Functional inhibition and release: unilateral tachistoscopic performance and stereoelectroencephalographic activity in a case with left limbic status epilepticus

During prolonged nonconvulsive unilateral left limbic status epilepticus, a natural model of functional hemispheric inhibition, we performed two tachistoscopic experiments, a lexical decision task associated with a RVF (left hemisphere) superiority and a facial matching task associated with a LVF (right hemisphere) superiority. We found that epileptic activity in the left hemisphere, especially rhythmic high-frequency "tonic" discharges, inhibited performance on the lexical task but not on the facial matching task. This suggests that only cognitive activity in the discharging hemisphere is inhibited. Strikingly, the best performance of the right hemisphere was obtained while the left hemisphere was most inhibited, suggesting a functional balance of inhibition and release.     

Cervical myelopathy in mucopolysaccharidosis type IV

We describe our experience with 8 Italian patients having mucopolysaccharidosis type IV, diagnosed between 1 and 10 years of life, who presented odontoid hypoplasia causing cervical myelopathy. We discuss the possibility of cranio-cervical stabilization in order to reduce the neurological complications.     

Adult height in girls with central precocious puberty treated with gonadotropin-releasing hormone analogues and growth hormone

GnRH analogues (GnRHa) represent the treatment of choice in central precocious puberty (CPP), because arresting pubertal development and reducing either growth velocity (GV) or bone maturation (BA) should improve adult height. However, in some patients, GV decrease is so remarkable that it impairs predicted adult height (PAH); and therefore, the addition of GH is suggested. Out of twenty subjects with idiopathic CPP (treated with GnRHa depot-triptorelin, at a dose of 100 microg/kg im every 21 days, for at least 2-3 yr), whose GV fall below the 25th percentile for chronological age, 10 received, in addition to GnRHa, GH at a dose of 0.3 mg/kg x week s.c., 6 days weekly, for 2-4 yr; and 10 matched for BA, chronological age, and duration of GnRHa treatment, who showed the same growth pattern but refused GH treatment, served to evaluate the efficacy of GH addition. No patient showed classical GH deficiency. Both groups discontinued treatment at a comparable BA (mean +/- SEM): 13.2 +/- 0.2 in GnRHa plus GH vs. 13.0 +/- 0.1 yr in the control group. At the conclusion of the study, all the patients had achieved adult height. Adult height was considered to be attained when the growth during the preceding year was less than 1 cm, with a BA of over 15 yr. Patients of the group treated with GH plus GnRHa showed an adult height significantly higher (P < 0.001) than pretreatment PAH (160.6 +/- 1.3 vs. 152.7 +/- 1.7 cm). Target height (TH) was significantly exceeded. The group treated with GnRH alone reached an adult height not significantly higher than pretreatment PAH (157.1 +/- 2.5 vs. 155.5 +/- 1.9 cm). TH was just reached but not significantly exceeded. The gain in centimeters obtained, calculated between pretreatment PAH and final height, was 7.9 +/- 1.1 cm in patients treated with GH combined with GnRHa; whereas in patients treated with GnRHa alone, the gain was just 1.6 +/- 1.2 cm (P = 0.001). Furthermore, no side effects have been observed either on bone age progression or ovarian cyst appearance and the gynecological follow-up in the GH-treated patients (in comparison with those treated with GnRHa alone). In conclusion, a gain of 7.9 cm in adult height represents a significant improvement, which justifies the addition of GH for 2-3 yr during the conventional treatment with GnRHa, especially in patients with CPP, and a decrease in GV so marked as to impair PAH, not allowing it to reach even the third centile.     

The mechanism of the obstruction in calcific aortic stenosis with bicuspid valve: a reason for failure of balloon aortic valvuloplasty in the elderly

Percutaneous aortic balloon valvuloplasty failed to relieve the obstruction in 2 elderly patients with calcific aortic stenosis. Intraoperative and pathologic examination showed bicuspid aortic valve with symmetric cusps, straight and fibrotic cusp edges and fractured calcific nodules of the aortic valve. Failure of balloon valvuloplasty in these patients, in spite of successful fractures of calcific nodules, was due to inability to influence the spring-like action of the thickened edges of the valve which represents a specific additional cause of obstruction in calcific bicuspid aortic valve of the elderly.     

Cleft anterior leaflet of the mitral valve with intact septa. A study of 20 cases

Twenty pathologic specimens of heart, each with a cleft in the anterior leaflet of the mitral valve not associated with septal defects of persistent common atrioventricular canal (isolated cleft of the mitral valve), were studied. In 9 cases, there were either no associated anomalies or ones not of functional significance. In each of the other 11 cases there were other significant associated cardiac anomalies, including ventricular septal defect and d-transposition of the great arteries. Functional consequences of the mitral anomaly were mitral insufficiency, subaortic stenosis, or both. Mitral insufficiency was related principally to the width of the cleft. Subaortic stenosis, when present, was due to the position of insertion of accessory chordae in the ventricular septum in a position under the commissure, between the left and right aortic cusps or under the right aortic cusp.     

Doppler echocardiography in assessing mechanical and biological heart valve prostheses

The study was performed to assess Doppler echocardiographic features of mitral and aortic prosthetic valves of different types with both normal and abnormal function. Two hundred and twenty-three patients with 250 prostheses were studied. Two hundred eight valves (111 mitral, 95 aortic and 2 tricuspid) were considered to be functioning normally after clinical examination, phonocardiography and M-mode and 2D echocardiography. This group enabled us to define normal Doppler echocardiographic findings for different types of prosthesis. In mitral position, peak (p) and mean (m) gradients were lower for disc prostheses and higher for ball and biological prosthetic valves; values of effective orifice area (A), calculated by pressure half-time method, were lower for biological and ball prostheses and higher in disc valves. Results were as follows: St. Jude (p 10.6 mmHg, m 3.9 mmHg, A 2.7 cm2), Duromedics (p 10.6, m 4.3, A 2.8), Bj?rk-Shiley (p 10.4, m 4, A 2.3), Omniscience (p 14.2, m 6.2, A 2.1), Starr-Edwards (p 15.9, m 5.4, A 2.1), Hancock (p 14.7, m 6, A 2), Carpentier (p 13.2, m 5.4, A 1.9). Mild regurgitation, considered "physiological", was found in 2/8 Carpentier valves and in 3/34 St. Jude prostheses. In aortic valves lower peak gradients were found in Lillehei (18.3 mmHg), St. Jude (23.8 mmHg), Bj?rk-Shiley (26 mmHg), Duromedics (27 mmHg) and higher values in Starr-Edwards (30.2 mmHg), Hancock (30 mmHg) and Omniscience (35.5 mmHg) prostheses. Mild regurgitation, considered "physiological", was found in 17% of Omniscience valves, 21% of Hancock, 33% of Duromedics, 45% of St. Jude, 60% of Bj?rk-Shiley prostheses. Hancock mitral valves implanted for over 7 years had a mean gradient higher than valves with a shorter period of implantation (7.6 vs 4.85 mmHg, p less than 0.1), whereas the effective orifice area was similar. Hancock aortic valves implanted for over 7 years had a peak gradient slightly higher than the other group (implantation less than 7 years previously), but the difference was not statistically significant. Forty-two valves (19 aortic and 23 mitral) were considered to be malfunctioning. Regurgitation Doppler signals of malfunctioning valves appeared different from those of "physiological" reverse flow; in the former cases forward gradient was higher than normal prostheses. In stenotic aortic prostheses, peak systolic gradient was greatly increased; in stenotic mitral prostheses, a very significant increase in mean gradient and a great decrease in effective orifice area were found. In 14 patients who underwent surgical re-operation and in the patient who died before operation, Doppler echocardiographic findings were confirmed.(ABSTRACT TRUNCATED AT 400 WORDS)     

Screening of PRKAR1A and PDE4D in a Large Italian Series of Patients Clinically Diagnosed With Albright Hereditary Osteodystrophy and/or Pseudohypoparathyroidism

The cyclic adenosine monophosphate (cAMP) intracellular signaling pathway mediates the physiological effects of several hormones and neurotransmitters, acting by the activation of G‐protein coupled receptors (GPCRs) and several downstream intracellular effectors, including the heterotrimeric stimulatory G‐protein (Gs), the cAMP‐dependent protein kinase A (PKA), and cAMP‐specific phosphodiesterases (PDEs). Defective G‐protein–mediated signaling has been associated with an increasing number of disorders, including Albright hereditary osteodistrophy (AHO) and pseudohypoparathyroidism (PHP), a heterogeneous group of rare genetic metabolic disorders resulting from molecular defects at the GNAS locus. Moreover, mutations in PRKAR1A and PDE4D genes have been recently detected in patients with acrodysostosis (ACRDYS), showing a skeletal and endocrinological phenotype partially overlapping with AHO/PHP. Despite the high detection rate of molecular defects by currently available molecular approaches, about 30% of AHO/PHP patients still lack a molecular diagnosis, hence the need to screen patients negative for GNAS epi/genetic defects also for chromosomal regions and genes associated with diseases that undergo differential diagnosis with PHP. According to the growing knowledge on Gsα‐cAMP signaling‐linked disorders, we investigated our series of patients (n = 81) with a clinical diagnosis of PHP/AHO but negative for GNAS anomalies for the presence of novel genetic variants at PRKAR1A and PDE4D genes. Our work allowed the detection of 8 novel missense variants affecting genes so far associated with ACRDYS in 9 patients. Our data further confirm the molecular and clinical overlap among these disorders. We present the data collected from a large series of patients and a brief review of the literature in order to compare our findings with already published data; to look for PRKAR1A/PDE4D mutation spectrum, recurrent mutations, and mutation hot spots; and to identify specific clinical features associated with ACRDYS that deserve surveillance during follow‐up. © 2016 American Society for Bone and Mineral Research.     

Primary angioplasty with routine stenting compared with thrombolytic therapy in elderly patients with acute myocardial infarction

Background

Prior studies have yielded conflicting data on the advantage of primary angioplasty compared with thrombolysis in elderly patients with acute myocardial infarction (AMI). These studies, however, were performed before the contemporary widespread use of intracoronary stents and glycoprotien IIb/IIIa antagonists.

Methods

We prospectively compared the outcome of 130 consecutive elderly patients (aged ≥70 years) with ST-elevation AMI who were admitted to 2 similar neighboring medical centers. Patients were assigned to receive either thrombolytic therapy with accelerated tissue-type plasminogen activator (center I) or primary angioplasty with routine stenting (center II).

Results

Of the patients assigned to receive primary angioplasty, 91% underwent stenting. At 6 months, patients treated with primary angioplasty, compared with those treated with thrombolytic therapy, had a lower incidence of reinfarction (2% vs 14%, P = .053) and revascularization for recurrent ischemia (9% vs 61%, P < .001) and a significant reduction in the prespecified combined end point of death, reinfarction, or revascularization for recurrent ischemia (29% vs 93%, P < .01). Primary angioplasty remained an independent predictor of the triple combined end point after controlling for potential covariables (relative risk 0.63, 95% CI 0.38-0.84). Major bleeding complications were also significantly reduced in the primary angioplasty group (0% vs 17%, P = .03).

Conclusions

Compared with thrombolysis, primary angioplasty with routine stenting in elderly patients with AMI is associated with better clinical outcomes and a lower risk of bleeding complications.     

Isolated cleft mitral valve: a variety of congenital mitral regurgitation identified by 2-dimensional echocardiography

Nine children with isolated cleft mitral valve, aged 1 day to 12 years, were studied. The electrocardiogram showed a normal QRS axis in 5 subjects. Cardiac catheterization was performed in 4 patients and demonstrated severe mitral insufficiency in 3 but failed to clearly demonstrate a cleft mitral valve or gooseneck deformity. The mitral cleft was confirmed at operation in 2 patients. Two-dimensional echocardiography demonstrated a cleft dividing the anterior mitral leaflet into 2 portions in each patient. The mitral anulus was normally positioned and the atrioventricular septum present. Atrial and ventricular septa were intact. Features similar to anatomic studies such as accessory chordae and thickening of the edges of the cleft with increasing age were also seen. Two-dimensional echocardiography is the only method available to reliably diagnose isolated cleft of the mitral valve.