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[Neurophysiological evaluation using multimodal sensory evoked potentials in patients in coma: general aspects].

Noninvasive sensory evoked potentials (SEP) performed at bedside in the Intensive Care Unit for patients in coma can be helpful in establishing both a diagnosis and a prognosis. Based on a more than 6-year experience on this subject, the authors discuss general aspects concerning these EP, their probable known generators, and propose a classification depicting different aspects observed for flash visual EP (F-VEP), brainstem auditory EP (BAEP), and median nerve somato-sensory EP (SSEP). Isolated, SSEP shows the best diagnostic and prognostic performance. Nevertheless, the authors consider that multimodality SEP are even better than any isolated EP study; cross-correlating information generated through a horizontal (F-VEP), a vertical (SSEP), and a pathway focusing brainstem in greater detail (BAEP) allows the neurophysiological establishment of the level of lesion in the CNS from a better perspective; besides, SEP can help setting the diagnosis of brain (encephalic) death, and the diagnosis of particular problems concerning each pathway. Notwithstanding, most important is prognosis definition, and the findings are summarized. Abnormal BAEP implies bad prognosis, as would be expected considering the severity of a brainstem lesion; on the other hand, a normal BAEP per se does not allow a precise definition, resting on other EP the role prognosis characterization. SSEP if bilaterally normal or only mildly abnormal imply good prognosis; bilateral absence of SSEP thalamo-cortical components has always carried a bad prognosis, since younger patients may at best evolve into a persistent vegetative state; SSEP intermediary results are more often accompanied by variable evolution. FVEP results parallel those of SSEP.

Coma↗

[Multimodal iatrogenic apathy].

The present paper reports on five patients who developed apathy as a peculiar side effect of antidepressants. Their behavioral and psychopathological changes were primarily due to the near-absence of emotional experience, a key characteristic that distinguishes apathy from avolition and abulia. The emergence of apathy in the course of an antidepressant treatment should raise the suspicion of an adverse effect of the drug and lead to its prompt withdrawal. A sample of the relevant clinical evidence favoring the distinction of apathy confined to a single sensory domain ("unimodal apathy") from apathy confined to more than one sensory realm ("multimodal apathy") is reviewed. From a pathophysiological standpoint, it would appear that neural nets centered in the amygdala-temporo polar cortex are critical for the integration of sensory perceptions and mental imagery with appropriate emotional tone and quality as well as with their accompanying somatic markers, as they receive afferents from the major projection systems of the prosencephalon and lie in nodes strategic to modify the ongoing activity of multiple parallel brain systems. The fact that one common symptom can be produced by such a heterogeneous family of substances points to a shared neurochemical mechanism of action. At present, discrete cerebral serotoninergic circuits would appear to be suitable candidates for such a role. Cases as these may be critical for the understanding of the cerebral organization of emotions in man, lending support to the notion that distinct neurochemical systems mediate discrete psychopathological symptoms.

Activities of Daily Living↗

Timing multimodal events in pigeons.

The peak procedure was used in two experiments to study pigeons' ability to time multimodal events. In the first experiment, birds were trained to time a single event consisting of a 9-s tone or light followed by a 21-s fixed interval associated with a signal of light or tone (signal of the other modality). On occasional empty trials, different lengths of the first signal were followed by a long period of the second signal. Peak response times as a function of the duration of the first signal were linear and had a slope of close to one in all birds. This indicates that the birds were timing only the second signal. In a second experiment, two complex events were used in training. One consisted of a 9-s tone or light followed by a 21-s fixed interval associated with a light or tone. The other consisted of a 21-s tone or light followed by a 9-s fixed interval associated with a light or tone. Different durations of the first signal were again used on empty trials. Peak response times as a function of the duration of the first signal were again linear in all birds. The slope of the function was less than one but greater than zero for 3 birds. This indicates that these birds were partly timing the entire complex event of 30-s duration and partly timing only the second signal of the event. A model is proposed in which the bird takes as a criterion for timing a weighted average of different target criteria. Comparisons with the performance of rats are made.

Journal Article↗

Efficacy of periarticular multimodal drug injection in total knee arthroplasty. A randomized trial.

BACKGROUND: Postoperative analgesia with the use of parenteral opioids or epidural analgesia can be associated with troublesome side effects. Good perioperative analgesia facilitates rehabilitation, improves patient satisfaction, and may reduce the hospital stay. We investigated the analgesic effect of locally injected drugs around a total knee prosthesis. METHODS: Sixty-four patients undergoing total knee arthroplasty were randomized either to receive a periarticular intraoperative injection containing ropivacaine, ketorolac, epimorphine, and epinephrine or to receive no injection. The perioperative analgesic regimen was standardized. All patients in both groups received patient-controlled analgesia for twenty-four hours after the surgery, and this was followed by standard analgesia. Visual analog scores for pain, during activity and at rest, and for patient satisfaction were recorded preoperatively and postoperatively and at the six-week follow-up examination. The consumption of patient-controlled analgesia at specific postoperative time-points and the overall analgesic requirement were measured. RESULTS: The patients who had received the injection used significantly less patient-controlled analgesia at six hours, at twelve hours, and over the first twenty-four hours after the surgery. In addition, they had higher visual analog scores for patient satisfaction and lower visual analog scores for pain during activity in the post-anesthetic-care unit and four hours after the operation. No cardiac or central nervous system toxicity was observed. CONCLUSIONS: Intraoperative periarticular injection with multimodal drugs can significantly reduce the requirements for patient-controlled analgesia and improve patient satisfaction, with no apparent risks, following total knee arthroplasty.

Aged↗

Multimodality imaging of tumor integrin alphavbeta3 expression.

Most solid tumors are angiogenesis dependent. Anti-angiogenic pharmaceuticals that inhibit the growth of new blood vessels offer considerable promise as anti-cancer agents. With increasing numbers of anti-angiogenic drugs in clinical trials, there is an urgent need for detailed characterization of the heterogeneity of tumor vasculature and dissection of the complex network of mechanisms that control tumor angiogenesis. Non-invasive molecular imaging will play a key role in individualized anti-angiogenic therapy based upon molecular features of the new blood vessel growth. Integrin alpha(v)beta(3), which binds several ligands via an RGD tripeptide sequence, is uniquely expressed in tumor vasculature and aggressive tumor cells, making it a potential target for anti-angiogenic interventions. This review highlights some recent advances in multimodality imaging of tumor integrin expression with emphasis on positron emission tomography (PET).

Drug Design↗

[A comparative study of multimodality evoked potentials and computed tomography in head injuries].

Multimodality evoked potentials (EPs) or three types of EPs--auditory brainstem response (ABR), somatosensory evoked potential (SEP), and visual evoked potential (VEP)--were recorded in 51 cases of traumatic intracranial hemorrhage within 3 days after injury. In order to assess these EPs, five EP grades were constructed, from normal, Grade I, to highly abnormal, Grade V. Furthermore, an EP pattern classification was devised to integrate the respective EP grades. Namely, PA, consisting of all three EPs within Grades I-III; PB, composed of one type of EP or both ABR and VEP at Grades IV and V; PC, consisting of both SEP and VEP at Grades IV and V; PD, comprising both ABR and SEP at Grades IV and V; and PE, covering all three EPs at Grades IV and V. PA signifies "no severe damage," PB, "localized damage," PC, "severe cerebral damage," PD, "severe brainstem damage," and PE, "severe diffuse damage." The results when compared with computed tomography (CT) findings were as follows: 1) The size of hematoma correlated with the SEP grade in 16 cases of acute epidural hematoma; a hematoma diameter of 17.5 mm was the threshold value at which SEP abnormalities developed. Eleven patients who underwent surgical removal of the hematoma showed "no severe damage," and the outcome was good. 2) In 13 cases of acute subdural hematoma, six cases revealed "severe cerebral damage" or "severe diffuse damage." In such cases, the degree of damage was not related to the hematoma size, and the outcome was very poor. 3) In 13 cases of a solitary contusional hemorrhage, only one case revealed "severe diffuse damage" and subsequently died.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Multimodality treatment for large and critically located arteriovenous malformations.

To define the current status of the multimodality treatment for large and critically located arteriovenous malformations (AVMs), we have made a retrospective review of 54 consecutive patients with Spetzler-Martin grade IV and V AVMs. The size of nidus is larger than 3 cm in diameter in all cases. Initially, all but one were treated by nidus embolization with the aim of size reduction. Only one patient had complete nidus occlusion by embolization alone. In 52 patients, the obliteration rate of nidus volume averaged 60% after embolization. Ten patients underwent complete surgical resection of AVMs following embolization with no postoperative neurological deterioration. Thirty-one patients underwent stereotactic radiosurgery following embolization. At the time of this analysis, 30 patients underwent follow-up angiography 2-3 years after radiosurgery. The results of radiosurgery correlated well with the preradiosurgical AVM volume. Of 16 patients with small residual AVMs (< 10 cm3, a mean volume of 4.7 cm3), nine (56%) had complete obliteration, and six (38%) had near-total or subtotal obliteration by 3 years after radiosurgery. In contrast, of 14 patients with large residual AVMs (> or = 10 cm3, a mean volume of 17.9 cm3), only two (14%) had complete obliteration, and eight (57%) had near-total or subtotal obliteration. Repeat radiosurgery was performed for the patients with remaining AVMs at 3-year follow-up review. This study indicates that a certain number of large and critically located AVMs can be safely treated by either microsurgery or radiosurgery following a significant volume reduction by nidus embolization. The present data also suggest the need and possible role of repeat radiosurgery in improving complete obliteration rate of large difficult AVMs, since many of those AVMs have significantly responded to initial radiosurgery.

Adolescent↗

Complete recovery of visual functions after multimodality treatment for intrinsic chiasmatic-hypothalamic astrocytoma--case report.

A 21-year-old female was admitted with complaints of severe impairment of vision. The visual acuity was 0.02 in both eyes along with residual visual fields and central scotomas. Neuroimaging disclosed a chiasmatic-hypothalamic glioma. Surgery was performed with partial removal of the intrachiasmatic part of the intrinsic tumor. The histological diagnosis was fibrillary astrocytoma. Progressive recovery of vision began in the first week after surgery. Adjuvant treatment included one course of fractionated radiation therapy and six courses of chemotherapy. Complete recovery of visual acuity occurred after 10 months, and the visual fields were restored after an additional 6 months. Her vision has been stable during 2 years of follow up. The prognosis for recovery of vision after treatment of optic pathway gliomas mainly depends on the severity of visual loss at admission and is negatively influenced by intrinsic tumor growth, symmetrical extension, and involvement of the chiasm. Despite the presence of all these factors in the present case, multimodality management resulted in the complete recovery of visual functions. Surgery may be indicated in cases of intrinsic chiasmatic gliomas complicated by severe visual loss.

Adult↗

Large paraclinoid aneurysm with a calcified neck treated by tailored multimodality procedures.

A 68-year-old woman presented with a large paraclinoid aneurysm with a calcified neck causing visual symptoms. Direct clipping was hazardous because of severe calcification of the neck. Endovascular internal trapping was difficult because of the short distance between the neck and the origin of the posterior communicating artery. Proximal occlusion was likely to be less effective because of large collateral back flow to the aneurysm via the ophthalmic artery (OphA). The aneurysm was successfully treated by a combination of a high-flow bypass, intraoperative coil embolization of the parent artery including the origin of the OphA, and clipping of the internal carotid artery distal to the aneurysm. Paraclinoid aneurysms may be difficult to treat by the simple application of direct clipping, endovascular coiling, or trapping. Multimodality procedures can be tailored to treat such aneurysms.

Aged↗

[Multimodal evoked potential abnormalities in patients with Wilson's disease].

The aim of this study was to investigate the involvement of the following functional systems: somatosensory evoked potentials (SSEP), visual evoked potentials (VEP), and event related potentials (ERP), in twenty patients with Wilson's disease (WD). VEP and SSEP abnormalities were discovered in 8 patients respectively (40%), whereas ERP were either absent or, in the case of 10 patients (50%), had significantly prolonged P-300 latencies. Taken together, at least one evoked potential abnormality was discovered in 17 patients (85%). Only in 3 patients (15%), involving either the isolated hepatic type of disease or short illness duration of the neurological type, were normal evoked potential findings observed. Our findings suggest the usefulness of multimodal evoked potential abnormalities in the evaluation of subclinical manifestations in patients with WD.

Adolescent↗

A multimodal approach to elimination of stuttering.

Various approaches have been used in the treatment of stuttering. However, none of these approaches have been systematically incorporated via a multifaceted treatment program for the elimination of this disorder. The following case of a 15-yr.-old stutterer is presented to illustrate Lazarus' Multimodal Behavior Therapy Model, which is proposed to integrate various procedures whose singular effectiveness has been demonstrated.

Adolescent↗

A follow-up of alcoholics treated by multimodal therapy.

A general hospital sponsored for the psychotherapeutic treatment of alcoholism is described. In this context a multimodal approach, emphasizing methods derived from principles of learning, is applied to training the individual in new life-style skills for the management of alcoholism. Demographic characteristics of the population served by the program are of a predominantly blue collar clientele, mostly employed (72%), married (61%), and from urban centers (95%). Attrition as a major problem in evaluating results at the follow-up stage is identified and a method of reporting follow-up results taking this factor into account is presented. This method showed that under the most stringent conditions for reporting results, 36.64% of a sample of 131 alcoholics were showing improvement at 12 months, while under the least stringent condition 84% were showing some improvement over the same period.

Adult↗

Designing of thermosensitive liposomes from natural lipids for multimodality cancer therapy.

Thermosensitive liposomes prepared from synthetic lipids such as dipalmitoyl phosphatidylcholine, distearoyl phosphatidyl choline and cholesterol (Ch) have been tried for local drug release in response to hyperthermia for achieving tumour drug targeting. Herein we report a novel method of preparation of temperature-sensitive liposomes using natural lipids egg phosphatidylcholine (PC):Ch (7:1 molar ratio) and ethanol 6% (v/v) having a transition temperature of 43 degrees C, temperature attainable by local hyperthermic treatment of tumours. The anticancer drug decarbazine [5-(3,3'-dimethyl-1-triazino) imidazole-4-carboxamide] was entrapped in these liposomes. The in vivo efficacy of temperature-sensitive unilamellar vesicles encapsulated decarbazine in combination with hyperthermia was determined in murine fibrosarcomas. These PC:Ch liposomes are biodegradable, non-toxic and more cost effective in comparison with liposomes prepared from synthetic lipids for use in multimodality cancer therapy.

Animals↗

Locally advanced adenocarcinoma of the breast without distant metastasis treated with multimodal therapies.

Locally advanced breast cancer has been treated with a variety of primary treatments with or without adjuvant therapies. This study combines radiation, chemotherapy, and surgery as a multimodal program for Stage III breast cancer. Radiation was started on day 1: 4600 rad were administered to the breast and 4500 rad were administered to the axilla and supraclavicular areas. Chemotherapy was started on day 1 with weekly intravenous injections of 5-fluorouracil (5FU) (300 mg/m2), methotrexate (15 mg/m2), vincristine (0.625 mg/m2), oral cytoxan (60 mg/m2), and prednisone (30 mg/m2 for two weeks, then 20 mg/m2 for two weeks, then 10 mg/m2 for two weeks). The 5FU, methotrexate, and cytoxan were given for 10 months postsurgery. This combination of modalities produced a complete remission in all 13 patients with Stage III breast cancer after two months of therapy. The median disease-free period was two years. The median survival was 44 months. This approach to the management of Stage III breast cancer is worthy of further investigation.

Adenocarcinoma↗

Multimodality therapy: radiation and continuous concomitant cis-platinum and PKC inhibition in a cervical carcinoma model.

The addition of chemotherapy to radiation therapy has the potential to sterilize micrometastases and tumor foci adjacent and peripheral to the treatment field, so as to enhance local control of malignancy and improve primary and salvage therapy. Studies were done to investigate the effects of combining cisplatin (CP), the most active single agent in squamous-cell cancer of the cervix, with irradiation and the addition of a protein kinase C (PKC) inhibitor. This initial report of these studies describes our experience in exposing human cervical carcinoma (HeLa-S3) cells grown in culture as multicellular tumor spheroids to continuous CP combined with radiation in an attempt to mimic both clinically achievable serum concentrations of CP and a weekly fractionated-dose environment. Radiation-dose-dependent delays of spheroid growth were not significantly increased in the presence of the PKC inhibitor 7-OH-staurosporine (UCN-01) at 1.0 nM and 10.0 nM concentrations. When dose comparisons at 8 Gy alone (2 Gy x 4 fractions) were made for combined therapy with either CP alone (1.0 microgram/ml) or UCN-01 alone, absolute delays in spheroid growth at the highest concentrations used were comparable (range: 37-41 days). Although these data alone would not support minimal chemotherapeutic interaction, it appears that the overall effects observed for combination therapy were predominately radiation-dose dependent. The combination of UCN-01 plus CP (0.5 and 1.0 mu/ml, respectively) was effective in increasing the cytostatic and cytotoxic effects of irradiation at 4 Gy (2 Gy x 2 fractions). Observations made as early as day 4 and day 7 posttreatment were indicative of > or = 40% and 60%, respectively, of morphological damage. Spheroid growth was essentially static at these doses over the evaluation time of 60 days. Intracellular junctions were disorganized, and spheroid swelling was evident and contributed to the modest dimensional changes observed after treatment. No surviving fractions could be generated from spheroids that were mechanically disrupted, trypsinized, and plated at day 7 after the initiation of treatment. At 2 months, 88% (14/16) and 94% (15/16) of the multimodality treatment groups (4 Gy + UCN-01 + CP [0.5 and 1.0 mu/ml], respectively) had sterilized spheroids, indicating that the CP concentration dependence may not be a sole determinant of efficacy. Our therapeutic strategy for combining irradiation with CP was based on the contemporary use of CP as the most successful agent in producing high survival rates in gynecological malignancy. The combination of UCN-01 with CP and irradiation may, however, represent a more effective strategy for enhancing future cisplatin-based chemotherapy regimens.

Alkaloids↗

Successful multimodal therapy for kaposiform hemangioendothelioma complicated by Kasabach-Merritt phenomenon: case report and review of the literature.

We present the management challenge provided by a patient with kaposiform hemangioendothelioma associated with Kasabach-Merritt phenomenon. A female child presented at 14 months of age with an ecchymotic swelling of her right upper arm and axilla. Subsequently, she developed profound thrombocytopenia and hypofibrinogenemia (Kasabach-Merritt phenomenon). Biopsy of the lesion revealed kaposiform hemangioendothelioma, which has been reported as the predominant pathologic diagnosis associated with Kasabach-Merritt phenomenon. To achieve involution of the lesion and preserve function of the arm, the following interventions were involved: embolization, systemic interferon, cyclophosphamide, epsilon aminocaproic acid, and compression therapy. The clinical management of this patient was formidable until we arrived at the proper combination of therapies. Multimodal intervention may be required to manage fastidious hemangioendotheliomas of childhood, achieve clinical improvement, and prevent further morbidity.

Female↗

Prediction of successful response to multimodality treatment among heroin addicts.

In an effort to identify predictor variables associated with successful response to multimodality treatment among heroin addicts, this investigation compared addict-clients classified by means of behavioral ratings into success and failure groups on 16 social history and 18 psychological variables using stepwise discrimination techniques. Statistical analyses correctly classified 100% of the treatment failure group and 92% of treatment successes. Successful clients were characterized by more advanced educational achievement at intake, later onset of opiate use, higher scores on MMPI Scales Es and L, and lower scores on MMPI Scale 7. Results suggest that collection and nanlyses of such data at intake may provide a reliable basis for prediction of treatment outcome as well as an objective means for early identification of "high risk" individuals who may require a more concentrated and individualized therapeutic effort.

Adult↗

Management of malignant glioma: role of surgery in relation to multimodality therapy.

The goals of surgery for malignant glioma are to establish a histological diagnosis and to achieve mechanical cytoreduction to reduce intracranial pressure (ICP) and possibly alter tumor kinetics. There is controversy concerning the question whether the glioma is a focal or diffuse process; it appears that there may be variability between the two extremes in individual cases. The question of the value of surgery has also been controversial. Review of the literature suggests that both early and long-term postoperative outcome after radical surgical resection are better than the results of either partial resection or simple biopsy, in terms of neurological status and duration of survival. Similarly, reoperation for recurrence of glioma offers reasonable extension of quality survival. Despite the desirability of extensive cytoreductive surgery for malignant gliomas, the presence of viable infiltrative cells beyond the margins of the resection necessitate that surgery be a part of an aggressive multimodality therapeutic approach. Adjunctive measures to control the infiltrative component include newer forms of radiotherapy (such as stereotaxic radiosurgery) and newer delivery techniques for chemotherapy (agents impregnated in biodegradable polymers implanted in the tumor bed after surgical resection), and possibly immunotherapy and gene therapy as they may become feasible in the future. The strategy for management of malignant glioma thus consists of a combination of extensive surgical resection to reduce the accessible tumor burden, followed in rapid sequence by measures to control the infiltrative portion of the tumor. It is recommended that these measures be offered 'up front' rather than delaying treatment until there is clinical or radiographic evidence of tumor recurrence.

Adult↗