Preserved brain functional plasticity after upper limb task-oriented rehabilitation in progressive multiple sclerosis.

BACKGROUND AND PURPOSE: Limited research has been dedicated to upper limb (UL) rehabilitation in progressive multiple sclerosis (PMS). The objective in this pilot study was to investigate the effect of task-oriented UL rehabilitation in PMS and to perform explorative analyses of the magnetic resonance imaging (MRI) correlates of changes in motor performance. METHODS: Twenty-six PMS patients with mild UL impairment were prospectively enrolled and randomized into two groups: an active treatment group (ATG, n = 13) and a passive treatment group (PTG, n = 13). At baseline and after training, patients underwent MRI scans with structural and functional imaging and were evaluated with the action research arm test, the nine-hole peg test, the ABILHAND scale and the modified fatigue impact scale (MFIS). Measures of motor finger performance were obtained by engineered glove measuring. RESULTS: After rehabilitation, the ATG improved in several finger motor tasks (0.001 ≤ P ≤ 0.03, 0.72 ≤ Cohen's d ≤ 1.22) and showed reduced MFIS scores compared with the PTG (P = 0.03). The ATG showed increased functional connectivity within the cerebellar and thalamic resting state networks compared with the PTG (P < 0.05). Correlations were found between several measures of motor improvement and thalamic and sensorimotor networks (0.87 ≤ r ≤ 0.93, 0.001 ≤ P ≤ 0.03). No changes in cerebral volumes and diffusion tensor imaging derived measures were detected. CONCLUSIONS: Progressive multiple sclerosis patients with mild UL dysfunction benefit from task-oriented UL rehabilitation, which seems to be more efficient than simple passive mobilization. Despite a high burden of disability and brain damage, functional adaptive capacities seem to be preserved, thus providing a rationale for the use of rehabilitative treatments in late PMS.

Aggressive multiple sclerosis: a single-centre, real-world treatment experience with autologous haematopoietic stem cell transplantation and alemtuzumab.

BACKGROUND AND PURPOSE: The best therapeutic approach for aggressive relapsing-remitting multiple sclerosis remains unknown. The objective was to compare the efficacy and safety of autologous haematopoietic stem cell transplantation (aHSCT) and alemtuzumab in aggressive relapsing-remitting multiple sclerosis. METHODS: The time to first relapse, time to confirmed disability worsening, time to first evidence of magnetic resonance imaging (MRI) activity and time to first evidence of disease activity were compared between the two treatment groups. Secondary outcomes included the 12, 24 and 36 month annualized relapse rate (ARR) and the 6-month confirmed Expanded Disability Status Scale (EDSS) changes at months 12 and 24. RESULTS: Fifty-seven patients treated with aHSCT (n = 25) or alemtuzumab (n = 32) were included. At baseline, aHSCT patients had a higher EDSS (median score 6 vs. 3; P < 0.001), higher ARR (mean ARR 3.2 vs. 1.7; P = 0.001) and a higher number of baseline T1 gadolinium-enhancing lesions on MRI (mean number 15.5 vs. 1.6; P < 0.001). NEDA-3 (no evidence of disease activity) status was more frequently achieved in aHSCT-treated patients than in alemtuzumab-treated patients [75% vs. 56% of patients at the end of the observation period; hazard ratio (HR) 0.27, 95% confidence interval (CI) 0.08-0.84; P = 0.023]. aHSCT significantly reduced the risk of relapse (relapse-free survival 84% vs. 69%; HR 0.13, 95% CI 0.02-0.63; P = 0.012) and MRI activity (MRI-activity-free survival 85% vs. 59%; HR 0.13, 95% CI 0.03-0.59; P = 0.009). The ARR at 36 months was significantly lower in the aHSCT group (0.05 vs. 0.35, P = 0.02). A significant effect of aHSCT in promoting EDSS improvement compared with alemtuzumab was noted (P = 0.035). CONCLUSIONS: Alemtuzumab and aHSCT are effective treatment choices for aggressive multiple sclerosis. aHSCT seems to be superior to alemtuzumab in inducing complete disease control and in promoting short-term disability improvement.

Fronto-temporal vulnerability to disconnection in paediatric moderate and severe traumatic brain injury.

BACKGROUND: In patients with moderate and severe paediatric traumatic brain injury (TBI), we investigated the presence and severity of white matter (WM) tract damage, cortical lobar and deep grey matter (GM) atrophies, their interplay and their correlation with outcome rating scales. METHODS: Diffusion tensor (DT) and 3D T1-weighted MRI scans were obtained from 22 TBI children (13 boys; mean age at insult = 11.6 years; 72.7% in chronic condition) and 31 age-matched healthy children. Patients were tested with outcome rating scales and the Wechsler Intelligence Scale for Children (WISC). DT MRI indices were obtained from several supra- and infra-tentorial WM tracts. Cortical lobar and deep GM volumes were derived. Comparisons between patients and controls, and between patients in acute (<6 months from the event) vs. chronic (≥6 months) condition were performed. RESULTS: Patients showed a widespread pattern of decreased WM FA and GM atrophy. Compared to acute, chronic patients showed severer atrophy in the right frontal lobe and reduced FA in the left inferior longitudinal fasciculus and corpus callosum (CC). Decreased axial diffusivity was observed in acute patients versus controls in the inferior fronto-occipital fasciculus and CC. Chronic patients showed increased axial diffusivity in the same structures. Uncinate fasciculus DT MRI abnormalities correlated with atrophy in the frontal and temporal lobes. Hippocampal atrophy correlated with reduced WISC scores, whereas putamen atrophy correlated with lower functional independence measure scores. CONCLUSIONS: The study isolated a distributed fronto-temporal network of structures particularly vulnerable to axonal damage and atrophy that may contribute to cognitive deficits following TBI.

Personalizing ocrelizumab treatment in Multiple Sclerosis: What can we learn from Sars-Cov2 pandemic?

During SARS-CoV-2 pandemic, we adopted a personalized delayed protocol for ocrelizumab infusions in Relapsing Remitting Multiple Sclerosis (RRMS) patients according to the national recommendations. Out of the 83 RRMS patients whose infusion was scheduled between March and December 2020, 56 patients experienced a delay in treatment based on MS severity and SARS-CoV2 infection risk profile. In most cases, the immunophenotype was performed monthly to guide re-infusions. Specifically, B CD19 + cells repopulation rate was monitored. Mean infusion delay was 103,1 [SD 40,6] days, and none of the patients presented relapses or active disease at MRI at the end of the observation period. Treatment naïve status and the interval between immunophenotyping and the last ocrelizumab infusion were predictors of earlier B CD19 + cells repopulation. Two patients contracted SARS-CoV2 with complete recovery. Definitive data about Sars-Cov2 vaccine efficacy in patients treated with ocrelizumab are still lacking. Our findings suggest that a personalized treatment with a delayed infusion schedule does not compromise ocrelizumab short-term efficacy and may help to lengthen the therapeutic window for an effective response to SARS-CoV2 vaccine.

A phospholipase A2 with anticoagulant activity. II. Inhibition of the phospholiped activity in coagulation.

An anticoagulant factor with phospholipase A2 activity has been isolated from Vipera berus venom. Phospholipase activity was studied on platelet phospholipid and on brain cephalin. The venom factor showed a potent anticoagulant activity: 1 mug impaired the clotting of 1 ml of citrated recalcified platelet-poor plasma. The anticoagulant inhibited clotting by antagonism to phospholipid. The antagonism constant (Kan = 6.8-10(-9) M) demonstrated the high affinity of the inhibitor for phospholipid. As with other phospholipases A2, the venom factor was thermoresistant but very sensitive to photo-oxidation. Both activities (anticoagulant activity and phospholipase activity) were not markedly dissociated by either denaturation or neutralization processes. Slightly different curves of photo-oxidative inactivation of both activities suggested the presence, on the molecule, of two very close sites responsible for phospholipase and anticoagulant activities. The inhibitor effect on coagulation was independent of the hydrolysis process. In fact, lysoderivatives and fatty acids, resulting from complete hydrolysis with the venom factor, were as active as the native phospholipids. Moreover phospholipase A2 from other viperidae venom, which did not have anticoagulant activity, produced similarly active lysoderivatives. This showed that the cleavage of the beta-acyl bond does not interfere with the activity of phospholipid. A possible mechanism of clotting inhibition by the venom factor was proposed. Owing to its high affinity for phospholipid, the inhibitor would complex phospholipid at its protein binding site impairing the normal arrangement of coagulation protein factors and, consequently, their activation. The positive charges of the inhibitor (pI = 9.2) could bind with phosphoryl or carboxyl groups of phospholipid, making them unavailable for protein binding. The complex formation involves a loss of dissociating capacity of the enzyme towards its substrate. This required an additional interaction of the inhibitor with a coagulation protein factor. The inhibitor could be removed from the complex by specific antibodies, permitting recovery of normal phospholipid-protein interaction. The role of calcium in the complex has not yet been elucidated. This venom factor affords a useful tool for investigating the phospholipid-clotting protein interaction.

A phospholipase A2 with anticoagulant activity. I. Isolation from Vipera berus venom and properties.

An anticoagulant protein has been isolated by DEAE cellulose chromatography and gel filtration from the venom of the Vipera berus orientale (Eastern Europe). Purification has been completed by elution on carboxymethyl cellulose with continuous gradient at constant pH. The inhibitor of coagulation was separated from the other venom enzymes, e.g. procoagulant, fibrinogenolytic, aminoesterase and amino acid oxidase activities. It was also separated from other phospholipase components which were not related to the anticoagulant property. The inhibitor appeared as a simgle polypeptidic chain protein, formed by 119 amino acid residues, with a molecular weight of 13400 and an isoelectric point of 9.2. At low saline molarity, a monomer-trimer transition of this protein was observed. Both forms had the same amino acid composition. There were six disulfide bridges without free SH groups per phospholipase molecule. Deprived of any proteolytic activity, the clotting inhibitor displayed a high phospholipase activity in the presence of calcium. Activity did no appear with EDTA buffer deprived of cation. Finely dispersed micellar suspensions were found suitable for obtaining the highest phospholipase activity. High sodium cholate concentration or methanol/chloroform/ether solvent were effective without loss of enzymatic activity. As characteristis of phospholipase A2 (EC 3.1.1.4), the degradation products identified on thin-layer chromatography induced hemolysis of human erythrocytes. The apparent Km value 1.25 - 10(-3) M was determined on phosphatidylcholine isolated from ovolecithin. This purified berus inhibitor would be of value for investigating the involvement of phospholipids in the clotting mechanism.

Effects of conditioned medium from bone marrow of normal and Ara-C-treated mice on hemoglobin synthesis.

Differentiation of CFUs toward erythropoiesis has been demonstrated in mice treated with a single dose of Ara-C, and this preferential differentiation was shown to be under the influence of diffusible factors. The aim of the work reported here was to determine whether these factors might include erythropoietin (Ep). This possibility was explored by testing the effect of the Ara-C-induced factor(s) on hemoglobin synthesis, and the effects of anti-mouse Ep on the activity of Ara-C-induced factors. When the late erythropoiesis stage of fetal liver cells was stimulated by bone-marrow-conditioned medium, no significant difference was observed between the effects of conditioned media obtained from normal versus Ara-C-treated bone marrow cells. Bone-marrow-conditioned medium induced a dose-dependent effect on hemoglobin synthesis by fetal liver cells (or adult bone marrow cells); the resulting curve was not parallel to the log-dose-response curve of purified mouse Ep. Anti-mouse Ep inhibited the activity of mouse Ep in fetal erythroblast cultures, but did not affect the stimulatory activity of conditioned media. Below the plateau doses no cumulative erythropoietic effect was observed in fetal erythroblast cultures when conditioned medium was added to Ep. Thus the present data suggest that the effect of bone-marrow-conditioned medium results from at least two independent factors: the first one active on CFUs differentiation towards erythropoiesis, and the second one active at a later stage of erythroid maturation. These factors can be considered to be molecules with an immunogenic structure unrelated to that of Ep.

Interactions between human plasma proteins and heparin-poly(methyl methacrylate) copolymer.

A solid Heparin-PMMA copolymer has been synthetized by a radical polymerization of methyl methacrylate from oxidative reaction initiated by Ce4+ ions in the presence of heparin. Covalently linked heparin was 10% of copolymer weight. The antithrombin activity of the copolymer corresponded to 1% of grafted heparin. PMMA sequence of the copolymer played the leading role in fibrinogen, immunoglobulins, transferrin and albumin adsorption. These proteins adsorbed on the copolymer, showed different competitive desorption pattern in the presence of whole plasma: fibrinogen presented the highest degree of affinity for the copolymer. The heparin part of the copolymer was responsible for antithrombin III adsorption and for decrease of factor V activity. Active antithrombin III was eluted. An inactivation of factor V in plasma was observed using high concentrations of soluble heparin. This result suggested that copolymer heparin chains, even devoid of antithrombin activity were involved in this inactivation. With Heparin-PMMA copolymer, plasma clotting pro-enzymes behaved differently than on heparin-sepharose copolymer:disappearance of factor XI activity, decrease in prekallikrein activity and activation of factor IX were observed. PMMA sequences were responsible for factor IX activation.

Morphologic spectrum of primary restrictive cardiomyopathy.

A restrictive hemodynamic profile with left ventricular (LV) end-diastolic volume < 100 ml/m2 and LV end-diastolic pressure > 18 mm Hg, in the absence of endomyocardial, pericardial, and specific cardiomyopathy, is a peculiar feature of primary restrictive cardiomyopathy. From 1985 to 1994, 7 hearts of patients who met the above hemodynamic criteria and underwent endomyocardial biopsy because of heart failure, were studied through gross (5 cardiectomies and 2 autopsies), histologic, and electron microscopic investigations. Ages ranged from 9 to 48 years (mean age 29 +/- 13). Four patients (57%) had a positive family history: 2 for hypertrophic and 2 for restrictive cardiomyopathy. Three patterns were identified in the 7 hearts: (1) pure restrictive form in 4 cases with mass/volume ratio 1.2 +/- 0.5 g/ml, ejection fraction 58 +/- 5%, LV end-diastolic volume 67.5 +/- 12.6 ml/m2, LV end-diastolic pressure 26.7 +/- 3.5 mm Hg; (2) hypertrophic-restrictive form in 2 cases with mass/volume ratio 1.5 +/- 0.07 g/ml, ejection fraction 62 +/- 1%, LV end-diastolic volume 69 +/- 10 ml/m2, LV end-diastolic pressure 30 +/- 7 mm Hg; and (3) mildly dilated restrictive form in 1 case with mass/volume ratio 0.9 g/ml, ejection fraction 25%, LV end-diastolic volume 98 ml/m2, LV end-diastolic pressure 40 mm Hg. Histology and electron microscopy disclosed myocardial and myofibrillar disarray and endoperimysial interstitial fibrosis in each pattern. The familial forms suggest the presence of a genetic abnormality. Primary restrictive cardiomyopathy may present with or without hypertrophy and shares similar microscopic pictures with hypertrophic cardiomyopathy. The 2 entities may represent a different phenotypic expression of the same genetic disease.

Effects of iloprost (ZK 36374) on glutathione status during ischaemia and reperfusion of rabbit isolated hearts.

1. Reperfusion of rabbit isolated hearts after 60 min of ischaemia resulted in poor recovery of mechanical function, release of creatine phosphokinase (CPK) and of reduced (GSH) and oxidized (GSSG) glutathione, reduction of mitochondrial superoxide dismutase (Mn SOD) activity and of tissue GSH/GSSG ratio with a shift of cellular thiol redox state toward oxidation, suggesting the occurrence of oxidative stress. 2. Pretreatment of the isolated heart with the stable prostacyclin analogue (iloprost) at 27 or 270 nM, but not at 2.7 nM, improved the functional recovery of the myocardium, reduced CPK, GSH and GSSG release, maintained Mn SOD activity and attenuated the occurrence of oxidative stress. 3. This effect of iloprost cannot be explained by a decreased demand or an enhanced delivery of oxygen during ischaemia or by a direct effect on glutathione peroxidase and reductase activity.

Donor shortage in heart transplantation. Is extension of donor age limits justified?

Chronic shortage of donor organs for heart transplantation led us to extend donor age limits. To verify the effectiveness of such a policy we have compared the results of heart transplantation in 45 patients with donors more than 40 years of age (group 1) with those of 72 patients older than 50 years of age who had heart transplantation with younger donors (group 2) between November 1985 and December 1992. The two groups were comparable in terms of mean recipient age, recipient and donor sex, and indication for heart transplantation. Mean donor age was 46 +/- 4 years (range 41 to 59 years) in group 1 and 23 +/- 7 years (range 8 to 39 years) in group 2 (p < 0.001). In group 1 cerebrovascular accidents were more common as the cause of donor death (60% versus 16%, p = 0.001), and no difference was found in ischemic time (144 +/- 47 minutes versus 140 +/- 48 minutes, p = not significant). There were 6 early (< 30 days) deaths in group 1 (13%) and 10 in group 2 (14%; p = not significant). Fatal acute graft failure was more prevalent, but not significantly so, in group 1 (10% versus 5.5%, p = not significant). Mean follow-up was 29 +/- 20 months (range 3 to 78 months) in group 1 and 30 +/- 20 months (range 3 to 80 months) in group 2 (p = not significant). At 5 years actuarial survival was 80% +/- 6% in both groups with comparable graft performance at echocardiographic and hemodynamic control studies. A significant difference was found in freedom from any type of coronary artery abnormality between group 1 (49% +/- 13%) and group 2 (77% +/- 8%) at 5 years (p < 0.05); however, freedom from coronary stenotic lesions only was similar. Major conduction disturbances have occurred more frequently in patients of group 1 (37% versus 12%; p = 0.003) without any difference in the need for permanent pacing. Donors older than 40 years of age can be accepted for heart transplantation with early and long-term results comparable with those obtained with younger donors. The impact of a higher incidence of coronary abnormalities on late performance of older grafts must be assessed at longer follow-up. Our results indicate that, because of the current organ shortage, extension of donor age limits is justified, even up to the sixth decade of life in selected cases.

Polycythemia in chronic obstructive pulmonary disease. A study of serum and urine erythropoietin and medullary erythroid progenitors.

In order to investigate the mechanism of polycythemia in chronic obstructive pulmonary disease (COPD), serum and urinary levels of erythropoietin and medullary erythroid progenitors were studied in 21 patients; nine were nonpolycythemic (hematocrit, 39 +/- 4 percent; red blood cell [RBC] mass, 28 +/- 5 ml/kg; forced expiratory volume in one second [FEV1], 0.6 +/- 0.1 L), and 12 patients were polycythemic (hematocrit, 52 +/- 7 percent; RBC mass, 46 +/- 7 ml/kg; FEV1, 0.9 +/- 0.3 L). Hypoxia was severe in both groups, with mean arterial oxygen pressure of 47 mm Hg. The following parameters of tissue oxygenation were not significantly different between the two groups: arterial and mixed-venous oxygen saturations; cardiac output; oxygen utilization coefficient; 2, 3-diphosphoglycerate, and carboxyhemoglobin level. The level of erythropoietin was measured by bioassay in vitro. The level was increased in the serum of 85 percent (18) and in the urine of 38 percent (8) of the patients. There was no significant difference between the nonpolycythemic and polycythemic groups. Without exogenous erythropoietin, none of the subjects showed spontaneous colonies of erythroid progenitors. The addition of one unit of erythropoietin induced a similar normal proliferation of erythroid progenitors in both groups. The absence of adaptative polycythemia in the nonpolycythemic group with severe hypoxia was seemingly related neither to a quantitative deficit of erythropoietin nor to a lack of sensitivity of erythroid progenitors to its action.

Global and regional left ventricular function in heart transplant patients: an angiographic follow-up study.

We studied the global and regional left ventricular function, its determinants and its modification with time, in orthotopic heart transplant recipients. We reviewed the left ventricular cineangiography performed 1 (50 patients), 2 (33 patients), 3 (18 patients), and 4 (seven patients) years after operation. Regional wall motion was quantitatively evaluated by the area method. All patients had angiographically normal coronary arteries and no evidence of acute rejection at the time of the study. One year after heart transplantation, cardiac index and left ventricular ejection fraction were mildly but significantly lower than normal. Cardiac index was more than 2.5 L/min/m2 in all but one patient, and ejection fraction was more than 50% in all patients. Only previous acute cardiac rejection necessitating therapy and arterial hypertension showed some influence on the left ventricular function. Two years after operation, the left ventricular end-diastolic volume was increased, and left ventricular mass-volume ratio decreased compared with year 1. Three years after operation, an increase of left ventricular end-diastolic pressure and of left ventricular ejection fraction was also evident. Four years after operation, the heart rate was higher, compared with previous years. Even if the changes in the parameters of left ventricular function were significant, they were small in terms of absolute value. Regional hypokinesia was detected 1 year after heart transplantation in eight patients, involving one segment in six patients and two segments in two patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Discordance between pre and post cardiac transplant diagnosis: implications for pre- and postoperative decision making.

A correct clinical diagnosis in end-stage patients undergoing cardiac transplantation may have important prognostic and therapeutic implications. A retrospective clinico-pathologic study was carried out in 257 patients who had undergone cardiac transplantation at the University of Padua. A discrepancy between clinical and pathological diagnosis was found in 20 cases (8%). Among 126 patients with the clinical diagnosis of dilated cardiomyopathy, seven were found eventually to have ischemic heart disease (IHD), five myocarditis, one arrhythmogenic right ventricular cardiomyopathy (ARVC), and one non-compacted myocardium. Among the 87 patients with clinical diagnosis of IHD, three turned out to be dilated cardiomyopathy and one granulomatous myocarditis. Among the 10 patients with the clinical diagnosis of hypertrophic-restrictive cardiomyopathy, one had ARVC and one had cardiac fibroma. Altogether, only 24.5% underwent endomyocardial biopsy (EMB) and 75% coronary angiography before transplantation. Missed diagnosis of myocarditis occurred in patients in whom EMB was not carried out. EMB and coronary angiography might be indicated routinely in patients with apparent dilated cardiomyopathy, before proceeding to cardiectomy.

Oxygen free radical-mediated heart injury in animal models and during bypass surgery in humans. Effects of alpha-tocopherol.

There is evidence that oxygen free radicals play a role in myocardial ischemic and reperfusion injury. We investigated the effect of ischemia and reperfusion on glutathione status. Reperfusion after prolonged ischemia (60 min) induced an important release of reduced (GSH) and oxidized (GSSG) glutathione, concomitant with an increase of tissue GSSG and no recovery of mechanical function, indicating that reperfusion results in oxidative stress. These alterations are associated with tissue and mitochondrial calcium accumulation, loss of mitochondrial function, and membrane damage. We also determined the arteriocoronary sinus difference for GSH and GSSG of 16 CAD patients undergoing coronary artery bypass. Patients were divided in two groups according to the length of clamping period: 25 +/- 2 min (group 1), and 55 +/- 6 min (group 2). In group 1, reperfusion resulted in a transient release of GSH, GSSG, CPK, and lactate, with return to preclamping values in 10 minutes. In group 2, reperfusion determined a sustained and pronounced release of GSH, GSSG, CPK, and lactate during declamping, suggesting the occurrence of an oxidative stress. Using an in vitro model, administration of alpha-tocopherol bound with albumin showed protection of mitochondrial function, improved recovery of contraction, and reduced oxidative stress during reperfusion.

Clinical results of steroid-free induction immunosuppression after heart transplantation.

Between January 1987 and September 1991, 112 operative survivors of heart transplantation were initially immunosuppressed with cyclosporin A and azathioprine without prednisone. Eighty-eight patients (79%) remained on a regimen of double therapy for a mean follow-up of 25 +/- 15 months (range, 1 to 54 months), whereas 24 patients (21%) had oral prednisone, 5 mg/day, added to maintenance therapy for persistent or repeated rejection. There were 5 early deaths (4%) because of acute rejection (4 patients) or infection (1 patient). Only 1 patient died late after heart transplantation of chronic rejection. Actuarial survival was 95% +/- 2% and 94% +/- 3% at 12 and 48 months, respectively. Mean rate of acute rejection was 1.7 +/- 1.0 episodes per patient, with a 5% +/- 2% freedom from rejection at 48 months. Ten patients (9%) required in-hospital treatment for infection; the actuarial freedom from infectious episodes was 85% +/- 4% at 48 months. Actuarial freedom from hypertension was 43% +/- 7% at 48 months. At annual catheterization, mean left ventricular ejection fraction was 0.64 +/- 0.08 and 0.62 +/- 0.05 at 1 year and 4 years, respectively, with evidence of coronary lesions in 9 patients (8%). In conclusion, steroid-free immunosuppression after heart transplantation is associated with a high incidence of acute rejection. However, the excellent medium-term survival and the low incidence of both infection and chronic rejection seem to justify a wider use of such treatment.

Pachydermoperiostosis with gastric hypertrophy, anemia, and increased serum bone Gla-protein levels.

We evaluated a patient in whom pachydermoperiostosis occurred in conjunction with anemia and gastric hypertrophy. The mechanism of the anemia appears multifactorial because, besides a myelofibrosis, a serum inhibitor of the late stage of erythropoiesis was detected. The elevated serum bone Gla-protein (osteocalcin) favors the hypothesis that primary hypertrophic osteoarthropathy represents an imbalance between increased osteoblastic bone formation and normal bone resorption.

Cardiomyopathy: a necessary revision of the WHO classification.

The classification of myocardial disease proposed by the WHO/ISFC task force in 1980 distinguishes specific heart muscle diseases from myocardial diseases of unknown origin, termed cardiomyopathies, and differentiated into the dilated, hypertrophic and restrictive forms. This last group includes endomyocardiofibrosis and fibroblastic parietal endocarditis. In more recent years, two new forms of heart muscle disease have been recognized: so-called "primary" restrictive cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy. Primary restrictive cardiomyopathy is characterized anatomically by normally sized, non-hypertrophic ventricles with dilated atria, and functionally by impaired diastolic compliance due to myocardial stiffness. The clinical picture is that of chronic congestive heart failure; histology shows interstitial fibrosis and myocardial disarray, but not hypereosinophilia. In arrhythmogenic right ventricular cardiomyopathy, the myocardium of the right ventricular free wall is substituted by fibrous and/or adipose tissue, which results in regional dynamic alterations and ominous ventricular arrhythmias. The left ventricle is usually spared. Both forms should be classified as heart muscle diseases of unknown origin, and kept clearly distinct from the other cardiomyopathies listed in the WHO classification.

Angiographic presentation of coronary artery spasm in heart transplant recipients.

We describe the angiographic characteristics of coronary artery spasm observed in 12 out of 247 (4.9%) patients who underwent 808 coronary angiographies after heart transplantation. Coronary artery spasm was diagnosed when localized and reversible narrowing of the coronary lumen was identified. After coronary artery spasm identification all patients were followed-up clinically for a mean period of 5.1 years. Coronary artery spasm was documented 1-3 years after heart transplant. Coronary artery spasm affected 1 main coronary artery in 10 patients and 2 in 2 patients; in 3 patients 1 or more secondary branches were also affected. The right coronary artery was affected by coronary artery spasm in 8 patients and the anterior descending coronary artery in 6 patients. In 6 patients coronary artery spasm was mechanically induced by the catheter tip. The degree of luminal narrowing due to coronary artery spasm ranged from mild to almost complete occlusion. Coronary artery spasm appeared as a single tubular smooth and concentric stenosis in 8 patients, was discrete in 2 patients and multiple on the same vessel in 2 patients. In 1 patient coronary artery spasm was erroneously interpreted as an organic lesion and percutaneous transluminal coronary angioplasty was planned. During follow-up 3 patients out of 4 who had shown multiple coronary artery spasm died and 2 patients developed critical organic stenosis. In conclusion coronary artery spasm after heart transplant is less rare than commonly believed. Although it usually has a peculiar appearance, it can be misinterpreted as an organic lesion. Multiple coronary artery spasm appears to carry a poor prognosis.