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Duchenne muscular dystrophy (DMD) is the most common single-gene lethal disorder. Substantial patient-patient variability in disease onset and progression and response to glucocorticoids is seen, suggesting genetic or environmental modifiers.

To assess whether pegylated interferon alpha (PEG-IFN) may induce peripheral neuropathy or antibodies to peripheral nerve antigens in patients with hepatitis C virus (HCV) infection.

Objective. To examine health-related quality of life (HRQOL) in Italian patients with systemic lupus erythematosus (SLE) and compare it with that of healthy people, and to investigate relationships among different dimensions and subscales of a generic health status measure.Methods. The Medical Outcomes Study Short Form-36 (SF-36) was applied in a cohort of 126 consecutive SLE patients and 96 healthy controls. At the time of HRQOL testing, all patients underwent clinical and laboratory evaluation.Results. Both physical (PCS) and mental (MCS) component summary scores of the SF-36 were reduced in patients compared with controls. In SLE great variability in all the subscales was observed. Significant correlations between PCS and MCS and between many different subscales were observed in patients but not in controls. The PCS was higher than MCS more frequently in controls than in SLE patients (81 vs 48.4%, P<0.00001). In SLE, HRQOL tended to worsen with age.Conclusion. Both PCS and MCS contribute to the decrease in HRQOL in SLE patients. In SLE the mutual interaction between these two dimensions seems to be more relevant than in healthy people.

Objective. To investigate the role of clinical, immunological and psychological variables in influencing the health-related quality of life (HRQOL) of Italian patients with systemic lupus erythematosus (SLE).Methods. The Medical Outcomes Study Short Form-36 was applied in a cohort of 126 SLE patients. At the time of HRQOL testing all patients underwent a clinical and laboratory evaluation, together with the measure of disease activity, severity and damage. In addition, a battery of psychological tests including the Hamilton Anxiety Scale (HAS) and the Hamilton Depression Rating scale (HAM-D) was applied.Results. The parameters which seemed to greatly influence the impairment of HRQOL were older age, arthralgia–arthritis and higher HAS scores as well as HAM-D. In multivariate analysis (adjusted for age), arthralgia–arthritis and a higher HAM-D score were associated with HRQOL impairment. No relationship between HRQOL and SLE activity, severity or damage were found. However, a relationship between HAS or HAM-D scores and damage or arthralgia–arthritis was noted.Conclusion. Anxiety, depression and joint pain seem to be the major determinants of HRQOL impairment in SLE patients. Damage seems to influence HRQOL mostly through depression.

The initial studies on nitrosoureas were performed >30 years ago. These drugs remain the standard chemotherapy for glioblastoma. However, because the criteria used to evaluate the activity of nitrosoureas in a neuro-oncologic setting have changed, new data on their activity are needed.

The aim of this study was to evaluate the usefulness of DNA flow cytometry to determine tumor nuclear DNA index (DI), and nucleolar organizer region protein counts visualized by the argyrophil (AgNOR) technique, in confirming diagnosis and predicting clinical outcome of patients with parathyroid carcinoma (PC). We reviewed paraffin-embedded tissue sections, from 15 patients (median age 63 years, range 30–68 years) with PC who died of the disease, which were randomly compared with tissue sections from 15 age- and sex-matched patients with parathyroid adenoma (PA). The proliferative activity in parathyroid tumours as detected by DI and AgNOR counts was evaluated in all specimens. Both DI (1.37 ± 0.33 vs 1.0 ± 0.1) and AgNOR (3.01 ± 0.31 vs 1.54 ± 0.35) counts were higher (P< 0.001) (Student’s t-test) in patients with PC than in those with PA. Diploid (DI = 1), aneuploid (DI>1) and hypoploid (DI<1) neoplasms were found in 11 (PC = 4, PA = 7), 14 (PC = 11, PA = 3) and five (PC = 0, PA = 5) patients respectively. The average postoperative survival in patients with PC was 46.9 ± 37.4 months (range 21–146 months). The survivals of patients with aneuploid (n= 11) and diploid (n= 4) PC were 74.0 ± 58.1 and 34.1 ± 18.4 months (P=0.21) respectively. There was a significant relationship between DI and AgNOR counts (R=0.69, P< 0.01), but no correlation was found between survival and both DI (Rho = 0.17, P= 0.55) and AgNOR counts (Rho = 0.26, P= 0.35). Moreover, there was no correlation (P= NS) between the main preoperative biochemical parameters and survival. In conclusion, DI and AgNOR are useful in confirming the diagnosis of PC, but they are of little value in predicting the clinical outcome of patients with PC.

High-fiber diet supplementation is commonly used in IBS, although it poses several management problems. Partially hydrolyzed guar gum (PHGG) has shown beneficial effects in animal and human studies, but its potential role in IBS symptom relief has not been evaluated yet. We investigated PHGG in IBS patients and compared it to a wheat bran diet. Abdominal pain, bowel habits, and subjective overall rating were longitudinally evaluated in 188 adult IBS patients (139 women and 49 men) for 12 weeks. Patients were classified as having diarrhea-predominant, constipation-predominant, or changeable bowel habits and were randomly assigned to groups receiving fiber (30 g/day of wheat bran) or PHGG (5 g/day). After four weeks, patients were allowed to switch group, depending on their subjective evaluation of their symptoms. Significantly more patients switched from fiber to PHGG (49.9%) than from PHGG to fiber (10.9%) at four weeks. Per protocol analysis showed that both fiber and PHGG were effective in improving pain and bowel habits, but no difference was found between the two groups. Conversely, intention-to-treat analysis showed a significantly greater success in the PHGG group (60%) than in the fiber group (40%). Moreover, significantly more patients in the PHGG group reported a greater subjective improvement than those in the Fiber group. In conclusion, improvements in core IBS symptoms (abdominal pain and bowel habits) were observed with both bran and PHGG, but the latter was better tolerated and preferred by patients, revealing a higher probability of success than bran and a lower probability of patients abandoning the prescribed regimen, suggesting that it can increase the benefits deriving from fiber intake in IBS, making it a valid option to consider for high-fiber diet supplementation.

Nitrosoureas constitute the main resource of chemotherapy for glioblastoma. However, because of chemoresistance, which is intrinsic or rapidly acquired after the first administration of chemotherapy, there have been few improvements in survival. Because O6-alkylguanine-DNA alkyltransferase (AGT) is the main target for increasing cell sensitivity to the nitrosoureas, we postulated that preexposure to other alkylating agents might increase the therapeutic index of the nitrosoureas by saturating all the copies of AGT present in the tumor cells.

OBJECTIVE: To evaluate the possible relationship between serum calcium, serum parathyroid hormone (PTH) levels and arterial blood pressure (BP) in patients with primary hyperparathyroidism (HPT). DESIGN: A retrospective population-based study. METHODS: Charts of 194 patients with proven primary HPT were reviewed, and the main clinical and biochemical parameters were recorded. There were 48 men (24.7%) and 146 women (75.3%), with a median age of 59 years (range 23-82 years). Patients who used antihypertensive drugs or hormone replacement therapy had been previously excluded. All patients underwent successful parathyroidectomy, and were cured of their disease. RESULTS: There were no differences (P=NS) between men and women in systolic (143.3+/-19.1 vs 145.4+/-17.1 mmHg) and diastolic (87.1+/-12.3 vs 88.4+/-9.9 mmHg) BP, and in the main biochemical parameters. A significant (P<0.01) correlation was found between (i) serum calcium and serum PTH levels (r=0.39, F=88.36), (ii) age and BP, both systolic (r=0.61, F=118.16) and diastolic (r=0.48, F=64.5), and (iii) body mass index (BMI) and BP (r=0.45 and 0.36 respectively). There was no significant association of serum calcium levels with systolic (r=0.0974, t=1.3422, P=0.18) or diastolic (r=0.1117, t=1.5409, P=0.12) BP, and of serum PTH levels with systolic (r=-0.0349, t=-0.4783, P=0.63) or diastolic (r=-0.0793, t=-1.0913, P=0.28) BP. Multivariate analysis confirmed that none of the independent biochemical parameters significantly correlated with BP, both systolic and diastolic. CONCLUSIONS: In patients with primary HPT there is no relationship between PTH, calcium and BP. Thus, in hyperparathyroid patients, BP should be considered as an independent variable, mainly related to age and BMI.

A series of 253 consecutive patients with proved primary hyperparathyroidism due to parathyroid tumours was reviewed. There were 68 (26.9%) men and 185 (73.1%) women, with a median age of 57 years (range 13-82 years). All patients, prior to successful parathyroidectomy, underwent one or more preoperative localization procedures such as: neck ultrasonography (US) in 191 (75.5%), (201)Tl/(99m)Tc-pertechnetate subtraction scintigraphy (TPS) in 144 (56.9%), CT scan in 92 (36.4%), (99m)Tc-sestamibi/(99m)Tc-pertechnetate subtraction scintigraphy (MPS) in 90 (35.6%), selective venous sampling (SVS) with parathyroid hormone (PTH) assay in 30 (11.9%), and magnetic resonance imaging (MRI) in 6 (2.4%) patients. The results were compared with operative and histological findings that showed 235 (92.9%) solitary parathyroid adenomas, 13 (5.1%) carcinomas and 5 (2.0%) double adenomas. Sensitivity and positive predictive value were 82.9% and 93.8% for US, 83.6% and 91.8% for TPS, 81.3% and 98.7% for CT scan, 85.1% and 96.1% for MPS, 65.4% and 80.9% for SVS, and 80.0% and 80.0% for MRI respectively. No different results (P=NS) were found using US, TPS, MPS or CT scan, whereas SVS and MRI sensitivity was lower (P<0.05). The combination of MPS and US was 94.0% sensitive (P<0.05) but when TPS, CT scan or MRI were also used overall sensitivity did not improve significantly (P=NS). In conclusion, MPS should be used as the starting preoperative localization procedure, while US and MPS together represent the most reliable noninvasive localization tool. If MPS and US are negative or not in agreement, further studies are not cost-effective and the patient should undergo bilateral neck exploration.

Abstract The present study evaluated the quality of life (QOL) of adult cirrhotic patients before orthotopic liver transplantation (OLT), the effect of OLT on QOL in the long-term and the effect of HCV recurrence within medical complications on QOL. Three groups of patients were studied: 19 pre-OLT, 33 during the first year post-OLT and 41 1 to 5 years post-OLT. The patients completed questionnaires on QOL and underwent liver function tests, immunosuppressive drug blood level determinations and medical complications evaluation. Somatization and depression and anxiety scores improved significantly during the first year post-OLT compared with pre-OLT, but they worsened again during the 1–5-year period post-OLT. Physical functioning and life satisfaction scores improved significantly during the first year post-OLT compared with pre-OLT and the improvement persisted 1–5-year during the period post-OLT. Patients with HCV recurrence compared with patients without HCV recurrence during the first year post-OLT showed a significant worsening of most of the domains of QOL. In conclusion, OLT improved most of the domains of QOL by the end of the first post-transplant year, though the improvements did not all persist in the long-term. Recurrence of HCV infection plays a major role in the impairment of QOL after OLT.

Given the current orientation towards the early treatment of stroke, this multicenter study was carried out in Northeast Italy in order to examine the times between stroke onset and hospital admission, and the possible factors leading to a lengthening of such times. An analysis was made of 348 patients, 79.8% of whom had experienced an ischemic cerebral infarct. Arrival times were not significantly modified by the distance from hospital, age, family cohabitation, socio-cultural level, population density or the geographical location of the Center. Sixty percent of the ischemic stroke cases arrived at the Emergency Department within three hours, and 80% within six hours; the hemorrhagic cases arrived earlier, 100% of them by the tenth hour. The duration of stay in the Emergency Department did not vary in relation to the severity or type of stroke. Greater severity, a reduced level of awareness and daytime onset led to a moderately significant reduction in presentation times. In conclusion, the majority of patients arrived sufficiently quickly to be treated within the “therapeutic window”; nevertheless, an information campaign may be useful in accelerating the hospital presentation of the albeit limited number of cases who arrive late.

Intracortical activity during recruiting responses (RRs) has been studied by recording laminar profiles of intracortical field potentials during repetitive stimulation, at 6 Hz, of nucleus centralis lateralis (CL) and nucleus centralis medialis (NCM) in lightly anesthetized cats, before and after topical application to the cortex of 1% GABA solution. The data obtained underwent current source density analysis (CSD) which disclosed that in the pre-GABA condition, there are two almost simultaneous sinks, one in the most superficial layer and the other in mid-cortical layers. After GABA application, a single large sink was present in mid-cortical layers. Extracellular single cortical unit activity was recorded in different animals, through a microelectrode tangentially inserted into the cortex, during repetitive stimulation of CL or NCM, both before and after GABA application. In 75% of these units there was, after GABA, a mean reduction of about 50% of firing probability while in the remaining 25% there was an increased activity. Topical application of 1% Manganese sulfate to the cortical surface appeared to completely inactivate the whole thickness of the cortex where it was applied, making evident the contribution to RRs of the potentials generated in the cortex buried in the adjacent sulci. Finally, a reciprocal facilitating effect of RRs and augmenting responses (ARs), which was studied by combined stimulation of nucleus ventralis posterolateralis (VPL) and NCM, appeared to be dependent upon an intracortical mechanism. All these data suggest that: 1) RRs are the result of a simultaneous activation of superficial and mid-cortical layers; 2) RRs are contaminated by a volume conducted potential arising from the cortex buried in the sulci; 3) a superficial inhibition following the initial excitation seems to be an usual component of the response; 4) ARs and RRs probably share a similar intracortical mechanism for incrementing the response.

Twenty-seven patients with myotonic dystrophy (MD) and 20 control subjects were tested using neuropsychological and electrophysiological measures. MD patients reported significantly lower scores on the Wechsler Adult Intelligence Scale and the Mini-Mental State Examination. P3 amplitude of auditory event-related potentials was significantly reduced in 14 patients. P3 latency was normal. In 13 patients, P3 was not elicited. Our results clearly show the presence of a significant impairment of cognitive functioning, as assessed by psychometric measures, in more than 50 of MD patients. Discriminant function correctly classified 92 of patients, using event-related potentials and neuropsychological variables.

Abstract: Alteration of the pharyngoesophageal musculature is a common finding in patients with myotonic dystrophy (MD), regardless of the presence of dysphagia. The aim of the present study was to determine whether a specific pattern of swallowing abnormalities could be identified in MD patients, and the possible correlation with the size of CTG repeats. Fifteen MD patients, 8 of whom were asymptomatic for dysphagia, underwent a videofluoroscopic study of swallowing. Alterations of the pharyngoesophageal phase of swallowing were detected in 12 of 15 patients, 6 without clinical evidence of dysphagia. Incomplete relaxation of the upper esophageal sphincter (UES) and esophageal hypotonia were the most common alterations. We found a significant correlation between the number of radiological alterations and the size of CTG repeats. A typical radiological pattern of swallowing has also been identified. The role of videofluoroscopy in evaluation of MD patients is briefly discussed.

The authors investigated the safety of 75 mg/m2temozolomide for 21 days every 28 days in glioma patients. This schedule could lead to DNA repair enzyme O6-alkylguanine-DNA alkyltransferase depletion, contributing to overcoming drug resistance. Although Phase III studies are forthcoming, no data are available on the long-term toxicity of temozolomide, which, in this series, incurred prolonged, cumulative lymphopenia, which leads to a high incidence of infections.

The authors prospectively followed 14 patients treated with thalidomide for cutaneous lupus erythematosus (CLE), in order to evaluate the occurrence of peripheral neuropathy (PN) and to assess whether PN correlates with thalidomide dose. The patients were followed for up to 24 months with neurologic and electrophysiologic evaluations. Seven patients (50) developed sensory axonal PN. The median time free from PN was 14 months. PN occurred after 10 months in the majority of patients. No correlations were found between thalidomide cumulative dose and occurrence of PN (Mann-Whitney U test; p> 0.16).