Valve-related complications with the Hancock I porcine bioprosthesis. A twelve- to fourteen-year follow-up study

Valve-related morbidity and mortality after heart valve replacement with the Hancock I porcine bioprosthesis has been retrospectively analyzed. From June 1974 through December 1976, 253 Hancock I bioprostheses (150 mitral and 103 aortic) were inserted in 220 selected patients who survived the operation and had follow-up until June 1989 (mean follow-up 13.5 years, with an accumulative follow-up of 2956.4 patient-years). One hundred seventeen patients had mitral valve replacement, 70 had aortic valve replacement, and 33 had combined mitral and aortic valve replacement. There were 27 thromboembolic events. The probability of being free from thromboembolism at 14 years was 81.0% +/- 7.4% for the mitral valve replacement group, 85.4% +/- 6.7% for the aortic group, and 67.1% +/- 18.4% for the mitral-aortic group. Fifteen episodes of prosthetic valve endocarditis occurred. There were 10 instances of nonstructural dysfunction (paravalvular leaks) in seven mitral valves (4.6%) and in three aortic valves (2.9%). One hundred twenty-two bioprostheses in 106 patients resulted in structural deterioration. The probability of freedom from structural deterioration at 14 years was 37.2% +/- 3.9% for the mitral group, 43.9% +/- 7.1% for the aortic group, and 30.1% +/- 8.9% for the mitral-aortic group. The logistic regression analysis between age at the time of operation and bioprosthetic life (structural deterioration-free period) demonstrates a linear regression curve (r = 0.53). There were 56 late deaths (27 patients died at reoperation). The actuarial survival rate (including hospital mortality) at 14 years was 57.2% +/- 5.4% for the entire series, with no statistically significant difference between groups. The probability of remaining free from valve-related morbidity and mortality at 14 years was 16.7% +/- 4.8% for the mitral group, 20.8% +/- 6.2% for the aortic group, and 14.0% +/- 7.0% for the mitral-aortic group. The long-term results of this series show that the clinical performance of the Hancock I porcine valve appears satisfactory during the first 6 years. The behavior of this bioprosthesis at 14 years' follow-up changes drastically, because only a minor group of patients is free from valve-related complications, justifying the restriction of its use for selected patients.     

Prenatal stroke suggested by intrauterine ultrasound and confirmed by magnetic resonance imaging.

Cerebral infarction is rare in premature newborns and is most commonly the result of arterial embolization from the placenta. A focal echodense area was identified on prenatal cranial ultrasonography (US) in a premature infant (34 weeks of gestation). After birth, cerebral infarction was confirmed by magnetic resonance imaging (MRI). The clinical findings, imaging findings and pathogenesis are discussed. New diagnostic methods such as MRI show to be a useful approach in the neonatal period facilitating recognition of cerebrovascular accidents also in low-birth-weight infants.     

Cloning and characterization of Ca(2+)-dependent and Ca(2+)-independent PKCs expressed in Aplysia sensory cells

We isolated cDNA clones from an Aplysia sensory-cell library encoding two isoforms of protein kinase C (PKC). Several isozyme-specific regions are conserved in the Aplysia kinases, notably the variable regions V5 in the Ca(2+)-dependent PKC (Apl I) and V1 in the Ca(2+)-independent PKC (Apl II). Neuronal proteins with the properties expected of these two isoforms can be identified with antibodies raised against peptides synthesized from the amino acid sequences deduced from the clones. Sacktor and Schwartz (1990) measured the proportion of kinase activity that can be translocated to membrane in Aplysia sensory neurons and ganglia by stimuli that produce the presynaptic facilitation underlying behavioral sensitization. Much less Apl I and Apl II are translocated, suggesting that still other isoforms of PKC exist in these cells.     

Regionally selective effects of NMDA receptor antagonists against ischemic brain damage in the gerbil

This study compared the ability of three N-methyl-D-aspartate (NMDA) receptor antagonists to prevent neuronal degeneration in an animal model of global cerebral ischemia. The model employed is characterized by damage to the striatum, hippocampus, and neocortex. Antagonists were administered to gerbils either before or after a 5-min bilateral carotid occlusion. The intraischemic rectal temperature was either maintained at 36-37 degrees C or allowed to fall passively to 28-32 degrees C. Antagonists and doses tested were 1 and 10 mg/kg of MK-801 (pre- or postischemia), 30 mg/kg of CGS 19755 preischemia, four 25 mg/kg doses of CGS 19755 administered between 0.5 and 6.5 h postischemia, and 40 mg/kg of MDL 27,266 (pre- or postischemia). All three NMDA receptor antagonists exhibited some degree of neuroprotective activity when the carotid occlusion was performed under normothermic conditions. Most of the treatments with antagonist markedly reduced striatal damage. CA1 hippocampal and neocortical pyramidal cells were spared by only three of the treatments, however, and the extent of neuroprotection varied widely from case to case. Toxic doses of antagonist were required to protect CA1 pyramidal cells from ischemic damage. Ischemic damage to hippocampal areas CA2-CA3a and CA4 appeared to be resistant to all of these treatments. Most CA1 pyramidal cells that were protected from degeneration by an NMDA receptor antagonist were histologically abnormal. The neuroprotective effects of MK-801 and intraischemic hypothermia appeared to be additive. MK-801 (10 mg/kg) consistently reduced the postischemic brain temperature, but only the magnitude of hypothermia produced soon after reperfusion correlated with its neuroprotective action. These results suggest that NMDA receptor antagonists are relatively poor neuroprotective agents against a moderately severe ischemic insult.     

Neuropeptide levels in the basal ganglia of aged common marmosets following prolonged treatment with MPTP

Summary Aged common marmosets were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 0.5–2.0 mg/kg/week i.p.) for 16 or 24 weeks, observed for a total of 30 weeks and then killed for measurement of biochemical pramaters in basal ganglia. The MPTP treatment induced a marked depletion in dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels in the caudate nucleus and putamen. In contrast, the concentrations of five neuropeptides: [Met⁵]-enkephalin, [Leu⁵]-enkephalin, cholecystokinin, substance P and neurotensin as measured by a combined HPLC/RIA method, remained unaltered in all basal ganglia regions examined. Enkephalin precursor levels, as reflected by cryptic [Met⁵]-enkephalin content, were increased in the putamen, but not in the caudate nucleus, as a consequence of MPTP administration. Cryptic [Leu⁵]-enkephalin content remained unchanged in the striatum of MPTP treated marmosets. Overall, these results suggest an increase in striatal [Met⁵]-enkephalin release following chronic MPTP treatment of aged marmosets. However, the chronic treatment of aged marmosets with MPTP does not reproduce the neuropeptide alterations characteristic of Parkinson's disease.     

Ticlopidine and clopidogrel (SR 25990C) selectively neutralize ADP inhibition of PGE1-activated platelet adenylate cyclase in rats and rabbits

Ticlopidine and its potent analogue, clopidogrel, are powerful inhibitors of ADP-induced platelet aggregation. In order to improve the understanding of this ADP-selectivity, we studied the effect of these compounds on PGE1-stimulated adenylate cyclase and on the inhibition of this enzyme by ADP, epinephrine and thrombin. Neither drug changed the basal cAMP levels nor the kinetics of cAMP accumulation upon PGE1-stimulation in rat or rabbit platelets, which excludes any direct effect on adenylate cyclase or on cyclic nucleotide phosphodiesterase. However, the drop in cAMP levels observed after addition of ADP to PGE1-stimulated control platelets was inhibited in platelets from treated animals. In contrast, the drop in cAMP levels produced by epinephrine was not prevented by either drug in rabbit platelets. In rat platelets, thrombin inhibited the PGE1-induced cAMP elevation but this effects seems to be entirely mediated by the released ADP. Under these conditions, it was not surprising to find that clopidogrel also potently inhibited that effect of thrombin on platelet adenylate cyclase. In conclusion, ticlopidine and clopidogrel selectively neutralize the ADP inhibition of PGE1-activated platelet adenylate cyclase in rats and rabbits.