Familial adult-onset Pompe disease associated with unusual clinical and histological features

The adult-onset form of Pompe disease had a wide clinical spectrum, ranging from asymptomatic patients with increased CK to muscle cramps and pain syndrome or rigid-spine syndrome. In addition clinical severity and disease progression are greatly variable. We report on a family with 3 siblings characterized by an unusual adult-onset Pompe disease including dysphagia and weakness of tongue, axial and limb-girdle muscles, in association with atypical globular inclusions in muscle fibres. Our study confirms the great clinical and histological variability of adult-onset Pompe disease and further supports the need of careful evaluation of bulbar function in patients affected by this pathology.Key words: Pompe disease, globular inclusions, bulbar symptomsGlycogen storage disease type II (Pompe disease or acid maltase deficiency) is a rare autosomal recessive muscular disorder characterized by deficiency of acidalfa glucosidase (GAA), determining accumulation of glycogen in the lysosomes, mainly in cardiac and skeletal muscle cells. Typical phenotypes of glycogenosis type II include the severe classic infantile form, characterized by severe muscle weakness and hypertrophic cardiomyopathy, almost invariably fatal by 12 months, a "non-classic" form presenting between 1 and 2 years of age and the lateonset form, presenting at any time after the age of 1 year, including juvenile and adult-onset subtypes, which are considered as part of a continuous clinical spectrum (1). In particular the adult-onset form presents with slowly progressive proximal lower limb and/or paraspinal muscle weakness, often followed by restrictive respiratory failure, which could be life-threatening, as it is in infants and children (2). However the clinical spectrum of adultonset form is wide, ranging from asymptomatic patients with increased CK to muscle cramps and pain syndrome or rigid-spine syndrome (2, 3). Furthermore clinical severity and disease progression is greatly variable.We report on a family with 3 siblings with an unusual adult-onset Pompe disease clinically characterized by weakness of bulbar, axial and limb-girdle muscles in association with atypical histopathological changes.     

Peptide-urea interaction

The excess enthalpies of the ternary aqueous solutions containing urea and the glycyl-glycine, glycyl-L-alanine, L-alanyl-L-alanine and sarcosyl-sarcosine diketopiperazines respectively have been determined. A weak but favourable enthalpic contribution to the interaction between these solutes is found. The difference between “strong” and “weak” interactions in aqueous solutions of non-electrolytes is stressed and the role of water in the weak, non-specific interactions, is discussed. The consequence of the weakness of the urea-peptide interactions on the binding of urea to the proteins is also briefly discussed.     

Mid-systolic Click and Echocardiographic Evidence of Mitral Valve Prolapse During Electrical Pacing

A mid-systolic click was present in a patient during three years of follow-up after implantation of a permanent transvenous pacemaker. Echocardiography revealed posterior motion of the anterior leaflet which resembled mitral valve prolapse. Both the click and echocardiographic evidence of prolapse disappeared simultaneously with resumption of sinus rhythm and during supraventricular tachyarrhythmias. With spontaneous change in the position of the electrode three years after initial implantation, both the click and the posterior motion of the mitral valve disappeared. The association of mitral valve prolapse with electrical pacing is most unusual and appears to have a distinct pathophysiological mechanism. (PACE, Vol. 4, November-December, 1981)     

Haemodynamics during sleep: old results and new perspectives

SUMMARY  After the advent of polygraphic recordings in the 1960s a great deal of interest focused on cardiocirculatory and respiratory activity during sleep.
The Bologna sleep laboratory was the first to make direct recordings of systemic arterial pressure, pulmonary arterial pressure and alveolar ventilation in normal subjects, measuring gas-blood values during different sleep stages. In the 1960s, neurophysiologists rediscovered a syndrome known to pneumologists for a decade as Pickwickian Syndrome. Polygraphic studies performed in sleep laboratoires all over Europe (Germany, France and Italy) led to a major discovery: the syndrome was not caused by respiratory overload due to obesity, but usually by the presence of obstructive apnoeas arising during sleep. By means of continuous sleep recordings, our laboratory documented the severe repercussions of apnoeas on ventilatory and cardiocirculatory functions. Hypnologists pointed to tracheostomy as the logical effective treatment for the syndrome. Surgery was first performed in Germany by Kuhlo and coworkers and then in Bologna.
In the early 1970s, following the Bologna group's research, there emerged the now accepted concept that obstruction of the upper airways is a continuum stretching from snoring to full-blown sleep apnoea syndrome. The Bologna team was also the first to conduct epidemiological surveys that indicated that snoring is a relevant risk factor for the cardiocirculatory system.
Here the trends of haemodynamic and ventilatory parameters during sleep are investigated in syndromes of obstructive respiratory failure. The conclusion is that sleep, particularly REM-sleep, exacerbates all these disorders, and the topic provides a basis for a wider look at how cardiocirculatory activity varies during sleep under normal and pathological conditions.     

The Use of the Balloon-Tipped Floating Catheter in Temporary Transvenous Cardiac Pacing

The effectiveness and safety of balloon-tipped, flow guided, electrodes for ventricular pacing as opposed to the fluoroscopy-guided semi-rigid bipolar electrodes have never been compared in a controlled study. A prospective study was therefore undertaken to compare both techniques in semi-elective and emergency procedures. Flow guided electrodes were inserted in 67 patients (group A) and semi-rigid electrodes in 44 patients (group B). The results of group A were judged to be superior to those of group B in four aspects: a) shorter time (6'45" vs. 13'30", p less than 0.0005); b) lower incidence of catheter displacement (13.4 vs. 32.0 percent, p less than 0.05); c) longer interval of time between implantation and catheter displacement (4.4 vs. 1.9 days, p less than 0.0005); d) lower incidence of serious ventricular arrhythmias during insertion (1.5 vs. 20.4 percent, p less than 0.005). Threshold at insertion was not significantly different (0.6 +/- 0.3 vs 0.7 +/- 0.2 milliampere). The superiority of flow-guided electrodes over fluoroscopy-guided electrodes persisted in the comparison of semielective insertions in groups A and B. We conclude that the flow-guided insertion technique is safer, more expeditious and more stable than the fluoroscopy-guided technique in semi-elective as well as in emergency insertions.     

Attenuation of Cisplatin Nephrotoxicity by Streptozotocin-Induced Diabetes

Attenuation of Cisplatin Nephrotoxicity by Streptozotocin-InducedDiabetes. SCOTT, L. A., MADAN, E., AND VALENTOVIC, M. A. (1989).Fundam. Appl. Toxicol 12, 530–539. The thera peutic useof cisplatin is associated with acute renal failure. The purposeof this study was to determine (a) if streptozotocin (STZ) wastoxic to renal proximal tubules and (b) the nephrotox icityof cisplatin in STZ-diabetic rats. Male Sprague-Dawley ratswere injected with STZ (55 mg/kg, ip) to induce a diabetic state.BUN and renal cortical slice uptake of p-aminohippurate (PAN)and tetraethylammonium (TEA) were not altered, relative to normoglycemicrats, 3, 16, and 28 days following STZ treatment. These resultsindicate that STZ is not toxic to renal proximal tubules. Cisplatinnephrotoxicity studies were then conducted in STZ-diabetic andnormo glycemic rats. Cisplatin nephrotoxicity was also evaluatedin diabetic rats pretreated for 8 days with insulin. Diabeticand normoglycemic rats were administered 5 mg/kg cisplatin orwater (ip). Increased kidney weight, BUN levels, glucosuna,and proteinuria were measured in normoglycemic rats 4 days aftercisplatin administration. Renal cortical TEA and lactate-stimulatedPAH uptake (p<0.05) were diminished in the normoglycemicrats 4 days after cisplatin injection. No change in kidney weight,BUN levels, or renal cortical slice accumulation of PAH andTEA was observed in diabetic rats treated with cisplatin. However,cisplatin administration to diabetic rats pretreated with insulinresulted in increased mortality, proteinurla, glucosuna andelevated kidney weight. These results indicate that the diabeticstate attenuates cisplatin nephro toxicity. Additionally, theseresults indicate that diabetes attenuation ofcisplatin nephrotoxicityis dependent on the severity of the diabetic state.     

Type II Atrial Flutter Interruption with Transesophageal Pacing: Use of Propafenone and Possible Change of the Substrate

Type II atrial flutter (AFII) is an arrhythmia which usually cannot be interrupted by atrial pacing: the underlying mechanism is considered to be a leading circle without an excitable gap. We investigated whether the administration of propafenone, an antiarrhythmic drug, which primarily decreases conduction velocity, has a beneficial effect on AFII interruption using transesophageal pacing. Twelve patients with an AFII were randomized into 2 groups in which pacing was performed without treatment (group A) or two hours after the administration of 600 mg of oral propafenone (group B). Sinus rhythm was attained in 0 of 6 patients in group A and in 4 of 6 patients in group B (P < 0.05). The baseline mean cycle length was the same in both groups (175 ± 7 (A) vs 168 ± 8 ms (B); it lengthened significantly after the administration of propafenone (219 ± 33 vs 168 ± 8 ms; P < 0.05). Propafenone did not significantly lengthen the cycle in the two patients in whom interruption of the arrhythmia was impossible. Our data show that propafenone has a facilitating effect on atrial pacing only when it significantly prolongs the cycle length of the arrhythmia, possible expression of a conversion of AFII into type I, with an anatomical substrate and an excitable gap allowing arrhythmia capture and interruption. In the two patients in whom sinus rhythm was not restored, the absence of a direct dependence of the cycle length on the change in conduction velocity induced by propafenone may be explained by the persistence of a functionally determined circuit, resistant to atrial pacing.