) by positron emission tomography using carbon-11 acetate in 20 patients and 10 normotensive control subjects, and compared the relationships between commonly used surrogates and MVO(2). RESULTS: With the exception of diastolic blood pressure, the same variables correlated with resting MVO(2) in the patients and control subjects. CONCLUSIONS: The best correlate of resting MVO(2) in the patients with hypertension induced LVH was the stress-mass-heart rate product.     

The tyrosine kinase NPM-ALK, associated with anaplastic large cell lymphoma, binds the intracellular domain of the surface receptor CD30 but is not activated by CD30 stimulation

The heterogenous group of anaplastic large cell lymphomas (ALCLs) is characterized by expression of the Ki-1/CD30 antigen, a member of the tumor necrosis factor receptor superfamily. About 40 to 50% of cases diagnosed as ALCL contain a specific chromosomal rearrangement, t(2;5)(p23;q35), resulting in expression of the chimeric tyrosine kinase NPM-ALK. As NPM-ALK-positive lymphomas define a distinct subtype within the group of ALCL, the chimeric protein might be responsible for certain pathogenetic and clinicopathologic characteristics. To better elucidate the function of NPM-ALK, we investigated a possible mechanism for regulation of its activity. We demonstrate that NPM-ALK specifically binds to the intracellular domain of the cytokine receptor CD30. In vitro binding assays revealed that the ALK portion of NPM-ALK mediates interaction of the two proteins. Stimulation of the CD30 receptor by cross-linking with immobilized anti-CD30 antibody results in complete growth inhibition of Karpas 299, an NPM-ALK-positive ALCL cell line, but does not alter proliferation of HDLM-2, a Hodgkin's lymphoma-derived cell line lacking t(2;5). Western blot analysis of coimmunoprecipitated CD30 and NPM-ALK proteins from stimulated Karpas 299 cells showed that the interaction of the proteins is not modified by stimulation. Activation of CD30 neither enhanced NPM-ALK activity measured by autophosphorylation of the chimeric tyrosine kinase nor phosphorylation of phospholipase C-gamma, an NPM-ALK substrate. We conclude that NPM-ALK is not stimulated by CD30 activation, but exists as a constitutively hyperactivated protein. Interaction with CD30 may extend the subcellular localization of NPM-ALK to the microenvironment of membrane-associated proteins.     

Sequelae after modified Fontan operation: postoperative haemodynamic data and organ function.

OBJECTIVE: To investigate the specific sequelae of the Fontan operation, and particularly the potential sequelae of chronically elevated systemic venous pressure. DESIGN: A retrospective analysis of clinical and haemodynamic data and evaluation of organ function in 80 surviving patients undergoing modified Fontan operation for various forms of underlying functionally univentricular hearts. PATIENTS: 65 patients (81%) who had undergone a total cavopulmonary anastomosis and 15 an atriopulmonary anastomosis. Follow up ranged from 12 to 106 months (mean 54 (SD 23) months). RESULTS: 62 patients underwent postoperative cardiac catheterisation (mean systemic venous pressure 10.5 (2.5) mm Hg and cardiac index 3.1 (0.7) l/min/m2). Older age at operation was significantly correlated with both higher systemic venous pressure and lower cardiac index. Atrial arrhythmia was documented on Holter electrocardiogram in 17%. Protein losing enteropathy (with abnormal alpha 1-antitrypsin clearance) was found in 2/80 patients (2.5%). Ten patients had hypoproteinaemia, with a significantly higher incidence in patients after total cavopulmonary anastomosis and young age at operation. Liver function tests reflecting liver synthesis and metabolism were normal in all, whereas mild cholestasis was found in nearly 30%-predominantly in patients with a cardiac index of < 3 l/min/m2 (P = 0.045). Five patients (6.2%) developed atrial thrombosis. Coagulation factor analysis in 44 patients showed protein C deficiency in 11 (25%); laboratory signs of activation of the coagulation system were found in four of these (9%). None of the abnormal laboratory indices was significantly related to underlying cardiac malformation, postoperative systemic venous pressure, or follow up interval. CONCLUSIONS: A high proportion of clinically asymptomatic patients had abnormal laboratory findings on mid-term follow up. Detailed evaluation of organ function is necessary to detect the need for further diagnostic procedures before clinical symptoms develop.     

Immunologic differentiation of proteins in the surfactant system of the lung.

Immunoelectrophoresis revealed the following four protein components in the lung surfactant system of guinea-pigs: albumin, transferrin, IgG, and an organ-specific protein migrating in the beta-globulin range. These proteins probably take part in the formation of the hypophase of the alveolar lining layer and thereby influence the surface properties of the alveolar air-liquid interface.     

Oesophageal and gastric motility disorders in patients categorised as having primary anorexia nervosa.

Gastrointestinal motor function in patients with primary anorexia nervosa has rarely been investigated. We studied oesophageal motor activity in 30 consecutive patients meeting standard diagnostic criteria for primary anorexia nervosa (Feighner et al; DSM III). Seven were found to suffer from achalasia instead of primary anorexia nervosa, one from diffuse oesophageal spasm and one from severe gastro-oesophageal reflux and upper oesophageal sphincter hypertonicity, while partly non-propulsive and repetitive high amplitude, long duration contractions prevailed in the lower oesophagus of another six. In four patients with oesophageal dysmotility not responding to therapy and in 12 of 15 patients with normal oesophageal manometry, gastric emptying of a semisolid meal was studied. Emptying was normal in only three but markedly delayed in 13 cases (half emptying times 97-330 min, median: 147 min, as compared with 21-119 min, median: 47 min, in 24 healthy controls). In eight patients, the effects of domperidone 10 mg iv and placebo were compared under random double blind conditions. Half emptying times were shortened significantly (p less than 0.01) by domperidone. Conclusions: symptoms of disordered upper gastrointestinal motor activity may be mistaken as indicating primary anorexia nervosa; clinical evaluation of patients with presumed primary anorexia nervosa should rule out the possibility that disordered oesophageal motor activity underlies the symptoms; delayed gastric emptying is a frequent feature in primary anorexia nervosa and might be returned to normal with domperidone.     

Respiratory failure following anti-lung serum: study on mechanisms associated with surfactant system damage

Within 2 minutes intravenous anti-lung serum (ALS) into guinea pig induces a respiratory failure that is fatal within 30 min. The relationship between surfactant, alveolar-capillary permeability and respiratory failure was studied. Within two minutes ALS induced a leak in the alveolar-capillary barrier. Within 30 minutes 28.3% (controls, given normal rabbit serum: 0.7%) of iv 131I-albumin, and 0.5% (controls 0.02%) of iv surfactant phospholipid tracer were recovered in bronchoalveolar lavage. Furthermore, 57% (controls 32%) of the endotracheally administered surfactant phospholipid became associated with lung tissue and only less than 0.5% left the lung. The distribution of proteins and phospholipids between the in vivo small volume bronchoalveolar lavages and the ex vivo bronchoalveolar lavages were dissimilar: 84% (controls 20%) of intravenously injected, lavageable 131I-albumin and 23% (controls 18%) of total lavageable phospholipid were recovered in the in vivo small volume bronchoalveolar lavages. ALS also decreased lavageable surfactant phospholipid by 41%. After ALS the minimum surface tension increased. The supernatant of the lavage increased the minimum surface tension of normal surfactant. In addition, the sediment fraction of the lavage had slow surface adsorption, and a marked reduction in 35,000 and 10,000 MW peptides. Exogenous surfactant ameliorated the ALS-induced respiratory failure. We propose that inhibition, altered intrapulmonary distribution, and dissociation of protein and phospholipid components of surfactant are important in early pathogenesis of acute respiratory failure.     

Ultrastructural changes of venous autologous bypass grafts in rabbits: Correlation of patency and development

Summary Electron microscopic techniques were used to correlate the patency of venous autografts in rabbits with ultrastructural changes within a time range from 5 days to 6 months p.o. Early degenerative changes of the grafts include endothelial desquamation followed by fibrin deposition or platelet adhesion, mural edema and extensive medial and adventitial degeneration. The regeneration of the grafts is due to an early adventitial vascularization (10 days p.o.), which enables the surviving smooth muscle cells and fibrocytes to proliferate and to develop an arterial-like vessel. The organization of the 6-month-old graft is comparable to the carotid artery of the animal, but shows, in contrast, many features of a muscular artery.

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Zusammenfassung Mit Hilfe elektronenmikroskopischer Methoden wurde versucht, die Funktionsfähigkeit autologer Venentransplantate mit ultrastrukturellen Veränderungen in einem Zeitraum von 5 Tagen bis 6 Monaten p. o. zu korrelieren. Frühe degenerative Veränderungen der Transplantate umfassen Endothelabschilferungen mit anschließender Fibrin- bzw. Plättchenauflagerung, murale Ödeme und ausgedehnte mediale und adventitielle Degenerationen. Die Regeneration der Transplantate wird ermöglicht durch eine frühe adventitielle Kapillarisierung (10 Tage p. o.), die die überlebenden glatten Muskelzellen und Fibrozyten in die Lage versetzt, zu proliferieren und ein arterienähnliches Gefäß zu entwickeln. Der Aufbau der 6 Monate alten Vene ist vergleichbar mit der Arteria carotis communis der Tiere, zeigt aber im Gegensatz dazu überwiegend Merkmale einer Arterie vom muskulären Typ.

     

Fertility, pregnancy and the management of myeloproliferative disorders

The management of pregnant patients with chronic myeloproliferative disorders (MPD) is a difficult problem. Patients with essential thrombocythaemia (ET), and, less frequently, those with chronic myeloid leukaemia (CML) or polycythaemia vera (PV), present at a childbearing age. Pregnancy itself does not appear to affect adversely the natural course and prognosis of the MPD. However, fertility might be reduced, and an adverse outcome of pregnancy due to thrombotic or bleeding complications is a matter of concern. It ET, first-trimester abortion is the most frequent complication but increased perinatal mortality and premature delivery are also observed. Placental infarction due to thrombosis seems to be the most consistent event. Maternal thrombotic or haemorrhagic complications are rare but are more common than seen in normal pregnancy. The outcome of pregnancy seems to be positively influenced by aspirin, at least in some cases. The value of cytoreduction and/or heparin prophylaxis has not been established but may have a role in selected cases. In CML, the potential adverse effects of hyperleukocytosis, and sometimes thrombocytosis, generally make myelosuppressive treatment essential. In PV, the number of reported pregnancies is low. Maintaining the PCV below 0.45 is of the utmost importance relating to the outcome of pregnancy. Although cytoreductive drugs should generally be avoided, if possible, until at least after the first trimester of pregnancy, interferon-alpha seems to be the drug of choice when myelosuppression is indicated. In summary, the available information about pregnancy occurring during the course of an MPD indicates that successful management of pregnancy is possible. However, optimal management of these patients is poorly defined and agreed protocols are not available. In view of these problems, it is timely to consider the establishment of a national or European registry to monitor prospectively the management offered to pregnant women found to have an MPD.     

Prevention of recurrence after successful gallstone dissolution

Gallstone recurrence is a major problem in the medical treatment of gallstones (treatment with UDCA/CDCA, ESWL, local MTBE lysis). The probability of gallstone recurrence is higher in subjects with multiple stones before dissolution treatment and in older subjects (greater than 50 years). The present knowledge on factors predictive of gallstone recurrence and the results of clinical trials for preventing recurrence are given. The different effects of diet and drugs on cholesterol saturation of bile, on nucleation of bile, on mucus production of gallbladder and on gallbladder contractility are discussed and recommendations for a rational approach for prevention of gallstone recurrence are given. Preventable risk factors for gallstone disease have to be eliminated. In general, continuous post-dissolution treatment seems not justified. Regular follow-up ultrasound examinations should be started to detect renewed of gallstones at an early stage.     

Spontaneous remission in adult acute myeloid leukemia in association with systemic bacterial infection—case report and review of the literature

Spontaneous remission of acute myeloid leukemia in the adult is a rare event. We report on a 31-year-old male patient suffering from acute myeloid leukemia (AML) M5a according to the French-American-British (FAB) classification with biphenotypic features in flow cytometric examination and severe bacterial infection with group G streptococci at the time of diagnosis. Because of sepsis and stable clinical conditions, chemotherapy was delayed and antibiotics were administered intravenously. Within 6 weeks a spontaneous remission of AML occurred. Remission lasted for about 2 months. At the time of relapse, a change in phenotype of the leukemic blasts with a loss of B-lymphoid markers could be demonstrated by flow cytometry. The patient was treated with an induction therapy according to the multicentric German AMLCG 2000 schedule. To our knowledge, this is the first report of a spontaneous remission in an AML FAB M5a associated with coexpression of myeloid- and lymphoid-associated antigens on the leukemic blasts. Possible mechanisms of this phenomenon are discussed with a review of the literature.