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Psychophysical isolation of the modality responsible for detecting multimodal stimuli: a chemosensory example.

Multiple sense modalities can be stimulated conjointly by a physically complex item, such as a predator, and also by a physically solitary stimulus that acts on multiple receptor classes. As a prime example of this latter group, l-menthol from mint stimulates taste, smell, and several somatosensory submodalities. In 6 experiments that used a variety of psychometric techniques, the authors experimentally isolated the modality by which l-menthol is detected in the upper airways (the nose and mouth). Interestingly, absolute detection in both the nasal and oral cavities was based on olfaction and not stinging, cooling, or taste. These experiments illustrate how the sensory modality responsible for detecting a multimodal or multisensory stimulus can be psychophysically isolated.

Adolescent↗

Emotion experience and expression across the adult life span: insights from a multimodal assessment study.

This investigation represents a multimodal study of age-related differences in experienced and expressed affect and in emotion regulatory skills in a sample of young, middle-aged, and older adults (N=96), testing formulations derived from differential emotions theory. The experimental session consisted of a 10-min anger induction and a 10-min sadness induction using a relived emotion task; participants were also randomly assigned to an inhibition or noninhibition condition. In addition to subjective ratings of emotional experience provided by participants, their facial behavior was coded using an objective facial affect coding system; a content analysis also was applied to the emotion narratives. Separate repeated measures analyses of variance applied to each emotion domain indicated age differences in the co-occurrence of negative emotions and co-occurrence of positive and negative emotions across domains, thus extending the finding of emotion heterogeneity or complexity in emotion experience to facial behavior and verbal narratives. The authors also found that the inhibition condition resulted in a different pattern of results in the older versus middle-aged and younger adults. The intensity and frequency of discrete emotions were similar across age groups, with a few exceptions. Overall, the findings were generally consistent with differential emotions theory.

Adult↗

Multimodal profiling reveals tissue-directed signatures of human immune cells altered with age.

The immune system comprises multiple cell lineages and subsets maintained in tissues throughout the lifespan, with unknown effects of tissue and age on immune cell function. Here we comprehensively profiled RNA and surface protein expression of over 1.25 million immune cells from blood and lymphoid and mucosal tissues from 24 organ donors aged 20-75 years. We annotated major lineages (T cells, B cells, innate lymphoid cells and myeloid cells) and corresponding subsets using a multimodal classifier and probabilistic modeling for comparison across tissue sites and age. We identified dominant site-specific effects on immune cell composition and function across lineages; age-associated effects were manifested by site and lineage for macrophages in mucosal sites, B cells in lymphoid organs, and circulating T cells and natural killer cells across blood and tissues. Our results reveal tissue-specific signatures of immune homeostasis throughout the body, from which to define immune pathologies across the human lifespan.

Humans↗

A multimodal treatment approach including high-dose chemotherapy in very advanced gastric cancer: evidence for control of metastatic disease.

The present multimodal treatment approach was designed to achieve prolonged tumor control in advanced gastric cancer. A total of 26 patients with stage IV gastric cancer (metastatic disease n=25), ECOG performance status 0-3 and laparoscopically evaluated peritoneal status received a modified EAP schedule to prove chemosensitivity and to mobilize autologous peripheral blood stem cells (aPBSC). Patients without progressive disease proceeded to tandem high-dose chemotherapy (HD-CT) and aPBSCT. Patients with >50% reduction of the target lesion received a second cycle of HD-CT. Responders were selected for local R0 resections (D2 resection) according clinical criteria. Of 26 patients, 20(77%) achieved partial remission after dose-intensive chemotherapy: local R0 resection was achieved in 12 out of 14 patients selected for surgery (46% of all patients). Eight of these R0-resected patients initially had peritoneal carcinomatosis. With a median follow-up of 3.2 years, four patients are still alive. The median overall survival was 8.4 months (CI 2.5-14.4 months), for histologic regression grade 3 (seven out of 25 patients, 28%) 29 months (CI 12-46 months). The combined treatment approach is tolerable and feasible in advanced disease and opens a therapeutic window for a significant proportion of patients, even in cases with histologically proven peritoneal carcinomatosis.

Adult↗

Multistep and multimode cortical anchoring of tea1p at cell tips in fission yeast.

The fission yeast cell-polarity regulator tea1p is targeted to cell tips by association with growing microtubule ends. Tea1p is subsequently anchored at the cell cortex at cell tips via an unknown mechanism that requires both the tea1p carboxy-terminus and the membrane protein mod5p. Here, we show that a tea1p-related protein, tea3p, binds independently to both mod5p and tea1p, and that tea1p and mod5p can also interact directly, independent of tea3p. Despite their related structures, different regions of tea1p and tea3p are required for their respective interactions with an essential central region of mod5p. We demonstrate that tea3p is required for proper cortical localization of tea1p, specifically at nongrowing cell tips, and that tea1p and mod5p are independently required for tea3p localization. Further, we find that tea3p fused to GFP or mCherry is cotransported with tea1p by microtubules to cell tips, but this occurs only in the absence of mod5p. These results suggest that independent protein-protein interactions among tea1p, tea3p and mod5p collectively contribute to tea1p anchoring at cell tips via a multistep and multimode mechanism.

Cell Polarity↗

Bump-hunting for the proficiency tester--searching for multimodality.

Kernel density estimation is a method for producing a smooth density approximation to a dataset and avoiding some of the problems associated with histograms. If it is used with a degree of smoothing determined by a fitness for purpose criterion, it can be applied to proficiency test data in order to test for multimodality in the z-scores. The bootstrap is an essential additional technique to determine how rugged the initially estimated kernel density is: the random resampling of the data in the bootstrap simulates a complete blind repeat of the proficiency test. In addition, useful estimates of the standard error of a mode can be thus obtained. It is suggested that a mode and its standard error can be used as an assigned value and its standard uncertainty.

Journal Article↗

Multimodality treatment in the control of deep musculoaponeurotic fibromatosis.

BACKGROUND: Deep musculoaponeurotic fibromatoses are rare soft tissue neoplasms with a propensity for local recurrence. METHODS: A retrospective analysis was carried out of the factors contributing to local disease control in 75 patients treated between 1963 and 1993. RESULTS: Multivariate analysis identified the type of surgical excision (P < 0.001) and involvement of pathological resection margins (P < 0.02) as significant factors contributing to local recurrence. After a median follow up of 47 months (range 24 months to 29 years) 31 (49 per cent) of the 63 patients who had an 'adequate' surgical resection developed local recurrence. The median time before development of local recurrence was 83.4 (range 8-129) months in patients with clear pathological resection margins. This was significantly shortened to 13.1 (range 2-35) months in those with positive margins (P < 0.001). CONCLUSION: Adequate surgical extirpation is the most important determinant in local disease control. Treatment of local recurrence ranged from observation during periods of disease stabilization to multimodality treatment for aggressive disease.

Adult↗

Hospital stay of 2 days after open sigmoidectomy with a multimodal rehabilitation programme.

BACKGROUND: Hospital stay after colonic surgery is usually between 5 and 10 days, limiting factors being pain, ileus, organ dysfunction and fatigue. Single-modality intervention to reduce these factors with laparoscopic surgery usually requires a hospital stay of 5 days. This paper reports the results of a multimodal rehabilitation regimen after open sigmoidectomy. METHODS: Sixteen unselected patients scheduled for elective sigmoid resection (median age 71 years) underwent operation under combined spinal-epidural anaesthesia. After operation, epidural analgesia was continued for 48 h, with immediate oral nutrition and mobilization, and with planned discharge 2 days after surgery. RESULTS: The median postoperative hospital stay was 2 (range 2-6) days (48 h), patients being mobilized for a median of 5 h on the second postoperative day (24-48 h) and for 10 h on the third day (48-72 h). Within 48 h of operation 14 patients had an oral intake of 2000 ml or more and 15 had resumed defaecation. Fatigue and pain scores were low during the first 8-9 days after operation, with a median of 13 h of mobilization per day after discharge. There were no medical or surgical complications during 30 days of follow-up, except for two patients who suffered postspinal headache. CONCLUSION: Postoperative recovery after open colonic surgery may be accelerated by effective pain relief integrated into an accelerated rehabilitation programme.

Adult↗

Nonlinear bio-photonic crystal effects revealed with multimodal nonlinear microscopy.

Highly optically active nonlinear bio-photonic crystalline and semicrystalline structures in living cells were studied by a novel multimodal nonlinear microscopy. Numerous biological structures, including stacked membranes and aligned protein structures are highly organized on a nanoscale and have been found to exhibit strong optical activities through second-harmonic generation (SHG) interactions, behaving similarly to man-made nonlinear photonic crystals. The microscopic technology used in this study is based on a combination of different imaging modes including SHG, third-harmonic generation, and multiphoton-induced fluorescence. With no energy release during harmonic generation processes, the nonlinear-photonic-crystal-like SHG activity is useful for investigating the dynamics of structure-function relationships at subcellular levels and is ideal for studying living cells, as minimal or no preparation is required.

Animals↗

Adenocarcinoma of the female urethral diverticulum treated by multimodality therapy.

A 75-year-old female presented with a 7-month history of intermittent macrohematuria and urinary retention. Physical examination revealed a firm, round mass on the anterior vaginal wall. The diagnosis by urethroscopy and radiological evaluation was localized urethral diverticular tumor. Pathological examination of the biopsy specimen revealed adenocarcinoma. The patient received two courses of intra-arterial and systemic chemotherapy using cisplatin, 5-fluorouracil and leucovorin, followed by radiation to the urethra. The tumor shrunk markedly after chemotherapy. The patient underwent total urethrectomy and vesicostomy. Two years after the operation, she had no evidence of recurrence. Adenocarcinoma of the female urethral diverticulum is rare and has been treated by surgery and/or radiation. The present case is the first case of it being treated by multimodality therapy including chemotherapy.

Adenocarcinoma↗

Successful long-term disease-free survival following multimodal treatments in a patient with a repeatedly recurrent refractory adrenal cortical carcinoma.

A 47-year-old male patient underwent surgery for a 10-cm adrenal cortical carcinoma. A large invasive adrenal mass was surgically removed en bloc with the right kidney and the lower lobe of the liver. Two months postoperatively, a 7-cm recurrent mass developed in the right psoas muscle. After a partial response was achieved by irradiation (40 Gy) and high-dose chemotherapy (carboplatin and etoposide) with peripheral blood stem cell transplantation, the patient underwent surgery with a wide excision of the psoas muscle. Twelve months after the initial surgery, an 8-cm rib metastasis developed and the patient again underwent surgery after a combination of irradiation (50 Gy) and chemotherapy (cisplatin and etoposide). The patient has been doing well without any evidence of recurrence for 5 years. Refractory or metastatic adrenal cortical carcinomas have been thought to be lethal, therefore, the present case provides support for multimodal treatments of refractory adrenocortical cancers.

Adrenocortical Carcinoma↗

Multimodal hyperspectral imaging for the noninvasive diagnosis of cervical neoplasia.

OBJECTIVE: To determine the ability of Multimodal Hyperspectral Imaging (MHI) to noninvasively detect, localize and diagnose cervical neoplasia. MATERIALS AND METHODS: The cervical epithelium was interrogated by MHI using tissue fluorescence and reflectance measurements after the probe was placed on the ectocervix. A Papanicolaou smear was taken, and a colposcopic examination was performed and cervical histologic specimens were collected, when indicated. MHI and Pap smear sensitivity and specificity data were compared with colposcopic and histologic results. RESULTS: Nineteen patients had CIN2 or higher, 30 had CIN1, 34 had benign cellular changes or metaplasia, and 28 were normal by both Pap smear and colposcopic examination. At equal specificity (70%) for both tests, the sensitivity of MHI was 97%, compared to 72% for the Pap smear. CONCLUSION: MHI detected cervical cancer precursors at a rate greater than that obtained by a simultaneously collected Pap smear.

Journal Article↗

Multimodal treatment of peritoneal carcinomatosis and sarcomatosis.

Peritoneal carcinomatosis and sarcomatosis (PCS) are short-term fatal conditions amenable only to palliative treatment. They are generally considered as a systemic disease at clinical presentation, and are resistant to standard treatments. However, there may be in the natural history a phase of loco-regional tumour spread during which the tumour may still be curable. Surgical treatment alone, or in combination with systemic chemotherapy, has yielded poor results in terms of survival and quality of life. One approach is cytoreductive surgery (CS) combined with the intraperitoneal administration of antiblastic agents. This may diminish any residual tumour following macroscopic excision and may overcome the pharmacokinetic limits of systemic chemotherapy. A further improvement in this multimodal approach may be achieved by the use of hyperthermic intraperitoneal intraoperative chemotherapy (HIIC). Results so far have been encouraging. However, series reported in the literature are relatively small and heterogeneous, and clinical and technical factors which include the selection of patients, optimal drugs dosage and temperature, evaluation of outcome and costs are still under discussion.

Antineoplastic Agents↗

Aggressive multimodality therapy for patients with locally advanced esophageal cancer: is there a role for amifostine?

Most patients with locally advanced esophageal cancer die from their disease, despite complete surgical extirpation of tumor or institution of aggressive, multimodality treatment. Nevertheless, a favorable trend emerging in the management of such patients is that "more therapy is better." This review describes several studies indicating that aggressive, combined-modality therapy provides a survival advantage for patients with locally advanced esophageal cancer. An ongoing North Central Cancer Treatment Group trial further capitalizes on the concept of "more is better," and tests subcutaneous amifostine (Ethyol, WR-2721; MedImmune, Inc, Gaithersburg, MD) to balance the need for aggressive therapy with the need to mitigate associated toxicity.

Amifostine↗

Opioid-free analgesia following total knee arthroplasty--a multimodal approach using continuous lumbar plexus (psoas compartment) block, acetaminophen, and ketorolac.

BACKGROUND AND OBJECTIVES: Traditionally, postoperative analgesia following total knee arthroplasty (TKA) has been provided by neuraxial or peripheral regional techniques with supplemental administration of opioids. We report an alternative method of postoperative pain management for patients undergoing TKA in whom the use of systemic or neuraxial opioids may result in significant side effects. CASE REPORT: A 74-year-old woman with a history of protracted nausea and vomiting after systemic and neuraxial opioid administration presented for left total knee arthroplasty. A spinal anesthetic with postoperative continuous lumbar plexus (psoas) analgesia was planned. A quadriceps motor response was elicited and a 20-gauge catheter was advanced through an 18-gauge insulated Tuohy needle into the psoas sheath. After 30 mL of bupivacaine 0.5% with 100 microg clonidine was administered through the psoas catheter, a spinal anesthetic (2 mL 0.5% bupivacaine at the L2-3 interspace) was performed. A continuous psoas infusion of 0.2% bupivacaine with 2 microg/mL clonidine at 8 mL/h was initiated in the recovery room. The psoas infusion was subsequently changed to 0.2% bupivacaine without clonidine and the rate increased to 10 mL/h. Supplemental analgesia with oral acetaminophen 1 g every 4 to 6 hours alternating with intravenous ketorolac 15 mg every 6 hours provided satisfactory analgesia, with visual analog scale (VAS) scores of 0 to 2 at rest and 3 to 4 with movement. The psoas catheter was removed 48 hours postoperatively because of prolongation of the prothrombin time. VAS scores remained 0 to 3 throughout the remainder of her hospitalization. CONCLUSION: A multimodal approach consisting of continuous lumbar plexus (psoas) block and nonopioid analgesics successfully provided postoperative pain relief in our patient and facilitated her physical rehabilitation after total knee arthroplasty.

Acetaminophen↗

Multimodality treatment of diffuse malignant pleural mesothelioma.

Diffuse malignant pleural mesothelioma (DMPM) is a challenging disease in all of its aspects, from presentation and diagnosis to staging and treatment. Single-modality therapy was the initial approach to this disease. It generally has not been effective in changing the natural history of DMPM. As a result, multimodality regimens involving surgery with radiation, chemotherapy, or immunotherapy delivered regionally or systemically have been evaluated. Randomized controlled studies comparing various strategies are lacking and, thus, the debate continues regarding the effectiveness of different treatment approaches.

Combined Modality Therapy↗

[Twenty-year experience with multimodal treatment of gastric cancer patients in Poland].

BACKGROUND: Poland is among the countries with high morbidity and mortality rates for gastric carcinoma (GC). Differences of GC biology depending on the geographical regions were assumed. In the literature, there are no reports from detailed clinicopathologic studies carried out in large series of GC patients in Poland. METHODS: Based on the prospectively collected data of 3 696 GC patients treated surgically between 1977-1999, potentially significant prognostic factors were analyzed to assess their prognostic value, and their time related distribution during the over 20-year period of the study. RESULTS: The mean age of the patients was 59.0 (SD 11.6) years and ranged from 20 to 93 years. The male-to-female ratio was 2.3. Overall cumulative 5-year survival was 0.28 (for early GC 0.85) and significantly increased over the period of study. Among factors analyzed the depth of invasion, lymph nodes status, tumor size, age, UICC-R classification and ratio of involved to removed lymph nodes are of statistically significant and most important prognostic value. In the over 20-year period of study the rate of diffuse type carcinoma according to Laurén increased, but the tumor locations did not change significantly. The rate of early GC did not change throughout the period of study but number of most advanced cases decreased. Chemo- and chemoimmunotherapy improved outcomes in some groups of patients. CONCLUSIONS: The basic clinicopathologic profile of Polish patients is similar to that reported in Western Europe and Japan, except for significantly higher early GC occurrence in Japan. According to the obtained results the prognosis of GC depends clearly upon the stage of the disease at the time of surgery. The improvement of outcomes during over 20 years of GC study in Poland was due to introducing better diagnosis and routine multimodal treatment.

Adult↗

Multimodality stereotactic approach to the treatment of cystic craniopharyngiomas.

OBJECTIVES: To present the therapeutic reliability of a multimodality stereotactic approach (MSA) to cystic craniopharyngiomas (CPs), combining neuroendoscopy, intracavitary bleomycin and gamma knife (GK) radiosurgery. METHODS: 8 patients with mono- or multicystic CP (7/8 regrowths/recurrence) underwent stereotactic neuroendoscopy and subsequently treatment with intracavitary bleomycin and GK. They were clinically characterized by hypopituitarism (7 cases), visual impairment (7), endocranial hypertension (7), cognitive and behavioral disturbances (3), and cranial nerve deficits or focal signs (3). Concomitant hydrocephalus was observed in 3/8 patients. According to Backlund's classification, the treated CPs were classified as type A (3 cases), type Cc (4 cases) and type Dc (1 case). In all 8 patients, neuroendoscopy allowed evacuation of the cyst and, in multi-cystic CPs, fenestration of the interposed septa so as to create a single communicating cavity. Thus, a single catheter and Ommaya reservoir system was sufficient both for subsequent aspirations and for bleomycin injection (doses of 1.5-3 mg, usually repeated every 7-8 days, with total doses ranging from 3-35 mg). GK radiosurgery was carried out at a later stage on the collapsed cyst in type A forms, while in types Cc and Dc, it was used on the solid nodule on the same day as the neuroendoscopy. RESULTS: The median follow-up period was 42.5 months. Neurological improvement was observed in 8/8 patients. A complete response (reduction of the entire tumor volume > 90 %) was observed in 3/8 cases (type A), a subtotal response (reduction > 50 %) in 4/8 cases (types Cc and Dc), and a partial response (reduction < 50 %) in 1/8 cases (type Cc). Treatment of CP alone led to normalization of the ventricular morphology in the 3 patients with associated hydrocephalus. Transient GK-related visual worsening was recorded in one case only. One patient died because of ventriculitis after repeated shunt replacements. CONCLUSIONS: This MSA seems to be an effective and safe treatment alternative to microsurgery, above all in patients with regrowing/recurrent cystic CPs.

Adolescent↗