FLORENCE: a randomized, double-blind, phase III pivotal study of febuxostat versus allopurinol for the prevention of tumor lysis syndrome (TLS) in patients with hematologic malignancies at intermediate to high TLS risk.

BACKGROUND: Serum uric acid (sUA) control is of key relevance in tumor lysis syndrome (TLS) prevention as it correlates with both TLS and renal event risk. We sought to determine whether febuxostat fixed dose achieves a better sUA control than allopurinol while preserving renal function in TLS prevention. PATIENTS AND METHODS: Patients with hematologic malignancies at intermediate to high TLS risk grade were randomized to receive febuxostat or allopurinol, starting 2 days before induction chemotherapy, for 7-9 days. Study treatment was blinded, whereas daily dose (low/standard/high containing allopurinol 200/300/600 mg, respectively, or fixed febuxostat 120 mg) depended on the investigator's choice. The co-primary end points, sUA area under curve (AUC sUA1-8) and serum creatinine change, were assessed from baseline to day 8 and analyzed through analysis of covariance with two-sided overall significance level of 5%. Secondary end points included treatment responder rate, laboratory and clinical TLS incidence and safety. RESULTS: A total of 346 patients (82.1% intermediate TLS risk; 82.7% assigned to standard dose) were randomized. Mean AUC sUA1-8 was 514.0 ± 225.71 versus 708.0 ± 234.42 mgxh/dl (P < 0.0001) in favor of febuxostat. Mean serum creatinine change was -0.83 ± 26.98% and -4.92 ± 16.70% for febuxostat and allopurinol, respectively (P = 0.0903). No differences among secondary efficacy end points were detected. Drug-related adverse events occurred in 6.4% of patients in both arms. CONCLUSION: In the largest adult trial carried out in TLS prevention, febuxostat achieved a significant superior sUA control with one fixed dose in comparison to allopurinol with comparable renal function preservation and safety profile. CLINICAL TRIAL REGISTRATION: NCT01724528.

Open intensive care units: a regional survey about the beliefs and attitudes of healthcare professionals.

AIM: We aimed at assessing the opinion and degree of acceptance of physicians and nurses in Intensive Care Units (ICUs) toward an open ICU as our regional ethical committee has advised that ICU visitation policies be reformed using such a new approach. METHODS: This was a descriptive, cross-sectional, multicenter survey using the Beliefs and Attitudes toward Visitation in ICU Questionnaire mailed to the ICUs in our region. RESULTS: A total of 28 ICUs were invited, and 25 agreed to participate in this survey; 377 nurses and 230 physicians were surveyed with overall response rates of 94.9%% and 84.7%%, respectively. Nurses considered an open visiting policy to be an infringement on patient privacy (P<0.01), a possible interference with interactions between caregivers (P<0.01) and an impediment to their duties (P<0.05). They also significantly differed from physicians in considering open visitations a cause of more adverse hemodynamic events (P<0.05) and higher physiological and psychological stress for patients (P<0.05). With regard to attitudes, nurses strongly disagreed more frequently with the following: allowing everyone to visit the patient, accepting an open visitation policy in their unit, giving control of the visitation policy to the patient (P<0.01) and adapting visitation to the culture/ethnicity of the patients (P<0.0001). CONCLUSIONS: This study points out that, in our region, physicians are more liberal and able than nurses to "customize" their wards to the specific psychosocial and emotional needs of patients and visitors.

Devic's neuromyelitis optica and mitochondrial DNA mutation: a case report.

Cases are described with Leber's optic atrophy and neurological symptoms and/or MRI lesions suggestive of multiple sclerosis. We describe a case of a young woman with Devic's neuromyelitis optica and 3460 homoplasmic mitochondrial DNA mutation.

Differential diagnosis of acute myelopathies.

Diagnosis of acute myelopathy applies to subjects with acute motor involvement, segmental sensory loss and sphincter dysfunction, reaching a maximum no later than 4 weeks after onset. Among the different causes of acute myelopathy (e.g. compressive, vascular, traumatic or toxic lesions, paraneoplastic involvement and electrical injury), acute myelitis due to infective agents or to an autoimmune-inflammatory process frequently causes problems relating to the differential diagnosis of multiple sclerosis (MS) and its potential risk of developing MS.

Cranial nerve, brainstem and cerebellar syndromes in the differential diagnosis of multiple sclerosis.

A clinically isolated syndrome indicating a pathological process involving the cranial nerves or the posterior fossa may constitute a hard diagnostic challenge for the clinician. Whereas internuclear ophthalmoplegia, for example, is almost pathognomonic of multiple sclerosis (MS), other clinical presentations are often puzzling. The main alternative causes of symptoms that may suggest a clinical onset of MS are reviewed here, grouped in principal clinical syndromes, with particular attention to some rare, recently recognised conditions.

Validation of Italian multiple sclerosis quality of life 54 questionnaire.

OBJECTIVES: Health related quality of life (HRQOL) inventories are multi-dimensional measures of patient-centred health status developed for clinical research. The MS quality of life 54 (MSQOL-54) is an MS-specific HRQOL inventory originally devised for English speaking patients. It consists of a core measure, the 36-item short form health survey (SF-36) previously adapted into Italian, and 18 additional items exploring domains relevant to patients with MS (MS-18 module). The authors translated and culturally adapted into Italian the MS-18 module of the MSQOL-54 questionnaire, and clinically validated the whole questionnaire. METHODS: The MS-18 module was translated following the methodology of the International Quality of Life Assessment (IQOLA) project. The MSQOL-54 was validated in 204 consecutive patients with MS seen between April and September 1997 at three participating centres. The questionnaire was explained by the physician who also administered the expanded disability status scale (EDSS) and mini mental status scale examination, and the patient filled in the MSQOL-54 and Beck depression inventory questionnaires (BDI), with assistance if required. The contribution of impairments and disabilities to MSQOL-54 scores were assessed, and mean scores were compared with normative data for the general Italian population, and with the original sample of United States MS patients. RESULTS: The mean age of the 204 patients was 42 years; mean EDSS score was 4.5 (range 0-8. 5). Patients' participation in the assessment was satisfactory, and all scales satisfied the usual psychometric standards. The characteristics of the United States sample matched those of our patients in all but gender (72% United States patients v 52% Italian patients were women), and education (90% United States patients and 44% Italian patients completed high school); MSQOL-54 profiles were also similar. The EDSS was significantly associated with the physical health composite but not with the mental health composite score. Multiple linear regression modelling showed that age and BDI independently predicted physical health composite (p < 0.001), and mental health composite (p < 0.001). Clinical worsening in the previous year had an independent effect on the physical health composite (p < 0.001). CONCLUSIONS: The Italian version of MSQOL-54 is easy to administer and is well accepted by patients. Neurological impairment has a limited influence on perceived quality of life, while age and depressive symptoms has a major influence.

A simple method for recording motor evoked potentials of lingual muscles to transcranial magnetic and peripheral electrical stimulation.

Motor evoked potentials were recorded from lingual muscles by means of clip electrodes applied on the lateral side of the tongue, following transcranial magnetic stimulation and peripheral electrical stimulation of the 12th cranial nerve at the mandible jaw. Using a circular coil, the stimulation of the cerebral cortex elicited a response of about 8 ms: its amplitude was higher in the right tongue placing the coil over the contralateral hemisphere, 4 cm from the vertex, with coil currents flowing counterclockwise. Coil position and current flow direction did not significantly modify the characteristics of responses recorded from the left side. The separate stimulation of either hemisphere was better obtained using an 8-shaped coil. The latency of the motor response measured 7.7-8.0 ms, the amplitude was greater on stimulation of the contralateral than the ipsilateral hemisphere and was larger recording from the right (3.3 +/- 1.1 mV) than from the left (1.2 +/- 0.7 mV) side. Positioning the circular coil over the parieto-occipital skull, a response of 4.1 +/- 0.3 ms was obtained, reflecting the intracranial activation of the hypoglossal nerve. The peripheral stimulation at the mandible elicited a response of 3.2 +/- 0.5 ms. The method described appears simple and reliable, potentially helpful in clinical practice.

[Echo-Doppler in chronic kidney transplant rejection. The diagnostic prospects using indices of the ascending systolic phase]. / L'eco Doppler nel rigetto cronico del rene trapiantato. Prospettive diagnostiche mediante indici di fase ascendente sistolica.

To date, Doppler US has been rarely used to diagnose chronic renal transplant rejection because of its low sensitivity. Nevertheless, all the results have been obtained from the analysis of flow-metric indices, mainly considering the diastolic phase of the Doppler waveform, e.g., the resistance index (RI) and the pulsatility index (PI). This study was aimed at investigating if Doppler diagnostic accuracy in renal transplant monitoring can be increased by studying the systolic phase, considering peak arterial systolic velocity (Vp), acceleration time (AT) and acceleration index (AI). Seventy-six renal transplant recipients were examined with color-Doppler and duplex Doppler US, which showed 47 well-functioning and 29 hypofunctioning kidneys. The diagnosis was confirmed with perfusion scintigraphy with 99mTc DTPA, biopsy and 6-month clinical-laboratory follow-up. The means of Vp, AI, AT and RI relative to the group of patients with normal renal function were compared with those in the group of patients with chronic rejection. Critical values were measured at the segmental arteries (Vp = 70 cm/s, AI = 7 m/s2, AT = 100 ms), at the interlobar arteries (Vp = 45 cm/s, AI = 4 m/s2, AT = 100 ms) and at the arcuate arteries (Vp = 35 cm/s, AI = 3 m/s2, AT = 100 ms). On the basis of these values, normal functioning transplants were differentiated from hypofunctioning ones. RIs were altered (> 0.75) in 8 of 17 chronic rejections and in 3 of 47 normal transplants, with 47.1% sensitivity and 93.6% specificity. The combination of RI with Vp and AI strongly increased both sensitivity (100%) and specificity (82.98%). Combined AI and RI exhibited 94.1% sensitivity and 89.3% specificity. In conclusion, the indices of the ascending systolic phase, in peripheral vascular samplings, are clearly more efficacious than RI alone and index combination exhibits the highest diagnostic accuracy.

In vitro cytokine, sCD23 and IgG secretion in multiple sclerosis.

Synthesis of IgG by peripheral blood mononuclear cells from patients with multiple sclerosis (MS) and with other neurological diseases and from healthy controls was induced by Pokeweed mitogen (PWM) in short-term cultures. As expected, MS patients produced more immunoglobulin (Ig) G and had a higher percentage of 'high responders' to PWM stimulation as compared to controls. Interleukin (IL)-4 was undetectable in all samples. IL-6 and tumor necrosis factor (TNF)-alpha synthesis was induced by PWM stimulation in all groups, but MS patients showed the most significant increase of both cytokines. Interestingly, only MS patients showed a significant increase of the soluble form of CD23 receptor (sCD23). Moreover, only sCD23 levels correlated with in vitro IgG production in MS patients. The levels of IL-6, TNF-alpha, sCD23 were greater in high responders compared to low responders in all groups. The mean value of each molecule, however, did not differ significantly among overall groups. A highly significant difference was reported for sCD23 in MS patients. We suggest that sCD23, also known as B cell growth factor, may play a role in the well-documented phenomenon of in vitro IgG hypersynthesis in MS patients, adding support to the concept of B cell up-regulation in the peripheral blood of these patients.

[Utility of electrophysiologic study using the blink reflex and brainstem evoked potentials for the evaluation of the course of uremic polyneuropathy]. / Utilità dello studio elettrofisiologico mediante blink reflex e potenziali evocati del tronco encefalico (BAEPS), per la valutazione dell'evoluzione della polineuropatia uremica.

On the present study the authors evaluate the utility of electrophysiologic examination in uraemic polyneuropathy. A group of 19 uraemic patients in chronic dialysis underwent the Blink reflex and BAEPSs study to evaluate the alterations of nervous pathways. The results obtained were compared with those of a group of 10 healthy patients comparable for age and sex. The electrophysiologic parameters have been statistically compared with the plasma levels of vit. B12. folic acid, PTH and beta-2-microglobulin. The results show a significant difference of uremic patients compared with the healthy ones for the Blink reflex (ipsilateral and contralateral R2 responses). Also BAEPSs show significant alterations in the uraemic group (latencies of the III, V components). A statistically significantly inverse correlation is present between folic acid values and blink reflex R1 and R2 responses. Therefore our study shows the existence of a combined degeneration of central and peripheral nervous pathways in chronic uraemic patients. We believe that the decrease in folic acid concentration found in our study may be one of the causes of the beginning and then of the worsening of neurologic damage.

Erectile impotence in multiple sclerosis: a neurophysiological study.

Pudendal evoked potentials, motor evoked potentials of the bulbocavernosus muscle to magnetic stimulation and bulbocavernosus reflex were recorded in 34 patients with multiple sclerosis (MS). Responses were delayed in 26, 20 and 3 cases respectively. No relationship was found between neurophysiological abnormalities and the presence or severity of erectile dysfunction, showing that these tests have little diagnostic usefulness in MS patients with impotence. Nocturnal penile tumescence was assessed in 14 cases: the test result was normal in 10 patients, including 3 severely paraplegic subjects.

[Frequency of hereditary neurologic diseases. A clinical study]. / La frequenza delle malattie neurologiche ereditarie. Uno studio clinico.

INTRODUCTION: The nervous system is affected in 30% of hereditary monogenic disorders and as many as 500 single-gene disorders display major neurologic symptoms. We have studied the frequency of hereditary neurological diseases to assess their importance in daily hospital activity. Only single-gene hereditary diseases with central or peripheral nervous system involvement were considered; thus chromosomal diseases and diseases with multifactorial etiology were excluded. METHODS: We surveyed admission to in- and out-patient departments of Neurology, Pediatrics, and Dermatology of the Aosta Regional Hospital for the calendar years 1982-1991, collecting 229 cases, 95 women and 134 men. Out-patient departments held 126 patients, the others came from in-patient departments. Admission to the neurological in-patient department were 1.8% of total neurological admissions in the same period. Each diagnosis was assigned to the code number of the International Classification of Diseases (ICD-IX Revision, 1975). RESULTS: We found 33 different phenotypes. Most frequent diagnoses were: essential tremor (89 patients), hereditary sensory-motor neuropathy (HSMN) type I (28), Huntington's chorea (13), progressive muscular dystrophy limb-girdle type (8), neurofibromatosis type I (9), HSMN type II (9), spinocerebellar ataxia (9), hereditary spastic paraplegia (7), spinal muscular atrophy type IV (5), myotonic dystrophy (5), cerebellar ataxia (4), HSMN type III (4), spinal muscular atrophy type II and III (3), tuberous sclerosis (3). Essential tremor mostly affected persons in the over-50 age groups. On the contrary, the other neurologic monogenic diseases were diagnosed in all ages with the following age-group breakdown: 0-9, 11%; 10-19, 16%; 20-29, 15%; 30-39, 8%; 40-49, 11%; 50-59, 19%; 60-69, 14%, 70+, 7%. Consistently with the general rule, autosomic recessive diseases have the earliest onset and autosomic dominant ones the latest; HSMN, spinal muscular atrophy and Huntington's chorea were the disorders diagnosed in older age group. DISCUSSION: Although the frequency of the single neurologic monogenic disease is low (with the exception of essential tremor), their overall prevalence is higher than the prevalence of multiple sclerosis or the peripheral neuropathies. All age-groups are involved. We separated three groups of diseases: 1) two relatively benign diseases, essential tremor and the HSMN, affecting half of our patients; 2) five severe and more common diseases (Huntington's chorea, progressive muscular dystrophy limb-girdle type, neurofibromatosis type I, spinocerebellar ataxia, hereditary spastic paraplegia), affecting 1/4 of patients; and 3) a group of rare, mostly severe diseases, affecting the remaining 1/4 of patients.

Clinical and neuroradiological findings in a case of pure word deafness.

Pure Word Deafness is a clinical syndrome included among the aphasias and is marked by complete deafness of sudden onset with conserved ability to understand and read the written word and with no speech disorders. We report the case of 61 year old man in whom pure word deafness developed after two episodes of acute cerebral ischemia in quick succession. Neuroimaging procedures, that is: computed tomography scan, single photon emission computed tomography and magnetic resonance imaging, revealed the presence of two ischemic lesions in the temporal cortex bilaterally. Neurophysiological investigations (electroencephalogram, brainstem auditory evoked potentials and stapedial reflex) were also studied. We discuss the outcome of all these investigations in the light of the relevant published work.

Follow-up of nerve conduction in chronic uremic patients during hemodialysis.

We studied to evolution of nerve conduction during hemodialysis following 21 patients with chronic renal failure. Mean motor nerve conduction velocity (MCV) was significantly different at hemodialysis onset and 3 years later for both common peroneal nerve (44.5 and 41.0 m./sec.) and ulnar nerve (52.5 and 47.1 m./sec.). MCV decreased more in patients with low Kt/V (a depuration index) than in those with high Kt/V.

[Clinical evaluation of 12 months of biofiltration in an elderly group]. / Valutazione clinica su 12 mesi di biofiltrazione in un gruppo di anziani.

Biofiltration (BF) was performed on 8 elderly uraemic patients (mean age 73.75 +/- 8.72 years; dialytic age 75.00 +/- 38.42 months) to improve cardiovascular stability and to reduce the dialytic session time. Small molecules (nitrogen, creatinine, uric acid, phosphorus) depuration, heamogasanalysis and PA monitoring, were compared against previous datum obtained by the same group that had undergoing acetate dialysis (AC. HD) for a year. Small molecules showed no significant differences; in BF the incidence of symptomatic hypotensions and the dialytic session time were reduced (30% and 30 min. respectively), with a better metabolic acidosis correction versus AC.HD. Our results showed that BF is better than AC.HD in elderly uraemic patients.

[Hemo-rheologic changes following treatment with human recombinant erythropoietin in chronic hemodialysis patients]. / Alterazioni emoreologiche in seguito a trattamento con eritropoietina umana ricombinante in pazienti emodializzati cronici.

Human recombinant erythropoietin constitutes a remarkable improvement in the treatment of uraemic anemia. Nevertheless, it causes haemorheological changes, which in turn may affect smaller blood vessel circulation. Our study was conducted on a pool of chronic uraemic patients under hemodialytic treatment who were given erythropoietin therapy. Substantial increases in overall blood viscosity and red cell aggregation were recorded, with no change in erythrocyte deformation. An increase in cardiovascular morbidity might occur in these patients who are already liable to this condition. Several years will have to elapse and thorough studies will have to be conducted on a large number of patients, to have conclusive evidence on this point.

Peripheral neuropathy caused by antiepileptic drugs. Neurophysiological study of the A delta and C fibers.

The risk that antiepileptic drugs may cause damage to the peripheral nervous system led us to investigate 12 patients on carbamazepine and 12 patients on phenobarbital with the thermal threshold test. The heat and cold thresholds were measured at the ankle and wrist and, compared with those in 30 healthy subjects, they proved to be significantly higher. When the two groups of epileptics were compared separately with the controls, their thresholds were always higher. These findings are consistent with a toxic effect of both drugs on fine peripheral nerve fibers.

Use of immunomodulators (thymopentine) in hepatitis B vaccine in elderly patients undergoing chronic hemodialysis.

Thymopentine is a synthetic immunomodulator that positively affects T-lymphocyte maturation, reproduction and differentiation. In elderly uremic patients nonresponders to hepatitis B vaccine, the administration of this drug has been shown to improve the response to the new vaccination.