SCN4A mutation as modifying factor of myotonic dystrophy type 2 phenotype.

In myotonic dystrophy type 2 (DM2), an association has been reported between early and severe myotonia and recessive chloride channel (CLCN1) mutations. No DM2 cases have been described with sodium channel gene (SCN4A) mutations. The aim is to describe a DM2 patient with severe and early onset myotonia and co-occurrence of a novel missense mutation in SNC4A. A 26-year-old patient complaining of hand cramps and difficulty relaxing her hands after activity was evaluated at our department. Neurophysiology and genetic analysis for DM1, DM2, CLCN1 and SCN4A mutations were performed. Genetic testing was positive for DM2 (2650 CCTG repeat) and for a variant c.215C>T (p.Pro72Leu) in the SCN4A gene. The variation affects the cytoplasmic N terminus domain of Nav1.4, where mutations have never been reported. The biophysical properties of the mutant Nav1.4 channels were evaluated by whole-cell voltage-clamp analysis of heterologously expressed mutant channel in tsA201 cells. Electrophysiological studies of the P72L variant showed a hyperpolarizing shift (-5 mV) of the voltage dependence of activation that may increase cell excitability. This case suggests that SCN4A mutations may enhance the myotonic phenotype of DM2 patients and should be screened for atypical cases with severe myotonia.

Functional analysis of expression of human ecto-nucleoside triphosphate diphosphohydrolase-1 and/or ecto-5'-nucleotidase in pig endothelial cells.

Adenine nucleosides and nucleotides are important signaling molecules involved in control of key mechanisms of xenotransplant rejection. Extracellular pathway that converts ATP and ADP to AMP, and AMP to adenosine mainly mediated by ecto-nucleoside triphosphate diphosphohydrolase 1, (ENTPD1 or CD39) and ecto-5'-nucleotidase (E5NT or CD73) respectively, is considered as important target for xenograft protection. To clarify feasibility of combined expression of human ENTPD1 and E5NT and to study its functional effect we transfected pig endothelial cell line (PIEC) with both genes together. To do this we have produced a dicistronic construct bearing F2A sequence in frame between human E5NT and human ENTPD1 coding sequences. PIEC cells were mock-transfected as transfection control or transfected with plasmids encoding human ENTPD1 or human E5NT. PIEC cells were exposed to 50 µM ATP or 50 µM ADP or 50 µM AMP. Conversion of extracellular substrates into products (ATP/ADP/AMP/adenosine) was measured by HPLC in the media collected at specific time intervals. Following addition of AMP, production of adenosine in the medium of E5NT/ENTPD1- and E5NT- transfected cells increased to 14.2±1.1 and 24.5±3.4 µM respectively while it remained below 1 µM in controls and in ENTPD1-transfected cells. A marked increase of adenosine formation from ADP or ATP was observed only in E5NT/ENTPD1-transfected cells (11.7±0.1 and 5.7±2.2 µM respectively) but not in any other condition studied. This study indicates feasibility and functionality of combined expression of human E5NT and ENTPD1 in pig endothelial cells using F2A sequence bearing construct.

Power spectral analysis of heart rate in subjects over a hundred years old.

Altered autonomic regulation of cardiac function may contribute to the onset of cardiovascular disease and provide a substrate for malignant ventricular arrhythmias. This study was designed to assess cardiovascular neuroautonomic status in healthy subjects with short-term power spectral analysis of heart rate variability, including a group over 100 years of age, to identify a neuroautonomic pattern that could help to protect ultra-centenarians against cardiovascular disease. One hundred and twelve subjects (22 men and 90 women, age range 20 to 107 years) were subdivided into five age groups: <40 years (N=26, mean age 30.6+/-0.9); 41 to 60 years (N=27, mean age 51.9+/-1.2); 61 to 80 years (N=37, mean age 70.3+/-1.1); 81 to 100 (N=10, mean age 85.2+/-0.8) and older than 101 years (N=13, mean age: 103.6+/-0.6). Power spectral analysis with autoregressive algorithm provides two indexes of autonomic activity: a low-frequency component oscillating around 0.10 Hz, mainly reflecting sympathetic activity and a high-frequency component around 0.30 Hz, reflecting parasympathetic activity. Subjects 40 years of age or younger had significantly higher spectral high-frequency power values expressed in logarithmic form than the other age groups (P<0.05), the age group from 41 to 100 years had values similar to those of the other groups. However, the age group over 101 years had significantly higher values than the group from 81 to 100 years (P<0.05). Low-frequency spectral density expressed in logarithmic form and in normalized units decreased with age (P<0.0001). These data confirm an age-related decline in sympathetic activity. Compared with elderly subjects from 81 to 100 years of age ultra-centenarians have significantly higher spectral parasympathetic indexes. Parasympathetic predominance may be the neuroautonomic feature that helps to protect ultra-centenarians against cardiovascular disease.

Ferromagnetic Mn(II).Cu(II) Exchange in the New Bimetallic Quasi-2-D Compound Cu(op)(2)MnCl(4) (op = 1,4-Diazacycloheptane).

The synthesis, crystal structure, and magnetic properties are reported for the new bimetallic compound Cu(op)(2)MnCl(4), where op = HN(CH(2))(5)NH. The compound, C(10)H(24)N(4)Cl(4)CuMn, crystallizes in the monoclinic space group P2(1)/n. Cell dimensions are as follows: a = 15.316(3) Å, b = 16.608(3) Å, c = 7.141(2) Å, beta = 100.01(5) degrees, Z = 4. The structure consists of well-separated and magnetically equivalent layers which are composed of chloride-bridged Cu(op)(2)MnCl(4) binuclear units connected by rather loose Cu-N-H.Cl-Mn contacts. The MnCl(4) fragment approximates tetrahedral symmetry. The Cu(II) geometry is (4 + 1) square-pyramidal with the apical position occupied by a bridging chloride ligand and the basal ones by the nitrogen atoms from the organic ligands. The shortest interlayer M.M separations, approximately 7 Å, are of the Mn.Cu type. Magnetic susceptibility and single-crystal EPR measurements for the compound have been carried out over the range 4-300 K. At room temperature the chiT product (per MnCu unit) has a value of 4.84 emu.mol(-)(1).K, close to that expected for uncoupled S = (5)/(2) and S = (1)/(2) spins. When the temperature is lowered, chiT remains almost constant until 80-90 K, slightly increases to reach a maximum at approximately 13 K (5.21 emu.mol(-)(1).K), and then rapidly decreases. Comparison between theory and experiment, made with use of both a mean field corrected dimer model and an approximate 2-D model, indicates that Mn(II).Cu(II) exchange is ferromagnetic within the dimers (J(1) approximately 2.6 cm(-)(1)) and antiferromagnetic among dimers, with J values between -0.07 and -0.03 cm(-)(1) (the interaction Hamiltonian is of the form H = -2JS(A).S(B)). Single-crystal EPR spectra recorded along the a, b, and c axes show a large temperature dependence of the g factors: at 4.2 K, g(a) = 2.10, g(b) = 1.96, and g(c) = 2.01. This pattern substantiates the presence of a 2-D magnetic structure with ferromagnetic intradimer exchange and interdimer antiferromagnetic exchange of weaker magnitude. The opposite signs of the interactions are ascribed to the local symmetries of the Cu(II) and Mn(II) ions.

Axillary neuropathy in volleyball players: report of two cases and literature review.

Two cases of isolated neuropathy, not consequent to acute trauma, of the axillary nerve of young volleyball players are described. Interest in the pathology derives from the rarity of such case reports and the fact that the pathogenesis may be linked to a specific sporting activity. The lesion site is thought to be in the quadrilateral space.

Functional status and well-being of centenarians.

Data regarding a sample of 109 centenarians are presented, living in the region of central Italy. Physical and psychosocial variables were analyzed by a questionnaire based on a multidimensional conceptualization of health. Objective and laboratory data were collected and functional capacity was complemented by clinical diagnoses and judgements as well as by self-reported health problems and functional limitations. The results reveal that people can reach their maximum life span while maintaining good levels of functional capacity in spite of the chronological age. One major aspect of functional status in upper ranges of human life span is the everyday competence in the activities of daily living (ADL). In this regard, 26.6% of centenarians are classified as having no ADL-dependency (level A: 34.6% of males and 24.0% of females); the most frequent type of dependency was in bathing (65.1%; 46.2% of males, 71.1% of females) and in continence (45.9%; 50% of males, 44.6% of females). The Mini Mental State Examination (MMSE) showed a mean score of 19.86 +/- 5.93 (21.04 +/- 5.33 of males; 19.49 +/- 6.10 of females). The Geriatric Depression Scale (GDS) mean score was 8.22 +/- 4.89 (7.60 +/- 5.05 of males, 8.40 +/- 4.87 of females).

Autopsy study of very old hospitalized patients.

All autopsies (n = 63) performed over the period from January 1, 1989 to December 31, 1990 on patients older than 85 years who died at the Policlinico Umberto I of Rome were reviewed retrospectively. The purpose of the study was to determine the autopsy rate, to ascertain accordance between clinical and pathological diagnoses and to clarify problems in diagnosis and complications of geriatric management in our University Hospital. The autopsy rate was 12.1%. The diagnostic error was particularly high for pulmonary embolism. In 26% of cases both the causes of death and the major clinical diagnoses were confirmed.

Autonomic diabetic neuropathy: skin sympathetic response and neurovegetative cardiovascular functionality tests.

One hundred and twelve diabetic patients were submitted to several tests for evaluation of autonomic cardiovascular and sudomotor function. It was found that a patient could be positive to one test and negative to others, thus confirming the presence of sectorial lesions which do not affect the autonomic nervous system uniformly. The parasympathetic system is more frequently and precociously affected than the sympathetic system. The tests used for investigating the sympathetic component, the sympathetic skin response (SSR) gives results which are more frequently and precociously altered.

Functional gut disorders and health care seeking behavior in an Italian non-patient population.

We conducted a survey on functional gut disorders and health care seeking behavior in a large non-patient population of an Italian region (Umbria). 533 subjects were interviewed by means of a specific questionnaire. 44 (8.5%) reported symptoms compatible with the irritable bowel syndrome, 30 (5.8%) had non-colonic pain, 48 (9.2%) chronic constipation, and 20 (3.8%) dyspepsia. It is concluded that in our region there is a relatively high percentage of subjects that do not commonly seek health care, although affected by functional gut disorders.