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Biomedical subjects

A Quattrone

Publications and source records attributed to A Quattrone.

At least 109 records · Page 6Linked to original sources
PubMed1998

Genetic heterogeneity in autosomal recessive hereditary motor and sensory neuropathy with focally folded myelin sheaths (CMT4B).

Hereditary motor and sensory neuropathy with focally folded myelin sheaths, or Charcot-Marie-Tooth disease neuropathy type 4B (CMT4B), is a distinct clinical and genetic entity belonging to the heterogeneous group of autosomal recessive demyelinating neuropathies. We previously described a large pedigree with CMT4B and found evidence of linkage to chromosome 11q23. We now describe a second, unrelated family in which two individuals were affected with CMT4B. We exclude the disease locus segregating in this smaller pedigree from the 11q23 region as well as from most of the regions where other CMT loci have been mapped. We thus provide evidence for a second locus causing the CMT4B phenotype.

Adult↗
PubMed1998

Randomized trial comparing two different high doses of methylprednisolone in MS: a clinical and MRI study.

OBJECTIVE: To assess the efficacy of two different high doses of intravenous methylprednisolone (IVMP) for the treatment of relapses in MS. BACKGROUND: IVMP is the treatment of choice for MS relapses, but it is unknown whether its effects are dose related. METHODS: We conducted a double-blind, randomized study. Follow-up included serial clinical and MRI recordings at baseline and at 7, 15, 30, and 60 days after the beginning of treatment. Outcome measures were the number of brain and cervical spinal cord MRI contrast-enhancing lesions, and the Expanded Disability Status Scale score. RESULTS: Both treatment regimens improved clinical scores and reduced the number of MRI enhancing lesions during the follow-up period. The higher dose of IVMP was significantly more effective than the lower dose in reducing the number of MRI contrast-enhanced lesions at 30 and 60 days, mainly by decreasing the rate of new lesion formation. CONCLUSIONS: The higher dosage of IVMP has a more powerful and prolonged action in maintaining blood-brain barrier integrity after a clinical relapse.

Adult↗
PubMed1998

Kufs' disease presenting as late-onset epilepsia partialis continua.

A 64-year-old woman, who had no personal or family history of neurologic diseases, had an 18-month history of epilepsia partialis continua (EPC) associated with a moderate intellectual deterioration and subtle extrapyramidal rigidity. There was no photosensitive response. A thorough laboratory investigation was unremarkable. A biopsy of the rectal mucosa revealed abundant fingerprint profiles diagnostic of Kufs' disease (KD). Our case expands the clinical picture of KD and suggests that such a diagnosis should be considered in adult-onset EPC.

Age of Onset↗
PubMed1997

The antisense bcl-2-IgH transcript is an optimal target for synthetic oligonucleotides.

In most human follicular B cell lymphomas the bcl-2 gene is up-regulated as a result of the t(14;18) chromosomal translocation generating a hybrid bcl-2-IgH mRNA. Recently, we have identified in t(14;18)-positive cells a bcl-2-IgH mRNA in the antisense orientation, putatively responsible for the overexpression of bcl-2. Herein we show that this chimeric antisense transcript is an optimal target for synthetic oligodeoxynucleotides (ODNs). A variety of sense-oriented oligonucleotides have been designed that target the antisense transcript in regions endowed with a sequence specificity presumably restricted to an individual cell line (the bcl-2-IgH fusion regions) or extended to all t(14;18) cells (the ectopic bcl-2 segment upstream from the major breakpoint region and the IgH segment). All sense-oriented ODNs complementary to the antisense transcript induced an early strong inhibition of cell growth and a late fulminant cell death. As expected, the activity of ODNs targeting the fusion region was restricted to each individual cell line, whereas the activity of all ODNs targeting the common bcl-2 and IgH segments was extended to all t(14;18) cell lines tested. These sense ODNs were not effective in untranslocated cell lines. Antisense-oriented ODNs, complementary to the bcl-2-IgH mRNA, and control ODNs (scrambled, inverted, or mismatched) were biologically ineffective. The selectivity and efficacy of all sense ODNs tested provide support for the development of therapeutic ODNs targeting the bcl-2-IgH antisense transcript expressed in human follicular lymphomas.

Apoptosis↗
PubMed1997

Blockade of clomipramine and amitriptyline analgesia by an antisense oligonucleotide to mKv1.1, a mouse Shaker-like K+ channel.

The effect of an antisense oligonucleotide to the K+ channel coding mKv1.1 mRNA on antinociception induced by the tricyclic antidepressants, clomipramine (20-35 mg kg(-1) s.c.) and amitriptyline (10-25 mg kg(-1) s.c.), was investigated in the mouse hot-plate test. Antisense oligonucleotide (0.5-1.0-2.0-3.0 nmol per i.c.v. injection) produced a dose-dependent inhibition of clomipramine and amitriptyline antinociception 72 h after the last i.c.v. injection. The sensitivity to both analgesic drugs returned 7 days after antisense oligonucleotide injection, indicating the absence of irreversible damage or toxicity. Treatment with a degenerated oligonucleotide did not modify the clomipramine- and amitriptyline-induced antinociception in comparison with that in naive (unpretreated controls), vector and saline i.c.v.-injected mice. A quantitative reverse transcription-polymerase chain reaction (RT-PCR) study demonstrated a reduction in mRNA levels only in the antisense oligonucleotide treated group. Antisense oligonucleotide, degenerated oligonucleotide or vector pretreatment, in the range of doses used, did not produce any behavioural impairment as revealed by the mouse rotarod and hole-board tests. The present results indicate that modulation of the mKv1.1 K+ channel plays an important role in the central analgesia induced by the tricyclic antidepressants, clomipramine and amitriptyline.

Amitriptyline↗
PubMed1997

Effect of K+ channel modulation on mouse feeding behaviour.

The K+ channel antagonists, glucose (100 microg per mouse i.c.v.), tetraethylammonium (1 microg per mouse i.c.v.) and apamin (1 ng per mouse i.c.v.), reduced food intake of mice comparably to the two anorectic drugs, amphetamine (10 microg per mouse i.c.v.) and cocaine (50 microg per mouse i.c.v.). Conversely, the K+ channel openers, minoxidil (5 microg per mouse i.c.v.) and pinacidil (10 microg per mouse i.c.v.), elicited an orectic effect of the same intensity as that induced by 2-deoxyglucose (200 microg per mouse i.c.v.), aurothioglucose (200 microg per mouse i.c.v.) and neuropeptide Y (0.5 microg per mouse i.c.v.). The antisense oligodeoxyribonucleotide (1-3 nmol per injection) to mKv1.1 gene produced, at 72 h, a dose-dependent increase in food intake. A quantitative reverse transcription-polymerase chain reaction (RT-PCR) study demonstrated a reduction in cerebral mRNA levels only in the antisense oligodeoxyribonucleotide-treated group, indicating the absence of a sequence-independent action. Mice receiving the K+ channel modulators or antisense oligodeoxyribonucleotide had unmodified motor coordination and inspection activity as revealed, respectively, by the rotarod and hole-board tests. The integrity and functionality of central K+ channels appears, therefore, to be fundamental in the regulation of food intake by mice.

Amphetamine↗
PubMed1997

Reversible antisense inhibition of Shaker-like Kv1.1 potassium channel expression impairs associative memory in mouse and rat.

Long-term memory is thought to be subserved by functional remodeling of neuronal circuits. Changes in the weights of existing synapses in networks might depend on voltage-gated potassium currents. We therefore studied the physiological role of potassium channels in memory, concentrating on the Shaker-like Kv1.1, a late rectifying potassium channel that is highly localized within dendrites of hippocampal CA3 pyramidal and dentate gyrus granular cells. Repeated intracerebroventricular injection of antisense oligodeoxyribonucleotide to Kv1.1 reduces expression of its particular intracellular mRNA target, decreases late rectifying K+ current(s) in dentate granule cells, and impairs memory but not other motor or sensory behaviors, in two different learning paradigms, mouse passive avoidance and rat spatial memory. The latter, hippocampal-dependent memory loss occurred in the absence of long-term potentiation changes recorded both from the dentate gyrus or CA1. The specificity of the reversible antisense targeting of mRNA in adult animal brains may avoid irreversible developmental and genetic background effects that accompany transgenic "knockouts".

Animals↗
PubMed1997

Long-duration response to levodopa influences the pharmacodynamics of short-duration response in Parkinson's disease.

The long-duration response (LDR) to chronic levodopa treatment may mask the short-duration response (SDR) to a single dose of the drug in Parkinson's disease (PD). As a result, the measurement of SDR may be inaccurate for establishing levodopa dosing regimen in individual patients. To evaluate the possible contamination of SDR by LDR, we investigated in 16 patients with PD the characteristics of SDR to a single dose of levodopa administered after a prolonged washout from chronic therapy and after a 15-day treatment period with levodopa. Levodopa treatment produced a sustained LDR, and the SDR, measured on the 15th day of treatment, had lower magnitude and shorter duration than the response recorded after washout. Moreover, after treatment, SDR did not vary between patients with mild and severe PD, whereas, after washout, severely affected patients had larger but shorter SDR than mildly affected patients. The evaluation of SDR without the interference of LDR is critical in defining the characteristics of the therapeutic response to levodopa.

Administration, Oral↗
PubMed1997

Short-term levodopa test assessed by movement time accurately predicts dopaminergic responsiveness in Parkinson's disease.

Short-term challenges with dopaminergic agents are used in patients with idiopathic Parkinson's disease (PD) to predict the therapeutic effect of sustained levodopa treatment, but false-negative results often occur. We prospectively evaluated 74 patients with clinically diagnosed IPD and compared the predictive value of a short-term levodopa test assessed by movement time (MT) with the predictive value obtained by the evaluation with the motor examination part of the Unified Parkinson's Disease Rating Scale (UPDRS-ME). The response to long-term levodopa was accurately predicted in 96% of patients by assessing the response to the short-term test with MT and in 80% of cases with UPDRS-ME. Similar predictive values were obtained by separately analyzing 21 de novo patients. The short-term test also accurately predicted the magnitude of improvement with long-term treatment. We conclude that the predictive value for long-term dopaminergic responsiveness may be further enhanced by evaluating the short-term pharmacologic challenges with MT analysis. This is particularly useful to select de novo patients for drug trials with dopaminergic agents.

Aged↗
PubMed1997

Action palatal tremor in a patient with primary intestinal lymphoma.

We report the case of a 59-year-old man with primary intestinal T-cell non-Hodgkin's lymphoma who developed abnormal facial twitching synchronous with small palatal movements induced by attempts at speaking or swallowing. At rest, the electromyogram (EMG) showed no spontaneous muscular activity. Phonation triggered trains of synchronous, rhythmic EMG bursts at a frequency of 3-4 Hz lasting 10-20 s, with an average burst of 150 ms, which simultaneously involved palatal, facial, and neck muscles bilaterally with left-sided predominance. An enhanced blink reflex recovery curve was observed after stimulation of either side. Backaveraging electroencephalographic study revealed no activity that was time locked with the jerks. Axial T2-weighted magnetic resonance imaging showed an increased signal intensity and bilateral enlargement of the inferior olives. No antineuronal-specific antibodies were found in the blood or in the cerebrospinal fluid. All of these clinical findings were consistent with a symptomatic palatal tremor (PT). Because it was triggered by activation of cranial muscles, we termed this movement disorder action PT. To our knowledge, this is the first report of symptomatic PT displaying these features.

Blinking↗
PubMed1997

A phase II study of interferon alpha and low-dose subcutaneous interleukin-2 in advanced renal cell carcinoma.

The activity of the drugs employed in the treatment of metastatic renal cell carcinoma, including biological response modifiers, is limited; one of the aims of clinical research in this area is to maintain the benefits of treatment whilst reducing its toxicity to a minimum level. We have evaluated toxicity and response of the combined administration of recombinant interferon alpha (IFN alpha) and low-dose subcutaneous (s.c.) recombinant interleukin-2 (IL-2) in patients with advanced renal cell carcinoma. A group of 20 previously untreated patients with advanced renal cell carcinoma were included in the study. Treatment consisted of 3 MU/m2 recombinant IFN alpha daily i.m. continuously, and 0.5 MU/m2 recombinant IL-2 twice a day s.c. on days 1-5 for the first week, followed by 1 MU/m2 twice a day for 5 days in the following weeks. For IL-2, a 1-week rest was allowed after 4 weeks of treatment. Response was assessed after 3 months of therapy. Three objective responses were seen, one complete and two partial. Eight patients had stable disease. The median time to progression was 6 months; the median survival for all patients was 14 months. Side-effects were low, limited to grades 1 and 2 in the majority of patients, and included fever, anemia, leukopenia, dyspnea, and abnormalities of liver and renal function tests. Any flu-like syndrome was judged moderate in most patients; however, one-third of the patients refused treatment mostly because of the flu-like syndrome. One of these was the patient experiencing a complete response, who virtually received IFN alpha alone. This regimen, similar to others employed in the treatment of advanced renal cell carcinoma, produced a 15% response rate (95% confidence interval, 0-31%) with 14 months median survival, moderate toxicity and low cost, and required no hospitalization. These data seem to indicate an effectiveness comparable to, and a toxicity lower than, that of regimens employing higher doses of IL-2.

Adult↗
PubMed1997

Vitamin E protects human skeletal muscle from damage during surgical ischemia-reperfusion.

PURPOSE: The biochemical and morphological alterations induced in lower limb skeletal muscle by ischemia-reperfusion (I-R) during aortic surgery and the effect of vitamin E pretreatment were investigated. METHODS: Two groups of patients undergoing aortic aneurysm resection, one untreated and one treated with vitamin E, were examined. Quadricep muscle biopsies were taken after induction of anesthesia, at the end of ischemia, and after reperfusion. The malondialdehyde (MDA) content and morphology of biopsies were examined to assess peroxidative processes. RESULTS: Ischemia did not induce an increase in MDA content but did increase neutrophil infiltration in muscle fibers of untreated patients. Reperfusion led to a significant increase in MDA content and to intermyofibrillar edema and mitochondrial swelling. The MDA content was not increased during ischemia and neutrophil infiltration was minimal in vitamin E treated patients. At reperfusion, the MDA content, the ultrastructural injuries and neutrophil infiltration were significantly reduced by the treatment. CONCLUSIONS: Vitamin E is effective in reducing the oxidative muscle damage occurring after a period of I-R.

Aged↗
PubMed1997

Spontaneous remission of childhood epilepsy in two patients with focal extraopercular cortical dysplasia.

Childhood-onset partial epilepsy caused by focal cortical dysplastic lesions (FCDLs) is often severe. A few patients reported with a favorable outcome had a normal neuropsychological examination, and FCDLs were always localized around the opercular region, suggesting that extent and location of the lesion may account for the favorable outcome. We report two patients with extraopercular FCDLs, who had a spontaneous remission of their childhood-onset epilepsy, despite a severe neurological deficit. A 22-year-old girl (patient 1) and a 16-year-old boy (patient 2), began to have partial seizures at the age of 9 years and 1 year respectively. On neurological examination, patient 1 had left hemiparesis and patient 2 had low IQ. Interictal EEG recordings revealed repetitive epileptiform discharges involving the right temporo-parietal or frontal areas in patients 1 and 2 respectively. MRI study showed focal cortical thickening or abnormal gyration located over the right parietal and frontal region respectively in patients 1 and 2, but failed to evidence T2 prolongation in the white matter beneath the dysplastic cortex. Optimal antiepileptic regimen always stopped seizures. Their long-term course was favorable, with remission of the seizures and normalization of EEG recordings, even 4-5 years after medication withdrawal. In conclusion, FCDLs may cause epilepsy with a benign course even in patient with mental retardation or neurological abnormalities. This may be related to a morphologically milder dysplastic lesion than found in patients with FCDLs and severe epilepsy.

Adolescent↗
PubMed1997

Disappearance of periodic sharp wave complexes in Creutzfeldt-Jakob disease.

Periodic sharp wave complexes (PSWC) are sensitive and specific of Creutzfeldt-Jakob disease (CJD). Once they have emerged, PSWC may exceptionally disappear in the terminal stage of the disease, as a consequence of the flattening of scalp electroencephalogram (EEG). We document the disappearance of PSWC in serial EEG during the clinical course in two women (57 and 70 years of age) with pathologically proven CJD. Despite PSWC disappearance, diffuse theta-delta activity was still well recognizable. Moreover, external stimuli failed to trigger PSWC. The absence of PSWC in CJD might be due to the timing and frequency of EEG recordings. PSWC disappearance should not be interpretated as evidence against the diagnosis of CJD.

Aged↗
PubMed1997

Negative myoclonic status due to antiepileptic drug tapering: report of three cases.

PURPOSE: Epileptic negative myoclonus (ENM) has been increasingly recognized in different epilepsies, but the reasons for its appearance and prognosis remain uncertain. We report 3 patients who developed de novo, almost continuous ENM, triggered by antiepileptic drug (AED) tapering, that resolved with treatment. METHODS: Three patients aged 16, 19, and 65 years with a 13- to 36-year history of partial epilepsy were receiving a therapeutic dosage of carbamazepine or phenobarbital plus either clobazam (CLB) or valproate (VPA). None had previously had ENM. Forty-eight to 72 h after CLB or VPA withdrawal, the habitual seizures recurred. The patient also began to report repetitive postural lapses of one or more limbs that interfered with eating or writing. At this time, each patient underwent polygraphy with simultaneous surface electromyography (EMG) of deltoid, biceps, and triceps muscles and of the wrist extensor and flexor bilaterally. RESULTS: In all patients, EEGs demonstrated almost continuous epileptiform discharges whose spatial distribution was similar to that observed before ENM appearance. Polygraphic recordings showed repetitive loss of postural EMG activity in one or more limbs, 100-400 ms in duration, which occurred in conjunction with the spike-waves. One milligram of clonazepam intravenously always terminated ENM status, which has not recurred in the ensuing 9-36 months. CONCLUSIONS: ENM may emerge as a new type of seizure due to tapering of AED therapy. This effect is possibly related to the great activation of epileptiform activity with consequent interference with cortical activity.

Adolescent↗