Rett syndrome: a wide clinical and autonomic picture.

BACKGROUND: Rett Syndrome is a neurodevelopmental disorder almost exclusively affecting females, characterized by a broad clinical spectrum of signs and symptoms and a peculiar course. The disease affects different body systems: nervous, muscolo-skeletal, gastro-enteric. Moreover, part of the symptoms are related to the involvement of the autonomic nervous system. In the Tuscany Rett Center at Versilia Hospital, we collected data from 151 subjects with a clinical diagnosis of classical or variant RTT syndrome. For each subject, we assessed the severity of the condition with clinical-rating scales (ISS, PBZ), we quantified the performance of the autonomic nervous system, and we performed genetic analysis. We used multivariate statistical analysis of the data to evaluate the relation between the different clinical RTT forms, the cardiorespiratory phenotype, the different genetic mutations and the severity of the clinical picture. Individuals were classified according to existing forms: Classical RTT and three atypical RTT: Z-RTT, Hanefeld, Congenital. A correlation between C-Terminal deletions and lower severity of the clinical manifestations was evident, in the previous literature, but, considering the analysis of autonomic behaviour, the original classification can be enriched with a more accurate subdivision of Rett subgroups, which may be useful for early diagnosis. RESULTS: Present data emphasize some differences, not entirely described in the literature, among RTT variants. In our cohort the Z-RTT variant cases show clinical features (communication, growth, epilepsy and development), well documented by specific ISS items, less severe, if compared to classical RTT and show autonomic disorders, previously not reported in the literature. In this form epilepsy is rarely present. In contrast, Hanefeld variant shows the constant presence of epilepsy which has an earlier onset In Hanefeld variant the frequency of apneas was rare and, among the cardiorespiratory phenotypes, the feeble type is lacking. CONCLUSION: A quantitative analysis of the different autonomic components reveals differences across typical and atypical forms of RTT that leads to a more accurate classification of the groups. In our cohort of RTT individuals, the inclusion of autonomic parameter in the classification leads to an improved diagnosis at earlier stages of development.

A universal DNA extraction and PCR amplification method for fungal rDNA sequence-based identification.

Accurate identification of fungal pathogens using a sequence-based approach requires an extraction method that yields template DNA pure enough for polymerase chain reaction (PCR) or other types of amplification. Therefore, the objective of this study was to develop and standardise a rapid, inexpensive DNA extraction protocol applicable to the major fungal phyla, which would yield sufficient template DNA pure enough for PCR and sequencing. A total of 519 clinical and culture collection strains, comprised of both yeast and filamentous fungi, were prepared using our extraction method to determine its applicability for PCR, which targeted the ITS and D1/D2 regions in a single PCR amplicon. All templates were successfully amplified and found to yield the correct strain identification when sequenced. This protocol could be completed in approximately 30 min and utilised a combination of physical and chemical extraction methods but did not require organic solvents nor ethanol precipitation. The method reduces the number of tube manipulations and yielded suitable template DNA for PCR amplification from all phyla that were tested.

Interlaboratory reproducibility of a single-locus sequence-based method for strain typing of Aspergillus fumigatus.

Seven international laboratories tested the recently proposed single-locus typing strategy for Aspergillus fumigatus subtyping for interlaboratory reproducibility. Comparative sequence analyses of portions of the locus AFUA_3G08990, encoding a putative cell surface protein (denoted CSP), was performed with a panel of Aspergillus isolates. Each laboratory followed very different protocols for extraction of DNA, PCR, and sequencing. Results revealed that the CSP typing method was a reproducible and portable strain typing method.

Isolation and characterization of a new fungal species, Chrysosporium ophiodiicola, from a mycotic granuloma of a black rat snake (Elaphe obsoleta obsoleta).

Isolation and characterization of the new species Chrysosporium ophiodiicola from a mycotic granuloma of a black rat snake (Elaphe obsoleta obsoleta) are reported. Analysis of the sequences of different fragments of the ribosomal genes demonstrated that this species belongs to the Onygenales and that this species is genetically different from other morphologically similar species of Chrysosporium. This new species is unique in having both narrow and cylindrical-to-slightly clavate conidia and a strong, pungent odor.

Fast track in liver transplantation: 5 years' experience.

BACKGROUND AND OBJECTIVE: Reducing postoperative mechanical ventilation in patients undergoing liver transplantation may have clinical and organizational advantages. On the basis of our experience, we here evaluate the possibility of practising immediate tracheal extubation in the operating theatre. METHODS: In this prospective study, patients consecutively undergoing liver transplantation between 1 June 1999 and 31 May 2004 were extubated in the operating theatre at the end of surgery on the basis of standardized and universally accepted criteria, under conditions of haemodynamic and metabolic stability. RESULTS: Two hundred and seven of the 354 patients (58.5%) were extubated immediately after the completion of the surgical procedure (mean time between end of surgery and extubation: 0.4 +/- 1.4 min); two were re-intubated. In the last of the 5 yr of the study, the percentage of immediate extubations increased to 82.5%. During the study period, there was a progressive increase in the number of immediate extubations per individual member of the team of anaesthetists. The pre-transplant Child-Pugh severity of the underlying liver disease did not predict rapid extubation, but the Model for End-stage Liver Disease score of < 11 did (receiver operator characteristic area under the curve = 0.61; P < 0.05). CONCLUSIONS: Immediate extubation after liver transplantation is possible in a substantial percentage of cases; confidence, habit and a spirit of emulation are decisive factors in encouraging anaesthetists to extend this practice to the largest possible number of patients. A successful immediate extubation may be an important indicator of perioperative quality of care in liver transplantation.

Very early tracheal extubation without predetermined criteria in a liver transplant recipient population.

This study of all patients undergoing orthotopic liver transplantation (OLT) at our center between January 1997 and December 1999 evaluated the feasibility and safety of very early tracheal extubation without previous selection. Anesthetic management was the same in all cases, and tracheal extubation was performed on the basis of standardized criteria routinely adopted in operating rooms throughout the world, i.e., no residual curarization or anesthetic action, ability to swallow efficiently, and stable hemodynamics. One hundred sixty-nine patients underwent 181 OLTs during the study period. Tracheal extubation was performed within 3 hours of surgery in 115 cases, 8 hours in 19 cases, and 8 to 24 hours in 10 cases. In 36 cases, artificial ventilation was required for more than 24 hours or weaning was not possible. One patient died of primary graft nonfunction within 24 hours and was excluded from the analysis. The feasibility of early extubation was influenced by the amount of intraoperative transfused blood; efficacy of kidney, cardiac, and pulmonary function; and presence of encephalopathy (P <.001). No correlation was found with age or pre-OLT severity of hepatic disease, and the postoperative period was not compromised by early weaning. Very early extubation was feasible and safe in a large number of unselected transplant recipients, thus suggesting that the definition of early tracheal extubation should be changed from 8 to 3 hours after surgery.

New hematological indices in the healthy elderly.

BACKGROUND: Recently, new indices related to erythrocytes and platelet counts have been provided by hematological analysers. The purpose of the study is to investigate these new parameters in the elderly to define their normal values and to compare them with the range provided by the manufacturer. EXPERIMENTAL DESIGN: a comparative study. SETTING: general community, geriatric and internal medicine ambulatories. PATIENTS: sixty healthy free-living elderly (cut-off: 65 years) and 66 healthy young-adults, as a control group. MEASURES: we measured the common and the new hematological parameters by H.1 Bayer technology. The new hematological parameters are red diameter width-RDW, hemoglobin distribution width-HDW, mean platelet volume-MPV, platelet diameter width-PDW, platelet hematocrit-Pct. We then compared the values of our population with the Bayer range. RESULTS: The confidence interval width of the new indices define very faster limits than the Bayer range. Statistical differences were significant only in male groups: young-adults (Y) versus elderly (E) with higher values in Y than E in RBC p=0.002, in Platelet count p=0.050 and in MPV p=0.026; and higher values in E in MCV p=0.008, MCH p=0.006 and PDW p=0.004. CONCLUSIONS: In the literature a wide range of common hematological parameters are reported in the elderly, while the new hematological values have not been discussed till now. Our results may contribute to define the laboratory limits of the new hematological values in the healthy elderly.

Blood zinc, copper and magnesium in aging. A study in healthy home-living elderly.

BACKGROUND: Blood concentrations of copper, zinc and magnesium were determined in healthy elderly to assess whether aging interferes with mineral and micronutrient status. EXPERIMENTAL DESIGN: case series. SETTING: Internal Medicine and Geriatrics ambulatories in a University Hospital in Pisa, a city of Central Italy. PARTICIPANTS: 143 healthy outpatients of both sexes, who underwent a cardiological examination. INTERVENTION: no treatment and intervention were performed. MEASURES: copper (Cu), zinc (Zn) and magnesium--both intraerythrocytic (iMg) and extracellular (eMg)--were measured. RESULTS: The concentrations of Cu and eMg were found significantly higher in the elderly: Cu 117.5 +/- 17.0 micrograms/dl in the elderly vs 102.5 +/- 19.6 micrograms/dl in the younger (p < 0.001); eMg 1.8 +/- 0.2 in the elderly vs 1.7 +/- 0.2 mEq/l in the younger (p < 0.05). On the other hand, the levels of Zn and iMg did not differ in the two groups: Zn 113.3 +/- 14.9 micrograms/dl in the elderly vs 118.0 +/- 17.3 micrograms/dl in the younger, p = n.s.; iMg 4.3 +/- 0.4 mEq/l in the elderly vs 4.2 +/- 0.4 mEq/l in the younger, p = n.s. No correlation was found between age and single elements. CONCLUSIONS: These results suggest that the healthy free-living elderly have an adequate mineral intake. Nutrient supplements may by useful in the elderly with chronic diseases, comorbidities, and polypharmacy to prevent further age dysfunctions.

Chlamydia pneumoniae and anti-infective therapy: their role in the pathogenesis and treatment of coronary artery disease.

Cardiovascular disease remains the most common cause of death in the United States; however, conventional cardiovascular risk factors fail to explain completely the pathogenesis of atherosclerosis and coronary artery disease. There has been recent interest in the association between Chlamydia pneumoniae and the risk of development or progression of atherosclerotic disease. This association has become evident through serologic, pathologic, and animal-based models and, more recently, through limited trials of antichlamydial antibiotics in humans. Whether C. pneumoniae is a causative agent or "innocent bystander" or whether antibiotic therapy has any role in the treatment of cardiovascular disease remains to be determined.

[Syncope at pediatric ages: evaluation with head-up tilt]. / La sincope in etá pediatrica: valutazione mediante head-up tilt test.

Syncope is a common medical problem with multiple potential causes and it is very frequent in pediatric population . Neurocardiogenic syncope has been increasingly recognized with the introduction of head-up tilt test (HUTT). The study investigates the clinical utility of HUTT in the evaluation and management of children with recurrent syncope and structurally normal heart. Two-hundred-forty-three consecutive young patients with recurrent unexplained syncope, 100 males and 143 females (mean age 11.4 years, range 5 to 20) underwent HUTT using a 60 degree tilt for 45 min. The test was considered positive when it provoked symptoms of syncope with hypotension and/or bradycardia. Twenty-six patients (10.7%) were positive for neurocardiogenic syncope. Of the 26 patients with the positive tilt, 5 (19.2%) had cardioinhibitory response, 5 (19.2%) mixed response and 16(61.6%) vasodepressive response. Nineteen of 143 females (13.3%) and 7 of 100 males (7%) resulted positive (NS). Among patients < 10 years of age 3/41 (9.8%) were positive and among > 10 years 22/202 patients (10.9%) resulted positive (NS). The cardioinhibitory response is more frequent in males (p = 0.01), and the vasodepressive in females (p = 0.05). In our study, concerning a non selected pediatric population a positive test resulted in a lower percentage than previously reported; moreover, the tilt test has appeared a promising method of identifying patients requiring pharmacotherapy. Additional randomized controlled studies are necessary to better define the prognosis and treatment of neurocardiogenic syncope in children and adolescents with positive tilt test. Finally, an assessment of the outcome of young patients with syncope and a negative tilt test is needed.

Tortuosity, kinking, and coiling of the carotid artery: expression of atherosclerosis or aging?

The etiology of carotid abnormalities is both congenital than acquired. The aim of this study was to clarify the role of aging and atherosclerosis in the acquired cases, and the role of these abnormalities in hemodynamic alterations and neurologic symptoms. Over a 1-year period the authors studied all the subjects undergoing carotid examination by continuous-wave and color-coded Doppler sonography at an Angiology Unit. They evaluated neurologic symptoms; risk factors for atherosclerosis; number, sites, and kinds of carotid abnormalities; atherosclerotic lesions; stenosis; hemodynamic alterations of the carotid; and other localizations of atherosclerotic diseases. There were 469 subjects: 272 (58%) with abnormalities (group 1) and 197 (42%) without abnormalities (group 2). The total number of abnormalities was 479 (104 tortuosities, 262 kinkings, and 113 coilings). The abnormalities were more prevalent in the elderly (P<0.001) and in women (P<0.001). In group 1 they found significant prevalences of hyperlipemia (P<0.001), hypertension (P<0.01), chronic cigarette smoking (P<0.01), and ischemic heart disease (P<0.05). Carotid atherosclerotic lesions were more prevalent in group 1 than in group 2 (P<0.001); among the patients with atherosclerotic carotid lesions, those in group 1 were older than those in group 2 (P<0.001). Tortuosity seemed to be associated with fewer hemodynamic alterations. The authors conclude that atherosclerosis, hypertension, and aging may play an important role in producing carotid abnormalities. The aging seemed more important than atherosclerosis. Only a prospective study of patients with carotid abnormalities and no atherosclerotic lesion will clarify the role of hemodynamics and neurologic symptomatology.

[5-Aminosalicylic acid in the prevention of recurrences of Crohn's disease]. / 5-Aminosalicylsäure in der Rezidivprophylaxe des Morbus Crohn.

AIM OF STUDY: To evaluate the efficacy of 5-aminosalicylic acid (5-ASA) in preventing recurrences of Crohn's disease. PATIENTS AND METHODS: Between January 1988 and December 1989 a total of 60 patients (37 men, 23 women, mean age 34.8 years) were selected in whom the diagnosis of Crohn's disease had been known for at least 2 years. A further criterion for inclusion was remission for at least one year in patients who had been operated or for one month in the nonoperated ones. Furthermore, the latter must have had at least one recurrence during the last year. They were in turn assigned to be treated with 5-ASA (2.4 g daily by mouth) or not treated (control). The activity and localization of Crohn's disease were defined according to the "Crohn's disease activity index" (CDAI) and the "laboratory index" (LI), as well as by endoscopy and (or) radiology. The patients were examined every 6 months for 4 years. A recurrence was diagnosed if the CDAI was more than 150 or had increased to at least 60 points above the initial value and the LI was above 100. RESULTS: 29 recurrences were noted, 72.4% within the first 2 years. 15 recurrences (46.9%) were in the treated patients and 14 (58.3%) among the untreated controls. The Kaplan-Meier curve (statistical comparison of the probability of recurrence) showed no significant difference between the two groups (P = 0.23): the recurrence rate was the same in the two groups, among the patients with or without previous operation and for different primary localizations. There were no notable side effects. CONCLUSION: Treatment with 5-ASA was not found to influence the likelihood of recurrence. Age, duration of the disease, primary localization and previous operation were not prognostic factors.

[Falls and fractures in the elderly. Causes and consequences]. / Cadute e fratture nell'anziano. Cause e consequenze.

OBJECTIVE: To evaluate the causes of non-pathologic traumatic fractures in the elderly and their consequences on quality of life. DESIGN: A prospective trial. FOLLOW-UP: 12 months for the inpatients and 3 months for the outpatients. SETTING: Basal assessment in orthopaedic hospital; follow-up in geriatric unit. PATIENTS: Both inpatients and outpatients, 65 years and over, both sexes, both living in a nursing home and in their own home, admitted to an orthopaedic hospital because of a fall, with diagnosis of a subsequent fracture. Criteria of exclusion: patients with pathologic fracture. 121 patients were enrolled, 108 had a complete follow-up. SURVEYS: Health and functional status prior to the fracture, causes and concomitant causes of the fall, site of the fracture, complications and functional disabilities. RESULTS: The most frequent cause of fracture is an accidental fall, especially in younger elderly, other causes being acute cardiovascular and neurological diseases. Fractures occur more frequently in females. The most serious injuries affect frailer subjects, with advanced age, neurologic and multiple chronic diseases. Fracture of femur is the most frequent fracture and it has the highest risk complications, functional disabilities and death. CONCLUSIONS: Because of the high frequency of accidental falls, the authors emphasize the necessity of primary prevention, especially the removal of architectural barriers both at home and in public environment.

The use of recombinant interferon alfa-2b in elderly patients with anti-HCV-positive chronic active hepatitis.

OBJECTIVE: To compare efficacy and tolerance of recombinant interferon alfa-2b in the treatment of anti-HCV-positive chronic active hepatitis (CAH) in subjects aged 65 years and above with those less than 65. DESIGN: A randomized controlled trial. SETTING: Outpatients in two hospitals. PATIENTS: 65 consecutive outpatients with anti-HCV-positive CAH for 1 to 30 years, having basal aminotransferase levels at least twice the normal value. Those 65 and over were randomized to an interferon group (A, n = 22) or a no-treatment group (B, n = 22). All those under 65 received interferon (group C, n = 21). INTERVENTION: Interferon at a dose of 3 mU 3 times a week for a 6-month period. A normalization of serum aminotransferase levels was considered a positive response to therapy. RESULTS: Response to therapy was positive in 62% of the treated elderly compared to 57% of the adults (P = 0.85). The two groups of responders showed a common highly significant reduction of aminotransferase (P < 0.001). Side effects were similar in elderly and young. Two untreated elderly showed spontaneous normalization of aminotransferase. CONCLUSION: Interferon in anti-HCV-positive CAH is useful in the elderly, allowing normalization of aminotransferase, improvement of the histology and remission of the disease in 62% of the cases. Side effects seem to be independent of age. Further studies are required to assess both duration of remission and usefulness of cyclic therapy in previous responders.

[Clinical evaluation of anemia in the aged]. / Valutazione clinica dell'anziano anemico.

Of 533 patients over 65 years old (153 males and 380 females), admitted to geriatric units for various medical diseases, 111 (20.8%) were anemic. Among males the prevalence of anemia was 30.1%, among females 17.1%. Three principal causes of anemia were revealed. The most frequent (42.3%) was microcytic, hypochromic anemia, with low levels of serum iron concentrations, related to gastrointestinal diseases (with chronic occult blood loss). 38.7% of anemic elderly people was affected by chronic diseases. In 19.0% a folate (16 case) and iron (5 cases) deficiency was revealed. These results suggest that anemia in the elderly is always pathological; hemoglobin values lower than 12 g/dl should be considered abnormal and investigated.

[Sodium and diseases in the aged]. / Sodio e malattie nell'anziano.

The authors describe serum sodium levels in elderly patients at hospitalization and evaluate the role attributable to drugs, diseases, nutrition and fluid balance. Among 167 patients (average age 75.29 +/- 7.14), 132 (79.04%) had normal sodium balance, 34 (20.36%) were hyponatremic and only 1 (0.60%) was hypernatremic. Patients who had serum sodium levels above 129 mEq/l were asymptomatic. In five cases hyponatremia was acute and severe (less than or equal to 127 mEq/l). Seven patients who had serum sodium levels less than 127 mEq/l presented psychiatric and neurological manifestations, which subsided completely after prompt correction of the electrolyte disorder. The authors suggest that the pathogenesis of hyponatremia in pathological states in the elderly is complex, although iatrogenic causes play a fundamental role.