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Ataxia telangiectasia (AT) is a rare neurodegenerative genetic disorder due to bi-allelic mutations in the Ataxia Telangiectasia Mutated (ATM) gene. The aim of this paper is to better define the immunological profile over time, the clinical immune-related manifestations at diagnosis and during follow-up, and to attempt a genotype–phenotype correlation of an Italian cohort of AT patients. Retrospective data of 69 AT patients diagnosed between December 1984 and November 2019 were collected from the database of the Italian Primary Immunodeficiency Network. Patients were classified at diagnosis as lymphopenic (Group A) or non-lymphopenic (Group B). Fifty eight out of 69 AT patients (84%) were genetically characterized and distinguished according to the type of mutations in truncating/truncating (TT; 27 patients), non-truncating (NT)/T (28 patients), and NT/NT (5 patients). In 3 patients, only one mutation was detected. Data on age at onset and at diagnosis, cellular and humoral compartment at diagnosis and follow-up, infectious diseases, signs of immune dysregulation, cancer, and survival were analyzed and compared to the genotype. Lymphopenia at diagnosis was related per se to earlier age at onset. Progressive reduction of cellular compartment occurred during the follow-up with a gradual reduction of T and B cell number. Most patients of Group A carried bi-allelic truncating mutations, had a more severe B cell lymphopenia, and a reduced life expectancy. A trend to higher frequency of interstitial lung disease, immune dysregulation, and malignancy was noted in Group B patients. Lymphopenia at the onset and the T/T genotype are associated with a worst clinical course. Several mechanisms may underlie the premature and progressive immune decline in AT subjects.

Astute control of brain activity states is critical for adaptive behaviours and survival. In mammals and birds, electroencephalographic recordings reveal alternating states of wakefulness, slow wave sleep and paradoxical sleep (or rapid eye movement sleep). This control is profoundly impaired in narcolepsy with cataplexy, a disease resulting from the loss of orexin/hypocretin neurotransmitter signalling in the brain. Narcolepsy with cataplexy is characterized by irresistible bouts of sleep during the day, sleep fragmentation during the night and episodes of cataplexy, a sudden loss of muscle tone while awake and experiencing emotions. The neural mechanisms underlying cataplexy are unknown, but commonly thought to involve those of rapid eye movement-sleep atonia, and cataplexy typically is considered as a rapid eye movement sleep disorder. Here we reassess cataplexy in hypocretin (Hcrt, also known as orexin) gene knockout mice. Using a novel video/electroencephalogram double-blind scoring method, we show that cataplexy is not a state per se, as believed previously, but a dynamic, multi-phased process involving a reproducible progression of states. A knockout-specific state and a stereotypical paroxysmal event were introduced to account for signals and electroencephalogram spectral characteristics not seen in wild-type littermates. Cataplexy almost invariably started with a brief phase of wake-like electroencephalogram, followed by a phase featuring high-amplitude irregular theta oscillations, defining an activity profile distinct from paradoxical sleep, referred to as cataplexy-associated state and in the course of which 1.5-2 s high-amplitude, highly regular, hypersynchronous paroxysmal theta bursts (∼7 Hz) occurred. In contrast to cataplexy onset, exit from cataplexy did not show a predictable sequence of activities. Altogether, these data contradict the hypothesis that cataplexy is a state similar to paradoxical sleep, even if long cataplexies may evolve into paradoxical sleep. Although not exclusive to overt cataplexy, cataplexy-associated state and hypersynchronous paroxysmal theta activities are highly enriched during cataplexy in hypocretin/orexin knockout mice. Their occurrence in an independent narcolepsy mouse model, the orexin/ataxin 3 transgenic mouse, undergoing loss of orexin neurons, was confirmed. Importantly, we document for the first time similar paroxysmal theta hypersynchronies (∼4 Hz) during cataplexy in narcoleptic children. Lastly, we show by deep recordings in mice that the cataplexy-associated state and hypersynchronous paroxysmal theta activities are independent of hippocampal theta and involve the frontal cortex. Cataplexy hypersynchronous paroxysmal theta bursts may represent medial prefrontal activity, associated in humans and rodents with reward-driven motor impulse, planning and conflict monitoring.

Concurrent chemoradiotherapy has become the standard of care for patients with inoperable squamous cell head and neck carcinoma. More recently, induction chemotherapy has been adopted as an approach in the management of these patients. We report the results of a phase II trial associating induction chemotherapy and concomitant chemoradiotherapy in a series of patients with inoperable squamous cell head and neck cancer. Twenty-nine patients with advanced squamous cell carcinoma ineligible for surgery were enrolled. Induction chemotherapy with docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) every 21 days was administered for two cycles. Radiotherapy followed the induction phase. During radiotherapy, docetaxel was administered weekly at the dose of 33 mg/m(2) . Primary end point of the study was feasibility of treatment. Six (18%) patients failed to conclude the treatment schedule. Although response rates in evaluable patients were very high (disease control rate90%), toxicities were a matter of concern. The reported treatment schedule proved infeasible. However, some modifications in ancillary therapies aimed at exploiting its efficacy could make it practicable.

Alterations of the vestibulo-ocular reflex, optokinetic nystagmus, and visuo-vestibular-ocular reflex, have already been described in patients with AIDS and HIV-1 positive asymptomatic subjects. The introduction to the clinical practice of posturographic techniques allows us to study, with precision, postural perturbation that may be present when performing Romberg’s test and to study the vestibulo-spinal reflex as a component of the vestibular system. The relative lack of studies on posturography and AIDS, encouraged us to continue our research on the vestibular system both in asymptomatic HIV-1 seropositive patients and in patients with AIDS (IV stage according to the classification proposed by the Centre for Disease Control). Recordings were made in group 1 (control group, 55 normal subjects), in group 2 (15 asymptomatic HIV-positive subjects), and in group 3 (15 patients with AIDS stage IV). Static and dynamic posturography were carried out using Tonnies platform system (Tonnies GmbH & Co., Wurzburg, Germany) and the data were analysed with Tonnies Posturographic Tübingen (TPOST) software vers. 5.19. In asymptomatic HIV+ subjects, we observed an increase in RW, RA and M3 reflex latency. AIDS patients (stage IV) exhibited significant alterations in almost all the posturographic parameters and the electromyographic potentials. Our results validate static and dynamic posturography as a method for otoneurological investigation and appear to confirm that the entire vestibular system is involved since the earliest stages of the HIV infection. In the HIV+ subjects, a variable dysfunction in the reflex control to long latency was observed, which is correlated with the alteration of the central dopaminergic system; in AIDS patients, the central nervous system damage appears more important, globally distributed and correlated also with immunosuppression.

Although quality of life (QoL) has become an important aspect of cancer rehabilitation, psychometric studies on thyroid cancer patients are rare. We performed a case-controlled study on QoL in patients with differentiated thyroid carcinoma (DTC). QoL was evaluated in 61 patients with a history of DTC diagnosed from1 to 23 yr earlier. An undetectable thyroglobulin (Tg) level after recombinant human TSH (rhTSH) testing was considered the best predictor of cure. QoL was evaluated by means of a general psychiatric interview, the self-rating Kellner Symptoms Questionnaire (KSQ) and the Hamilton Depression Scale (HDS). QoL was also evaluated in a control group of subjects on L-T4 therapy with a non-toxic multinodular goiter diagnosed from1 to 25 yr earlier. DTC and control subjects were similar in age, male-female distribution and concomitant psychiatric therapies. Per-week dosage of L-T4 was higher in DTC patients than in controls (p0.01). In neither group of subjects was there any correlation between current TSH levels or interval from diagnosis and KSQ or HDS scores. Only in DTC patients was there a positive correlation between age and KSQ (p0.05) or HDS (p0.01) scores. There was a significant difference in overall KSQ scores between DTC (33.4 +/- 2.1) and control (24.5 +/- 1.9; p0.01) subjects. The subscales of KSQ showed a significant inter-group difference. HDS scores were higher in DTC subjects (35.8 +/- 1.0) than in controls (30.0 +/- 1.1; p0.01). HDS score was significantly (p = 0.02) higher in female than in male DTC patients. In patients with papillary carcinoma there was a positive correlation between the MACIS (metastases, age, completeness, invasiveness, size) score and KSQ (p = 0.01) or HDS (p0.01) scores. After rhTSH testing, detectable Tg levels were found in 13% of DTC patients. In Tg-positive patients, KSQ and HDS scores were not different from those of Tg-negative patients. After an 8-14 month period, a significant decrease in the KSQ scale somatization (p = 0.02) was found in a sub-set of 31 DTC patients. In conclusion, even in the age of rhTSH testing, DTC patients suffer an impairment of their QoL, as noted when short-term L-T4 withdrawal was the gold standard. Longitudinal evaluation seems to indicate a slight improvement in QoL when safe rhTSH testing is extensively used in the management of the disease.

Background: Restoration of intestinal continuity in patients with ileostomy after total colectomy or with colostomy after Hartmann's procedure is a major operation. Herein we illustrate the validity of gasless laparoscopically assisted reversal using abdominal wall lifting. Methods: The operation was performed on 10 patients from February 1997 to May 1999. Seven of them had a left iliac stoma after a Hartmann resection, and three had an ileostomy after total colectomy. Results: The laparoscopic reversal was completed in eight patients; the two others were converted to an open procedure. Three major complications occurred (30%). There were no deaths. The average operation time was 192 min (range, 125-265). Time of discharge from surgery averaged 9.5 days. Mean follow-up of these patients was 12 months and negative. Conclusions: Laparoscopically assisted ileo- or colorectal anastomosis without pneumoperitoneum and using a laparotenser can be considered for the reversal of patients with ileostomy or colostomy. Even taking the high rate of intraoperative or postoperative complications into consideration, the advantages that make such a laparoscopic approach suitable include reduced trauma related to a second major abdominal operation, reduced postoperative pain, and fewer cutaneous tissues exposed to bacterial contamination. Moreover, the use of a laparotenser makes it possible to operate on elderly patients with cardiovascular diseases. In the absence of pneumoperitoneum, it becomes possible to use traditional instruments, with a consequent reduction in costs.

We studied the behaviour of Vestibular Nystagmus (VOR), of Optokinetic Nystagmus (OKN) and of Visuo-Vestibular-Ocular-Reflex (VVOR) in seven normal subjects and in thirty-two patients who had undergone cervical trauma in an automobile accident with the so called "whiplash mechanism". Thirteen subjects underwent examination within the first three months after the accident (first group), six subjects between the third and the sixth months (third group). Ocular movements was recorded according to the usual method by means of a Tonnies electronystagmograph with eight channels. The subjects, head blocked, sat on a Tonnies rotatory chair Pro model which was placed in the middle of a rotatory cylindrical chamber 2 metres in diameter and 1.9 metres in height. The width internal area was covered with thirty-two black vertical contrast. The rotatory cylinder was lighted from above by a 100 W bulb and was driven by a direct current engine which turned it clockwise and counterclockwise up to 200 degrees/sec., maximum speed, with preset acceleration ranging from 1 degree to 2 degrees/sec. All the subjects underwent to Rotatory Vestibular Stimulation by Stop test from a constant angular velocity of 90 degrees/sec. with clockwise and counterclockwise rotation, "stare type" Optokinetic stimulation with a cylinder rotation velocity of 30 degrees/sec. for 60 seconds and to contemporary Rotatory Vestibular and Optokinetic Stimulation (VVOR) so that OKN was VOR counterdirectional. The results of our experience show a statistically significative mean gain decrease of VOR and VVOR nystagmus (beating OKN direction) calculated on the first three beats in the patients of the first group and a significative increase of OKN mean gain in all the patients of the three groups. Furthermore, in sixteen out of thirty-two patients (seven in the first group, two in the second and seven in the third) we observed (during VVOR examination, immediately after stop) a nystagmus beating VOR direction lasting from 3 to 15 seconds.

The aim of our retrospective study was to verify the results of surgical treatment of rectal cancer in a homogeneous case series, evaluating the various factors that can influence the prognosis and long-term results. The prognostic factors taken into consideration were: Duke's stage; grading; colloid component; location of tumour; type of surgical intervention; age; sex; duration of the symptoms; length of normal rectum below the lower border of the tumour correlated to stage and grading. One hundred and sixty-five patients were operated with a radical approach: 50 abdominoperineal resections (APR) and 115 sphincter-saving resections (SSR) were performed. There were 90 males and 75 females. The mean age was 63 years. Total survival was 61.7% after 5 years and 50% after 10 years. In our study neither the age nor the sex, duration of symptoms or location of the tumours proved to have an influence on survival; while Duke's state turned out to be decisive for survival; also the colloid tumour component proved to have a worse prognosis. The 5-10-year survival rate was respectively 53.6% and 49% in the APR and 65.7% and 50.9% in the SSR (p = n.s.). The data we have collected show that APR and SSR operations have analogous efficiency.

During sonographic (US) studies of the neck for the nodal staging of patients with laryngeal neoplasms, the authors observed that, especially in advanced cases, also the primary lesion could be imaged with this method. Therefore, US capabilities were investigated in assessing the local stage of laryngeal neoplasms; the results were compared with clinical and surgical findings. Fifty normal subjects of various ages were previously examined to assess the normal US anatomy of laryngeal structures. The presence of calcifications within the thyroid cartilage is the major obstacle to US imaging of the larynx and is directly related to age; indeed, only 40% of subjects can be examined at the age of 70. Seventeen patients with advanced laryngeal tumors were examined by US. Laryngeal imaging was possible, either in part or completely, in 16 of 17 cases. The results were in agreement with clinical staging in 14 cases; in 2 cases US proved clinical understaging by detecting lesion spread to anterolateral perilaryngeal structures. To conclude, US is not suggested as the method of choice in patients with laryngeal neoplasms. However, in subjects with advanced tumors, also US can image the lesion directly, and even detect tumor spread to surrounding tissues, especially in the anterior and lateral directions. In a few cases, this can contribute to preoperative staging and to select the correct therapeutic approach.

The use of intravenous immunoglobulins (IVIG) has provided a substantial therapeutic advance in the treatment of antibody deficiency syndromes improving the quality of life of the affected patients. Among the advantages there are the possibility to employ higher doses to reach higher serum levels, with a more efficacious prophylaxis against infections; the prevention of chronic lung disease if IVIG are prescribed early, at diagnosis or at least at the onset of symptoms; the significant improvement of pulmonary function. The IVIG which are likely to be the best choice are the "intact Fc" preparations. In these products, or at least in some preparations, all IgG subclasses are present, which are endowed with specific and differentiated functions. Another important requirement is the presence of specific antibodies (e.g. anti Mycoplasmas, anti Campylobacter, anti Echovirus, anti pyogenic bacteria). The benefits of the prophylactic use of IVIG in preterm and low birthweight infants to prevent neonatal and late-onset infections are widely accepted. Lastly, IVIG are employed successfully in some autoimmune diseases as PTI and immune cytopenias, myasthenia gravis, acute and chronic inflammatory demyelinating polyneuropathy, Kawasaki syndrome, childhood recurrent seizures, juvenile chronic arthritis.

This study was undertaken to determine the results of resection of hepatocellular carcinoma in cirrhotic patients in Europe, using the same criteria as in the Orient for detection, surgical management, and pathology of the tumors. Seventy-two patients had a liver resection. One- and 3-yr survival rates were 68% and 51%, respectively. Survival rate was significantly higher in Child's/Pugh's class A than in class B-C patients. Patients with a thickly encapsulated tumor lived longer than those with an infiltrating tumor and had in addition a significantly lower incidence of cancer recurrence. Class A patients with a thickly encapsulated hepatocellular carcinoma had a 77% 3-year survival rate. There was no relation between the size of the tumor or the presence of symptoms and survival. These data suggest that good results can be achieved by resection of hepatocellular carcinomas in European cirrhotic patients. A thickly encapsulated tumor and an adequate liver function are the main determinants of low cancer recurrence and high survival. The clinical results in this series are similar to those reported from the Orient.

The relative lack of data on the dynamic posturography led us to start a study in order to give our contributions to the standardization of M1, M2, M3, response parameters in normal subjects. Our research was carried out on 35 normal subjects aged 21 to 50. All of them were standing in Romberg's position on a Tönnies model board in a normally lit and ventilated room. We performed two tests: the first one open-eyed staring at no point, the second, 5 minutes later, closed-eyed. The EMG signals were obtained by surface electrodes on triceps sural and front tibial muscles. The EMG recording was determined by a "tilt" movement of the board at a steady speed of 50 per sec. and 4 wide. We use a XT 286 IBM computer with "T POST" software for checking and testing the data. Our results showed a significant variation in the value of the duration parameter in open-eyed and closed-eyed tests. Latency and area values were inferior to those obtained by other authors, except for Diener and Dichgans (3) whose results differ in latency value only.

Sixteen gastrectomized patients underwent surgical treatment for alkaline reflux gastritis by means of a Roux-en-Y loop duodenal diversion. Long-term evaluation of results was performed 5-9 years later. Ten patients (62.5%) showed good results, with absence of digestive symptoms and with an increase in body weight. Two patients (12.5%) had moderate results, with presence of sporadic and mild epigastric pain. Four patients (25%) had unsatisfactory results, with persistence of epigastric pain and absence of body weight increase. No patient had recurrent biliary vomiting or endoscopic evidence of endogastric biliary reflux. Among the six patients with moderate and unsatisfactory results, two had a significant alcoholic intake, two showed a high degree of anxiety on psychological assessment, and two had both factors. Alcoholism and psychological disturbances should be considered exclusion criteria when evaluating a gastrectomized patient for surgical cure of alkaline reflux gastritis.

A 60-yr old Italian woman presented with repeated gastrointestinal hemorrhages due to ruptured esophageal varices. No evidence of liver disease could be demonstrated by laboratory tests or by multiple liver biopsies. Angiography revealed a patent portal trunk and the presence of esophageal varices. A side-to-side portacaval shunt was performed, which caused the disappearance of the esophageal varices. There was no recurrent digestive hemorrhage during a 24-month follow-up. A mild deterioration of liver function was demonstrated by laboratory data 16 months after surgical operation and some mild episodes of hepatic encephalopathy occurred. This case can be considered an example of idiopathic portal hypertension, a rare pathological condition with a higher prevalence in certain geographical areas. Its etiology is not known. One important aspect of this entity is its potential to evaluate the effects of surgical portacaval shunt procedure in the absence of liver damage.

Mortality due to recurrent variceal esophageal bleeding secondary to portosystemic shunt thrombosis is high. Early diagnosis of shunt thrombosis is therefore necessary. For these reasons, patients who have undergone a portal diversion must be controlled periodically. To this end, frequent controls, using reliable, riskless and inexpensive methods are needed. In this work, 34 patients who underwent different types of portal systemic shunts were studied by ultrasonography. Diagnosis by ultrasonography (confirmed by radiography showing esophageal varices and sometimes by arteriography) was positive with direct vision of the anastomosis in 65 p. 100 of cases and with indirect signs of patency or thrombosis of the anastomosis in 32 p. 100 of cases. This method failed to conclude in 3 p. 100 of our cases.

Between the years 1981 and 1983 we treated with Ceftriaxone (Cx) 34 children--aged 15 days to 13 years--affected with serious infections: 18 infections of lower respiratory tract, 1 sepsis caused by E. Coli, 1 meningitis with cloudy cerebrospinal fluid, 1 submandibular adenitis with otitis, 1 otitis, 12 infections of the urinary tract caused by Proteus mirabilis, E. Coli, Klebsiella oxitocica and Klebsiella pneumoniae. Whenever bacteria were isolated by cultures, sensibility in vitro to Cx was tested. Cx was given i.m. or i.v. at a dose ranging from 50 to 135 mg/Kg/die according to the age and the seriousness of the infections; in 17 children Cx was administered once daily, in the other patients in two divided doses. The following laboratory measurements were obtained before, during and after treatment: complete blood cell count, platelet count, total bilirubin, creatinine, SGOT, SGPT, alkaline phosphatase and urinalysis. Patients were also monitored daily for clinical signs and symptoms such as fever, general conditions, heart rate, respiratory rate, blood pressure. Twenty children showed a good clinical response (1 sepsis, 1 otitis, 1 adenitis, 1 meningitis, 12 infections of the urinary tract, 4 infections of the lower respiratory tract); urine sterilization was achieved after three days of therapy in all patients with infections of the urinary tract. Remarkable clinical and radiological improvement in 9 patients with infections of lower respiratory tract was observed while in only 4 children with bronchopneumonia therapy was ineffective although the dosage of Cx was adeguate; in these patients a further antibiotic treatment was necessary for a complete recovery.(ABSTRACT TRUNCATED AT 250 WORDS)