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M Gaviria

Publications and source records attributed to M Gaviria.

At least 19 recordsLinked to original sources
PubMed2006

Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel: spontaneous recovery after spinal cord injury and statistical power needed for therapeutic clinical trials.

The International Campaign for Cures of Spinal Cord Injury Paralysis (ICCP) supported an international panel tasked with reviewing the methodology for clinical trials in spinal cord injury (SCI), and making recommendations on the conduct of future trials. This is the first of four papers. Here, we examine the spontaneous rate of recovery after SCI and resulting consequences for achieving statistically significant results in clinical trials. We have reanalysed data from the Sygen trial to provide some of this information. Almost all people living with SCI show some recovery of motor function below the initial spinal injury level. While the spontaneous recovery of motor function in patients with motor-complete SCI is fairly limited and predictable, recovery in incomplete SCI patients (American spinal injury Association impairment scale (AIS) C and AIS D) is both more substantial and highly variable. With motor complete lesions (AIS A/AIS B) the majority of functional return is within the zone of partial preservation, and may be sufficient to reclassify the injury level to a lower spinal level. The vast majority of recovery occurs in the first 3 months, but a small amount can persist for up to 18 months or longer. Some sensory recovery occurs after SCI, on roughly the same time course as motor recovery. Based on previous data of the magnitude of spontaneous recovery after SCI, as measured by changes in ASIA motor scores, power calculations suggest that the number of subjects required to achieve a significant result from a trial declines considerably as the start of the study is delayed after SCI. Trials of treatments that are most efficacious when given soon after injury will therefore, require larger patient numbers than trials of treatments that are effective at later time points. As AIS B patients show greater spontaneous recovery than AIS A patients, the number of AIS A patients requiring to be enrolled into a trial is lower. This factor will have to be balanced against the possibility that some treatments will be more effective in incomplete patients. Trials involving motor incomplete SCI patients, or trials where an accurate assessment of AIS grade cannot be made before the start of the trial, will require large subject numbers and/or better objective assessment methods.

Clinical Trials as Topic↗
PubMed2006

Guidelines for the conduct of clinical trials for spinal cord injury (SCI) as developed by the ICCP panel: clinical trial outcome measures.

An international panel reviewed the methodology for clinical trials of spinal cord injury (SCI), and provided recommendations for the valid conduct of future trials. This is the second of four papers. It examines clinical trial end points that have been used previously, reviews alternative outcome tools and identifies unmet needs for demonstrating the efficacy of an experimental intervention after SCI. The panel focused on outcome measures that are relevant to clinical trials of experimental cell-based and pharmaceutical drug treatments. Outcome measures are of three main classes: (1) those that provide an anatomical or neurological assessment for the connectivity of the spinal cord, (2) those that categorize a subject's functional ability to engage in activities of daily living, and (3) those that measure an individual's quality of life (QoL). The American Spinal Injury Association impairment scale forms the standard basis for measuring neurologic outcomes. Various electrophysiological measures and imaging tools are in development, which may provide more precise information on functional changes following treatment and/or the therapeutic action of experimental agents. When compared to appropriate controls, an improved functional outcome, in response to an experimental treatment, is the necessary goal of a clinical trial program. Several new functional outcome tools are being developed for measuring an individual's ability to engage in activities of daily living. Such clinical end points will need to be incorporated into Phase 2 and Phase 3 trials. QoL measures often do not correlate tightly with the above outcome tools, but may need to form part of Phase 3 trial measures.

Activities of Daily Living↗
PubMed2002

Neurocognitive assessment before and after cranioplasty.

OBJECTIVE: This paper addresses the possible value of neurocognitive tests on the evaluation of patients before and after cranioplasty for large cranial defects. METHODS: In a single patient with a large corrected cranial defect a detailed neurocognitive analysis was performed utilizing the EXIT interview and Cognistat before and after surgery. Planning and development of the surgical prosthesis were based on the pre-operative reconstruction of the head CT and on pre-operative pictures of the patient. Xenon-CT anatomical and quantitative cerebral blood flow (CBF) analysis was performed before and periodically after cranioplasty. FINDINGS: A significant improvement in major cognitive functions was observed after surgery. INTERPRETATION: Cognistat is a detailed neuropsychological battery that permits a better assessment of patients in diverse neurological conditions. The EXIT interview gives a better rapid assessment of cognition not provided by other methods, such as the mini-mental status examination (MMSE). The utilization of these techniques permits a better understanding of long-term outcomes for patients with diverse neurological conditions, including post-cranioplasty patients.

Adult↗
PubMed2001

Gacyclidine: a new neuroprotective agent acting at the N-methyl-D-aspartate receptor.

Gacyclidine is a new phencyclidine derivative with neuroprotective properties. Tritiated gacyclidine and its enantiomers bind to NMDA receptors with binding parameters similar to those of other non-competitive NMDA receptor antagonists. The (-)enantiomer, (-)GK11, exhibits an affinity (2.5 nM) similar to that of dizocilpine (MK-801), while the (+)enantiomer, (+)GK11, has a 10 times lower affinity. When its interaction with NMDA receptors is prevented, gacyclidine binds also to "non-NMDA" binding sites which are mainly located in the molecular layer of the cerebellum on the dendritic tree of Purkinje cells. These binding sites do not appear to be related to any known neurotransmitters. In primary cortical cultures, gacyclidine and its enantiomers, at 0.1 to 5.0 microM, prevent glutamate-induced neuronal death. In rats, in vivo neurotoxicity of gacyclidine is far low than that of MK-801. No necrotic neurons were detected in animals sacrificed at 18 or 96 h after treatment with gacyclidine (1, 5, 10 or 20 mg/kg i.v.). At the highest (20 mg/kg) but not the lower doses (1-100 mg/kg) electron microscopy revealed the presence of few cytoplasmic or intramitochondrial vacuoles. In soman-treated monkeys gacyclidine enhanced neuroprotective activity of "three drugs cocktail" (atropine + diazepam + pralidoxime). Moreover, in rats, gacyclidine exerts a dose- and time-dependent neuroprotection in three models of spinal cord lesion. Beneficial effects of gacyclidine include reduction of lesion size and improvement of functional parameters after injury. In traumatic brain injury models gacyclidine improves also behavioral parameters and neuronal survival. Optimal protection is obtained when gacyclidine is administered at 0 to 30 min after injury. It is, therefore, concluded that gacyclidine exhibits neuroprotective effects similar to those of other NMDA receptor antagonists, with the advantage of being substantially less neurotoxic maybe due to its interaction with "non-NMDA" binding sites.

Animals↗
PubMed2000

Neuroprotective effects of a novel NMDA antagonist, Gacyclidine, after experimental contusive spinal cord injury in adult rats.

The aim of this study was to analyze the optimal time-window for neuroprotection by a novel NMDA antagonist, Gacyclidine, after experimental spinal cord injury, in terms of its functional, histopathological and electrophysiological effects. This molecule has already demonstrated its capacity for reducing the extent of an ischemic lesion and is currently experimented in a clinical trial of spinal cord injury. In this study, the spinal cord of rats was damaged by a contusive method and the animals were treated by saline or 1 mg/kg of Gacyclidine i.v., 10, 30, 60 and 120 min after injury. The time-course of the motor score was evaluated on days 1, 7 and 18 after injury, and somatosensory evoked potentials were determined on day 20. The animals were then killed and the cross-sectional area of the spinal cord (at the epicenter of the injury, above and below the injury), was measured. Walking recovery was better (P<0.0125) in the group treated 10 min after injury than in the untreated injured animals after 18 days of injury. Motor performances were related to the preservation of a larger undamaged area of spinal cord at the level of the injury (P<0.0125). Somatosensory evoked potential amplitudes were also higher in this group. These results confirm that Gacyclidine attenuates spinal cord damage after an experimental spinal cord lesion. Recovery was better within the group treated 10 min after injury compared with the other groups, which certainly confirms that the acute time-course of glutamate release requires rapid pharmacological intervention to achieve good results.

Animals↗
PubMed2000

Neuroprotective effects of gacyclidine after experimental photochemical spinal cord lesion in adult rats: dose-window and time-window effects.

The aim of this study was to evaluate the efficacy, optimal dose, and optimal time-window of gacyclidine, a novel N-methyl-D-aspartate (NMDA) receptor antagonist, in terms of its functional, histopathological, and electrophysiological effects after experimental spinal cord injury. The spinal cord of rats was damaged by a photochemical method and the animals were treated by saline or gacyclidine at doses of 1, 2.5, or 5 mg/kg 10 min after injury or gacyclidine 1 mg/kg 10, 30, 60, and 120 min after injury. The time-course of the motor score (walking and inclined-plane stability) was evaluated until day 18, and somatosensory evoked potentials were determined on day 18. The animals were then sacrificed, and the cross-sectional area of the spinal cord (at the epicenter of the injury, above and below the injury) was measured. Walking recovery was better in most of the groups treated after injury than in the untreated injured animals. Motor performances were related to preservation of a larger undamaged area of spinal cord at the level of the injury and, interestingly, with prevention of extension of the anatomical lesion above the level of the injury. Somatosensory evoked potential amplitudes were often higher in treated groups. These results confirm that gacyclidine induces dose-dependent and time-dependent attenuation of spinal cord damage after an experimental vascular lesion. Although all three doses induced neuroprotective effects, recovery was greater and very homogeneous in the group treated with 1 mg/kg. Moreover, recovery was slightly better and more homogeneous within the groups treated 10 and 30 min after injury compared to the other groups. It appears that, according to the existing evidence, NMDA antagonists are an essential component in the elaboration of a neuroprotective strategy after spinal cord trauma.

Animals↗
PubMed2000

[Fronto-temporal dementia].

Defined barely one decade ago, Frontotemporal Dementia emerges as a new clinical entity that reestablishes the classical Pick's disease as part of a extensive syndrome with important and unsuspected prevalence. Frontotemporal Dementia includes all primary degenerative processes starting in the anterior portions of the brain. This type of dementia is clinically characterized by behavior and personality disorders, more than cognitive alterations. In the present research we performed a bibliographic review of the subject including clinical characteristics, laboratory tests, and neuropathology. Furthermore we assessed areas that require further development.

Dementia↗
PubMed1999

Variability of the fatigue response of paralyzed skeletal muscle in relation to the time after spinal cord injury: mechanical and electrophysiological characteristics.

The aim of this study was to determine the effect of the time after spinal cord injury (less than and greater than 10 months) on the mechanical and electrophysiological characteristics of muscle fatigue of the paralyzed electrically stimulated quadriceps muscle. Morphologically and histochemically, a relationship was observed between muscle fatigue and the delay from injury, revealing a critical period of enzymatic turning and a maximum peak of atrophy around the 10th month after the injury, followed by a long-term stabilization. Knee-torque output and M-wave variables (amplitude, latency, duration, and root mean square, RMS) of two muscular heads of the quadriceps were recorded in 19 paraplegic patients during a 120-s isometric contraction. The fatiguing muscle contraction was elicited by supramaximal continuous 20-Hz electrical stimulation. Compared to the chronic group, the acutely paralyzed group showed a greater resistance to fatigue (amount and rate of force decline, P < or = 0.01), smaller alterations of the M-wave amplitude and RMS, and a limited decrease of the muscle fiber conduction velocity (P < 0.05). Mechanical and electrophysiological changes during fatigue provided a clear functional support of the transformation of skeletal muscle under the lesion and of the existence of a critical period of muscular turn. In conclusion, when considering the artificial restoration of motor function, the evolution of the endurance and force-generating capabilities of the muscle actuator must be taken into account, particularly when tasks require important safety conditions (e.g., standing and walking).

Adult↗
PubMed1997

Psychosis in medical conditions: response to risperidone.

We report the response to risperidone in seven hospitalized, adult patients who presented psychotic symptoms etiologically related to a general medical condition. The conditions included brain surgery in two, and anticardiolipin syndrome, renal failure, epilepsy, lupus, and metastatic carcinoma in one each. Four patients had failed previous treatment with at least one typical antipsychotic agent. Response to risperidone was assessed by the Brief Psychiatric Rating Scale (BPRS). Serum was collected for measurement of steady-state trough risperidone and 9-hydroxyrisperidone concentrations at effective doses in three patients. Amelioration of psychotic symptoms was noted in all seven patients. Mean (+/- SD) BPRS scores were reduced significantly from baseline (63.0 +/- 15.1) to endpoint (27.0 +/- 3.5; p < 0.01). The mean effective daily dose of risperidone was 3.1 +/- .7 mg and time to response was 4.7 +/- 2.4 days. Risperidone was not present at detectable concentrations in the three patients studied. The mean steady-state trough serum concentration of 9-hydroxyrisperidone in the three patients assessed was 20.3 +/- 9.8 ng/ml. These preliminary findings, which suggest that risperidone is a safe and effective agent in patients with psychotic symptoms due to various medical conditions, need to be confirmed by randomized, antipsychotic comparison trials involving a larger number of patients.

Adult↗
PubMed1997

Vascular dementia, hypertension, and the brain.

Ischemic vascular dementia is a clinical syndrome of acquired intellectual impairment with ischemic cerebral injury resulting from occlusion of cerebral blood vessels and loss of cerebral tissue caused by cerebrovascular disease. With increasing life expectancy, the developed countries have experienced a shift towards a progressively older population. As the average age of the population increases, the prevalence of cerebrovascular disease and vascular dementia is likely to increase. The risk of vascular dementia seems to be correlated with the epidemiologic risk factors of stroke, namely hypertension. Hypertension is thought to be directly associated with vascular dementia and preliminary evidence suggests an association between elevated blood pressure and impairments in cognitive functioning. Recent investigations have found significant associations between hypertension and cerebral dilation and left hemisphere atrophy, and an increased incidence of white matter hyperintensities among hypertensives. Treatment and prevention of vascular dementia and cognitive dysfunction in the elderly require attention to cerebrovascular risk factors, particularly hypertension. Vascular dementias are potentially preventable and cases of Alzheimer's disease with vascular components are becoming increasingly recognized.

Brain↗
PubMed1997

Cerebral perfusion SPECT imaging in epileptic and nonepileptic seizures.

Patients with epileptic and nonepileptic seizures are commonly encountered in clinical practice, and they can pose a difficult diagnostic problem. We present two cases that show the difficult task of differentiating between true epileptic and nonepileptic or psychogenic seizures in some patients. The clinical presentations were complex and the use of video-monitored EEG alone was insufficient to make definitive diagnoses. Ictal and interictal Tc-99m HMPAO brain perfusion SPECT imaging examinations were used to help establish the correct diagnoses. This report describes the advantage of using the brain perfusion SPECT imaging examination. The injection of stabilized Tc-99m HMPAO during an ictal event followed by appropriate medical therapy provides a method of obtaining a reasonable image of relative perfusion (activity) during the seizure. These images can then be compared with interictal examinations and an epileptic or nonepileptic focus may be localized. The Tc-99m HMPAO brain perfusion SPECT imaging study was helpful in establishing the correct diagnosis in both cases.

Adult↗
PubMed1997

Application of ictal brain SPECT for differentiating epileptic from nonepileptic seizures.

The authors report 2 clinical cases that illustrate the difficulties with video-monitored EEG and the advantages of brain SPECT in differential diagnosis of true epileptic seizures and nonepileptic seizures. Injection of [99mTc]HMPAO at the time of the ictal event provides a means to obtain a SPECT image postictally for comparison with interictal examinations so that an epileptic or nonepileptic focus may be localized.

Adult↗
PubMed1996

Functional and histologic effects of a free nonvascularised muscle graft implanted into a reinnervated muscle after prolonged denervation.

Striated muscle atrophy and degeneration, which increase with the delay of denervation, represent two of the main causes for poor recovery following delayed nerve repair. The present study, using a rat model, tests the hypothesis that an adjunction of small, free, nonvascularised muscle grafts of contralateral healthy triceps into a chronically denervated triceps improves muscle regeneration and recovery following sciatic nerve repair delayed for 3 months. Our experiments seem to show a relative increase in mechanical properties in animals in which free muscle graft into the triceps was performed 3 weeks following nerve repair. The improvement of the regenerative process of muscles which have suffered a long period of denervation should be considered as an additional therapeutic procedure in the case of late nerve repair.

Animals↗
PubMed1996

Evaluation of outcome after intracranial aneurysm surgery: the neuropsychiatric approach.

BACKGROUND: With the reduction of mortality and gross neurologic morbidity of patients undergoing intracranial aneurysm surgery, the interest in outcome is shifting towards more subtle aspects such as cognitive deficits and psychosocial adjustment. METHODS: We discuss two different ways of measuring outcome in a sample of 20 patients who had intracranial aneurysm surgery. Patients were evaluated at discharge using the Karnofsky Scale and the Glasgow Outcome Scale. Six months after discharge we conducted a neuropsychiatric evaluation including cognitive, behavioral, and mood status assessment. RESULTS: Although 13 of out patients had a "good recovery, " 18 had some neuropsychiatric impairment. Comparing patients with "good recovery" with the remainder, patients with poorer outcomes tended to have a left pterional approach, a poorer "drive", and language disorders (p < 0.05). There was no correlation between out cognitive, mood, and behavioral assessment and the results of the Karnofsky and Glasgow Outcome Scales ( p > 0.05). CONCLUSIONS: we conclude that neuropsychiatric deficits are common after intracranial aneurysm surgery and that for our study the Karnofsky Scale and Glasgow Outcome Scale were not sensitive enough to detect residual impairment. therefore, it is important to develop brief tests and scales able to identify these problems and to complement the standard clinical neurological examination.

Adult↗
PubMed1996

Hantavirus pulmonary syndrome in Florida: association with the newly identified Black Creek Canal virus.

Hantavirus pulmonary syndrome (HPS) is a recently recognized viral zoonosis. The first recognized cases were caused by a newly described hantavirus. Sin Nombre virus (previously known as Muerto Canyon virus), isolated from Peromyscus maniculatus (deer mouse). We describe a 33-year-old Floridian man who resided outside the ecologic range of P maniculatus but was found to have serologic evidence of a hantavirus infection during evaluation of azotemia associated with adult respiratory distress syndrome. Small mammal trapping conducted around this patient's residence demonstrated the presence of antihantaviral antibodies in 13% of Sigmodon hispidus [cotton rat). Serologic testing using antigen derived from the Black Creek Canal hantavirus subsequently isolated from this rodent established that this patient was acutely infected with this new pathogenic American hantavirus. HPS is not confined to the geographical distribution of P maniculatus and should be suspected in individuals with febrile respiratory syndromes, perhaps associated with azotemia, throughout the continental United States.

Acute Kidney Injury↗