Iatrogenic cyanosis and clubbing: 25 years of chronic hypoxia after the repair of an atrial septal defect

A case of sinus venosus atrial septal defect repair of the inferior vena caval type with an unintentional diversion of the inferior vena caval blood to the left atrium is reported. Long-standing, anatomical, right-to-left shunting with cyanosis and hypoxia are associated with systemic and cerebrovascular complications. Cardiac risks depend on the presence or absence of pulmonary hypertension, the associated hematological abnormalities and the degree of anatomical, right-to-left shunting. Cardiac magnetic resonance imaging clarified the etiology of the unexplained cyanosis and delineated the surgical anatomy.     

Subepicardial aneurysm with impending cardiac rupture: a case of antemortem diagnosis and review of the literature

Subepicardial aneurysm is a rare, life-threatening complication of acute myocardial infarction. Relatively few cases are diagnosed early enough to allow for surgical intervention. Features of this unique aneurysm include abrupt interruption of the myocardium, a narrow neck, and a propensity for progressing to sudden transmural rupture. Literature review reveals only 20 reported cases, several of which were identified postmortem. Since the myocardial burrow may progress to pseudoaneurysm or frank rupture prior to the diagnosis being made, the true incidence is unknown. Invariably, the condition develops as a result of a myocardial rent occurring during the weeks to months following acute infarction, and it generally occurs within an area of thinned, infarcted myocardium. Successful surgical repair has been reported in several cases and is the only therapy shown to prevent progression to frank rupture. Antemortem diagnosis has been reported with transthoracic echocardiography, transesophageal echocardiography, cardiac catheterization, and magnetic resonance imaging. Unfortunately, each of these imaging techniques appears to be limited by either inadequate sensitivity or slow acquisition. There remains no standard of reference among available diagnostic modalities. Rapidly obtained, contrast-enhanced computed tomography in the proper clinical setting may improve the ability of clinicians to identify this condition during a window of therapeutic opportunity, allowing surgical intervention to prevent fatal cardiorrhexis. Subepicardial aneurysm should be included in the differential diagnosis for patients presenting with chest pain following acute myocardial infarction.     

Initial experience with the AbioCor implantable replacement heart system

OBJECTIVE: We sought to evaluate the safety and efficacy of the first available totally implantable replacement heart (AbioCor Implantable Replacement Heart System) in the treatment of severe, irreversible biventricular heart failure in human patients. METHODS: Seven male adult patients with severe, irreversible biventricular failure (>70% thirty-day predicted mortality) who were not candidates for transplantation met all institutional review board study criteria and had placement of the AbioCor Implantable Replacement Heart. All were in cardiogenic shock despite maximal medical therapy, including inotropes and intra-aortic balloon pumps. Mean age was 66.7 +/- 10.4 years (range, 51-79 years). Four of 7 patients had prior operations. Six had ischemic and one had idiopathic cardiomyopathy. All had 3-dimensional computer-simulated implantation of the thoracic unit that predicted adequate fit. At the time of the operation, the internal transcutaneous energy transfer coil, battery, and controller were placed. Biventriculectomy was then performed, and the thoracic unit was placed in an orthotopic position and attached to the atrial cuffs and outflow conduits with quick-connects. The flow was adjusted to 4 to 8 L/min. Central venous and left atrial pressures were maintained at 5 to 15 mm Hg. The device is powered through transcutaneous energy transfer. An atrial flow-balancing chamber is used to adjust left/right balance. The balance chamber and transcutaneous energy transfer eliminate the need for percutaneous lines. RESULTS: There was one intraoperative death caused by coagulopathic bleeding and one early death caused by an aprotinin reaction. There have been multiple morbidities primarily related to preexisting illness severity: 5 patients had prolonged intubation, 2 had hepatic failure (resolved in 1), 4 had renal failure (resolved in 3), and 1 each had recurrent gastrointestinal bleeding, acute cholecystitis requiring laparotomy, respiratory failure that resolved after 3 days of extracorporeal membrane oxygenation, and malignant hyperthermia (resolved). There were 3 late deaths: one caused by multiple systems organ failure (postoperative day 56), one caused by a cerebrovascular accident (postoperative day 142), and one caused by retroperitoneal bleeding and resultant multiple systems organ failure (postoperative day 151). This latter patient was not able to tolerate anticoagulation (no anticoagulation or antiplatelet therapy alone for 80% of the first 60 days) and had a transient ischemic attack on postoperative day 61 and a cerebrovascular accident on postoperative day 130. At autopsy, blood pumps were clean. The 2 patients who had large cerebrovascular accidents had thrombus on the atrial cage struts. These struts have been removed for future implants. There has been no significant hemolysis or device-related infections. The balance chamber has allowed for left/right balance in all patients (left atrial pressure within 5 mm Hg of right atrial pressure). Three patients have taken multiple (>50) trips out of the hospital, and 2 have been discharged from the hospital. Total days on support with the AbioCor are 759. CONCLUSION: The initial clinical experience suggests that the AbioCor might be effective therapy in patients with advanced biventricular failure. There have been no significant device malfunctions. Two of these patients have been discharged from the hospital.     

The apoptotic effect of somatostatin analogue SMS 201-995 on human lymphocytes

The antiproliferative effect of a synthetic octapeptide, somatostatin analogue SMS 201-995 (SMS), and its capacity to bind were evaluated on human peripheral blood lymphocytes (PBL) activated by phytohemoagglutinin (PHA).We then addressed our work to investigate if SMS inhibits PHA activation of PBL by a cytostatic rather than a cytotoxic mechanism. Consequently, we studied the cell cycle distribution and the activation of caspase-3, measuring the presence of the cleavage product of poly(ADP-ribose) polymerases (PARP), and we evaluated the presence of apoptotic DNA by using a monoclonal antibody specific for the single-stranded regions of DNA. All our results indicate that SMS induces apoptosis in activated lymphocytes.     

Inhibitory activity of luteinizing hormone-releasing hormone on tumor growth and progression

Luteinizing hormone-releasing hormone (LHRH) is the key hormone in the control of reproductive functions. In recent years, it has become evident that LHRH might act as a growth modulatory factor in tumors of the reproductive system. We have shown that in prostate cancer cells LHRH is expressed, together with its receptors, to negatively regulate cell proliferation. In these cells, LHRH acts as an antimitogenic factor through the activation of the Gi-cAMP intracellular signaling pathway. More recently, we investigated whether an LHRH-based autocrine system might also be expressed in tumors that are not classically related to the reproductive tract, such as melanoma. Malignant melanoma is known to be characterized not only by a high proliferation rate, but also by an aggressive metastatic behavior. We have demonstrated that both LHRH and LHRH receptors are expressed in human melanoma cells (BLM and Me15392). Activation of LHRH receptors by means of a potent LHRH agonist (Zoladex) significantly inhibited cell proliferation. The LHRH agonist also reduced the ability of melanoma cells to invade a reconstituted basement membrane (Matrigel) and to migrate in response to a chemotactic stimulus. These data indicate that: (a) in prostate cancer cells the LHRH receptor is coupled to a Gi-cAMP signal transduction pathway; (b) LHRH and LHRH receptors are also expressed in tumors that are not classically related to the reproductive system, such as melanoma; in melanoma cells, LHRH might act as an inhibitory factor on both cell proliferation and metastatic behavior. It is suggested that, in melanoma, LHRH receptors might represent a diagnostic marker and a possible molecular target for new therapeutic approaches for this pathology.     

Short-term bridge to transplant using the BVS 5000 in a 22-kg child

The availability of pulsatile mechanical assist devices for bridge to transplant in pediatric patients is limited owing to the patients’ small sizes. Pulsatile devices offer potential advantages over nonpulsatile devices but the risk of hypertensive bleeding must be balanced against that of device thrombosis. We describe our experience using the BVS 5000 external pulsatile device in an 8-year old patient with a body surface area of 0.88 m².     

An ultrastructural morphometric analysis of the adenohypophysis of lactating rats

A morphometric analysis of the adenohypophysis (pars distalis) of lactating rats was carried out by a semi-automated method at the ultrastructural level. The cellular elements were identified by their ultrastructural morphology. The following values were considered for the morphometric study: numerical density of cells/mm3 of tissue and the percentage of parenchymal volume occupied by every cell type. Mammotropes (PRL cells) numbered 624 X 10(3)/mm3 and occupied 59.9% of the parenchymal volume (p.v.). Somatotropes (GH cells) numbered 206 X 10(3)/mm3 and occupied 15.0% of the p.v. Folliculo-stellate cells (FS cells) numbered 128 X 10(3)/mm3 and occupied 8.1% of the p.v. Gonadotropes (GN cells) numbered 47 X 10(3)/mm3 and occupied 6.0% of the p.v. Adrenocorticotropes (ACTH cells) numbered 45 X 10(3)/mm3 and occupied 3.8% of the p.v. Thyrotropes (TSH cells) numbered 36 X 10(3)/mm3 and occupied 3.4% of the p.v. PRL cells were characterized by aspects compatible with intense hormone production. GH cells did not show differences with those of nonlactating animals. Folliculo-stellate elements appeared hypertrophic with abundant cytoplasm, enlarged Golgi complex, and dilation of the follicular lumina. GN cells had abundant cytoplasm with a well-developed and dilated ergastoplasm, particularly in type II GN cells. ACTH cells did not show differences with those of nonlactating animals. TSH cells showed moderate nucleocytoplasmic activation. These fine structural morphometric findings are discussed in relation to other studies regarding nonlactating adenohypophysis and hormone changes during lactation.     

Growth-inhibitory activity of melatonin on human androgen-independent DU 145 prostate cancer cells

BACKGROUND: The pineal hormone melatonin has been shown to exert a direct oncostatic activity on neoplastic cells, particularly from breast cancer. In the present study, we evaluated the effects of melatonin on the proliferation and on the cell cycle distribution of human androgen-independent DU 145 prostate cancer cells. Experiments were also performed to gain insights into the possible mechanism of action of the hormone. METHODS: The effects of melatonin on DU 145 cell proliferation was analyzed by counting the cells by hemocytometer at the end of treatment. The effects of the pineal hormone on cell cycle distribution were evaluated by FACS analysis. RT-PCR studies were performed to detect Mel(1a) and Mel(1b) expression in DU 145 cells. The cellular localization of (125)I-melatonin binding sites was investigated by radioreceptor assay. A commercially available binding-protein assay kit was utilized to evaluate intracellular cAMP levels. RESULTS: Melatonin, in physiological doses, significantly inhibited DU 145 cell proliferation and induced cell cycle withdrawal by accumulating cells in G0/G1 phase. The mRNA for Mel(1a) receptors was found to be expressed in DU 145 cells; however, by radioreceptor assay, no binding sites for (125)I-melatonin could be detected in membrane preparations, suggesting that, in these cells, the level of translation of this mRNA is too low to possibly mediate the antiproliferative action of the hormone. In agreement with this hypothesis, melatonin did not affect forskolin-induced intracellular cAMP accumulation. Binding sites for (125)I-melatonin were found in nuclear extracts of DU 145 cells. CONCLUSIONS: Melatonin exerts a direct oncostatic activity on human androgen-independent prostate cancer cells, by affecting cell cycle progression. This activity seems to be mediated by nuclear, but not by membrane, receptors.     

Growth-inhibitory effects of luteinizing hormone-releasing hormone (LHRH) agonists on xenografts of the DU 145 human androgen-independent prostate cancer cell line in nude mice

Experiments have been performed to clarify whether LHRH agonists might decrease growth of hormone-unresponsive prostate cancer in vivo. Male nude mice were injected s.c. with the human androgen-independent prostate tumor DU 145 cells; osmotic minipumps releasing the LHRH agonist Zoladex (LHRH-A) for 14 days were simultaneously implanted under the skin. Treatment with LHRH-A induced a significant decrease in tumor growth up to the end of the treatment. In subsequent experiment, minipumps releasing LHRH-A were implanted in nude mice either 7 or 14 days after cell inoculation. When the treatment was started 7 days after inoculation of the cells, tumor growth was significantly decreased up to 28 days; thereafter, tumor volume remained lower than in controls, although not significantly. When LHRH-A was administered beginning 14 days after cell inoculation, tumor growth was not significantly affected at any time interval considered. LHRH-A did not appear to induce apoptosis in DU 145 cells, at least on the basis of the apoptotic index and immunohistochemical staining of the p53 protein. On the other hand, treatment with LHRH-A was accompanied by a significant decrease of the concentration of epidermal growth factor receptors in DU 145 prostate cancer specimens. Our results show that the LHRH agonist used significantly inhibits the growth of DU 145 androgen-independent prostate tumor xenografts in nude mice. Int. J. Cancer 76:506–511, 1998.© 1998 Wiley-Liss, Inc.