A rapid method to increase the number of F1 plants in pea (Pisum sativum) breeding programs.

In breeding programs, a large number of F2 individuals are required to perform the selection process properly, but often few such plants are available. In order to obtain more F2 seeds, it is necessary to multiply the F1 plants. We developed a rapid, efficient and reproducible protocol for in vitro shoot regeneration and rooting of seeds using 6-benzylaminopurine. To optimize shoot regeneration, basic medium contained Murashige and Skoog (MS) salts with or without B5 Gamborg vitamins and different concentrations of 6-benzylaminopurine (25, 50 and 75 µM) using five genotypes. We found that modified MS (B5 vitamins + 25 µM 6-benzylaminopurine) is suitable for in vitro shoot regeneration of pea. Thirty-eight hybrid combinations were transferred onto selected medium to produce shoots that were used for root induction on MS medium supplemented with α-naphthalene-acetic acid. Elongated shoots were developed from all hybrid genotypes. This procedure can be used in pea breeding programs and will allow working with a large number of plants even when the F1 plants produce few seeds.

Developmental etiology for neuroanatomical and cognitive deficits in mice overexpressing Galphas, a G-protein subunit genetically linked to schizophrenia.

Schizophrenia is a widespread psychiatric disorder, affecting 1% of people. Despite this high prevalence, schizophrenia is not well treated because of its enigmatic developmental origin. We explore here the developmental etiology of endophenotypes associated with schizophrenia using a regulated transgenic approach in mice. Recently, a polymorphism that increases mRNA levels of the G-protein subunit Galphas was genetically linked to schizophrenia. Here we show that regulated overexpression of Galphas mRNA in forebrain neurons of mice is sufficient to cause a number of schizophrenia-related phenotypes, as measured in adult mice, including sensorimotor gating deficits (prepulse inhibition of acoustic startle, PPI) that are reversed by haloperidol or the phosphodiesterase inhibitor rolipram, psychomotor agitation (hyperlocomotion), hippocampus-dependent learning and memory retrieval impairments (hidden water maze, contextual fear conditioning), and enlarged ventricles. Interestingly, overexpression of Galphas during development plays a significant role in some (PPI, spatial learning and memory and neuroanatomical deficits) but not all of these adulthood phenotypes. Pharmacological and biochemical studies suggest the Galphas-induced behavioral deficits correlate with compensatory decreases in hippocampal and cortical cyclic AMP (cAMP) levels. These decreases in cAMP may lead to reduced activation of the guanine exchange factor Epac (also known as RapGEF 3/4) as stimulation of Epac with the select agonist 8-pCPT-2'-O-Me-cAMP increases PPI and improves memory in C57BL/6J mice. Thus, we suggest that the developmental impact of a given biochemical insult, such as increased Galphas expression, is phenotype specific and that Epac may prove to be a novel therapeutic target for the treatment of both developmentally regulated and non-developmentally regulated symptoms associated with schizophrenia.

Interventions for replacing missing teeth: hyperbaric oxygen therapy for irradiated patients who require dental implants.

BACKGROUND: Dental implants offer one way to replace missing teeth. Patients who have undergone radiotherapy and those that have also undergone surgery for cancer in the head and neck region may benefit particularly from reconstruction with implants. Hyperbaric oxygen therapy (HBO) has been advocated to improve the success of implant treatment in patients who have undergone radiotherapy but this remains a controversial issue. OBJECTIVES: To compare success, morbidity, patient satisfaction and cost effectiveness of dental implant treatment carried out with and without HBO in irradiated patients. SEARCH STRATEGY: We searched the Cochrane Oral Health Group's Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. Handsearching included several dental journals. We checked the bibliographies of relevant clinical trials and review articles for studies outside the handsearched journals. We wrote to authors of the identified randomised controlled trials (RCTs), to more than 55 oral implant manufacturers; we used personal contacts and we asked on an internet discussion group in an attempt to identify unpublished or ongoing RCTs. No language restriction was applied. The last electronic search was conducted on 13 June 2007. SELECTION CRITERIA: Randomised controlled trials of HBO therapy for irradiated patients requiring dental implants. DATA COLLECTION AND ANALYSIS: Screening of eligible studies, assessment of the methodological quality of the trials and data extraction were conducted in duplicate and independently by two review authors. Results were expressed as random-effects models using mean differences for continuous outcomes and risk ratios for dichotomous outcomes with 95% confidence intervals. MAIN RESULTS: Only one RCT was identified and included. Thirteen patients received HBO therapy while other 13 did not. Two to six implants were placed in fully edentulous mandibles to be rehabilitated with bar-retained overdentures. One year after implant loading four patients died from each group. One patient, treated with HBO, developed an osteoradionecrosis and lost all implants so the prosthesis could not be provided. Five patients in the HBO group had at least one implant failure versus two in the control group. There were no statistically significant differences for prosthesis and implant failures, postoperative complications and patient satisfaction between the two groups. AUTHORS' CONCLUSIONS: Despite the limited amount of clinical research available, it appears that HBO therapy in irradiated patients requiring dental implants may not offer any appreciable clinical benefits. There is a definite need for more RCTs to ascertain the effectiveness of HBO in irradiated patients requiring dental implants. These trials ought to be of a high quality and reported as recommended by the CONSORT statement (http://www.consort-statement.org/). Each clinical centre may have limited numbers of patients and it is likely that trials will need to be multicentred.

Bizarreness of size and shape in dream images.

Bizarreness in dreams is defined as an unusual combination of features in the phenomenal unified consciousness, that is, an incoherent simulation of the waking world. The present study investigated the specific mechanisms underlying dream image production and the phenomenal unity of consciousness by focusing on size and shape bizarreness. Data were derived from a Dream Data Bank of experimental dream studies. Analyses revealed that feature distortion was quite infrequent. Results are discussed in terms of cognitive processes proposed in a dream production model. Theoretical cognitive constructs, such as Kosslyn's imagery model, memory systems functioning, and binding, were used to speculate about these two specific types of bizarreness.

Treatment of vitiligo with the 308 nm excimer laser.

Several therapeutic modalities have been proposed for the treatment of vitiligo either to achive repigmentation in the lesions or to stabilize the disease. Narrow-band UVB therapy has been shown to be effective and safe for use in the management of vitiligo; its wavelength is not so different from 308 nm XeCl excimer laser radiation. We present an open and uncontrolled pilot study of 24 patients (12 men, 12 women) in whom vitiligous patches were treated twice a week, for 9 months with 308 nm XeCl laser radiation. Seven of the 24 patients showed greater than 75% repigmentation, six patients showed repigmentation of between 25 and 75% and six patients showed less than 25% repigmentation. In five patients no signs of repigmentation were noted. The therapeutic benefit was stable during the 12-month follow-up period. Although these results are promising, treatment has so far been limited to small numbers of patients and a short follow-up period. Other prospective studies are needed to assess the efficacy of this treatment modality.

Synthesis and biological evaluation of enantiomerically pure pyrrolyl-oxazolidinones as a new class of potent and selective monoamine oxidase type A inhibitors.

Due to the key role played by monoamine oxidases (MAOs) in the metabolism of neurotransmitters, MAO inhibitors (MAOIs) represent an useful tool for the treatment of several neurological diseases. Among selective MAOIs, MAO-A inhibitors (e.g. clorgyline) are used as antidepressant and antianxiety drugs and are claimed to protect neuronal cells against apoptosis, and selective MAO-B inhibitors (e.g. L-deprenyl) can be used in the treatment of Parkinson's disease either alone or in combination with L-DOPA. However, they engender covalent bonds with the active site of the enzyme and induce irreversible inhibition; moreover, they tend to lose their initial selectivity at high dosages or with repeated administrations. Phenyloxazolidinones belong to third-generation-MAOIs, characterized by a selective and reversible inhibition of the enzyme. Among these molecules, the most representative are toloxatone and befloxatone, two selective and reversible MAO-A inhibitors used in therapy as antidepressant drugs. Going on our searches on CNS potentially active compounds containing a pyrrole moiety we prepared 3-(1H-pyrrol-1-yl)-2-oxazolidinones (1) and isomeric 3-(1H-pyrrol-2-and -3-yl)-2-oxazolidinones (2 and 3) as anti-MAO agents. Such derivatives resulted selective and reversible MAO-A inhibitors. The most potent compound is (R)-5-methoxymethyl-3-(1H-pyrrol-1-yl)-2-oxazolidinone (1b), endowed with very high potency (K(iMAO-A) = 4.9 nM) and A-selectivity (A-selectivity = 10,200, about 116-fold greater than that of befloxatone).

Interventions for replacing missing teeth: hyperbaric oxygen therapy for irradiated patients who require dental implants.

BACKGROUND: Dental implants offer one way to replace missing teeth and associated tissues. Patients who have undergone radiotherapy and those that have also undergone surgery for cancer may benefit particularly from reconstruction with implants. Hyperbaric oxygen therapy (HBO) has been advocated to improve the success of implant treatment in patients who have undergone radiotherapy but this remains a controversial issue. OBJECTIVES: This review aims to compare success, morbidity, patient satisfaction and cost effectiveness of dental implant treatment carried out with and without HBO in irradiated patients. SEARCH STRATEGY: The Cochrane Oral Health Group Specialised Register, the Cochrane Controlled Trials Register, MEDLINE and EMBASE were searched. In addition, the bibliographies of review articles were checked for studies outside the handsearched journals and personal references were searched. We also wrote to implant manufacturers and experts in the field. SELECTION CRITERIA: Randomised controlled trials of HBO therapy for irradiated patients requiring dental implants. DATA COLLECTION AND ANALYSIS: No randomised trials were identified. MAIN RESULTS: No data were available. REVIEWER'S CONCLUSIONS: Clinicians ought to make patients aware of the lack of reliable clinical evidence for or against the clinical effectiveness of HBO in irradiated patients requiring dental implants. There is a definite need for RCTs to ascertain the effectiveness of HBO in irradiated patients requiring dental implants. These trials ought to be of a high quality and reported as recommended by the CONSORT statement (http://www.consort-statement.org/). Each clinical centre may have limited numbers of patients and it is likely that trials will need to be multi-centred.

Activity in human frontal cortex associated with spatial working memory and saccadic behavior.

We examined, with event-related fMRI, two hypotheses about the organization of human working memory function in frontal cortex: (1) that a region immediately anterior to the frontal eye fields (FEF) (superior frontal cortex, SFC) is specialized for spatial working memory (Courtney, et al., 1998); and (2) that dorsolateral prefrontal cortex (PFC) plays a privileged role in the manipulation of spatial stimuli held in working memory (Owen, et al., 1996; Petrides 1994). Our delayed-response task featured 2-D arrays of irregularly arranged squares that were highlighted serially in a random sequence. The Forward Memory condition required maintenance of the spatio-temporal sequence, the Manipulate Memory condition required reordering this sequence into a new spatially defined order, the Guided Saccade condition required saccades to highlighted squares in the array, but no memory, and the Free Saccade condition required self-paced, horizontal saccades. The comparison of fMRI signal intensity associated with 2-D saccade generation (Guided Saccades) versus fMRI signal intensity associated with the delay period of the working memorials condition revealed no evidence for greater working memory-related activity than saccade-related activity in SFC in any individual subject, nor at the level of the group, and greater 2-D saccade than delay-period activity in three of five subjects. These results fail to support the hypothesis that spatial working memory-related activity is represented preferentially in a region of SFC anterior to the FEF (Courtney, et al., 1998). The comparison of maintenance versus manipulation of spatio-temporal information in working memory revealed significantly greater activity associated with the latter in dorsolateral PFC, but not in ventrolateral PFC or in SFC. These results suggest that the delay-related function of SFC is limited to the maintenance of spatial information, and that this region does not support the nonmnemonic executive control functions supported by dorsolateral PFC. These results also indicate that the preferential recruitment of dorsolateral PFC for the manipulation of information held in working memory applies to tasks employing spatial stimuli, as well as to tasks employing verbal stimuli (D'Esposito, et al., 1999); Petrides et al., 1993; Postle et al., 1999).

Hepatocellular carcinoma treated with chemoembolization: assessment with contrast-enhanced doppler ultrasonography.

PURPOSE: To report our preliminary experience concerning the use of Doppler ultrasonography (DUS) techniques after intravenous injection of the galactose-based contrast agent Levovist in the assessment of hepatocellular carcinoma (HCC) treated with transcatheter arterial chemoembolization (TACE). The sonographic findings are correlated with those obtained using iodized oil (Lipiodol) helical computed tomography (CT). METHODS: For 7 months we studied 28 patients with cirrhosis and HCC (a total of 43 nodules) who had undergone TACE between 18 and 30 days previously. The lesions were investigated with color Doppler ultrasonography (CDUS) and power Doppler ultrasonography (PDUS), before and after infusion of the echo-contrast agent (300 mg/ml, maximum 1 injection for each nodule, administered at constant velocity within 60-90 sec), and with helical Lipiodol-CT (0-7 days after DUS). In the retrospective analysis, special attention was given to the Doppler signals related to pulsatile intra- and perinodular flow and to the detection of new vessels after contrast agent injection. The signal intensity was graded as 0 (absent), 1 (low), 2 (medium), or 3 (high), while its distribution was classified as peripheral, central, or diffuse. Oily agent retention on CT scans was assessed as 0 (absent), I (<10%), II (<50%), III (>50%), or IV (homogeneous). These scores were awarded separately, without knowledge of the other judgments. RESULTS: An hepatic global echo-enhancing effect was identified in all cases and always lasted long enough to allow an accurate analysis of all parenchymal lesions (at least 8 min). The signal scores could be evaluated in 39 of 43 HCCs, as follows: basal CDUS: grade 0 in 17 lesions, grade 1 in 16, grade 2 in 6; contrast-enhanced CDUS: grade 0 in 12 lesions, grade 1 in 10, grade 2 in 14, grade 3 in 3; basal PDUS: grade 0 in 15 lesions, grade 1 in 13, grade 2 in 9, grade 3 in 2; contrast-enhanced PDUS: grade 0 in 11 lesions, grade 1 in 9, grade 2 in 15, grade 3 in 6. Lipiodol-CT scoring was: grade 0 in 1 lesion, grade I in 7, grade II in 11, grade III in 9, grade IV in 11. In all but one nodule the difference between CDUS and PDUS scores, compared both with each other and with nonenhanced and contrast-enhanced examinations, was never greater than one grade. CONCLUSIONS: Contrast-enhanced DUS is a simple and fast procedure allowing a valuable, constant echo-enhancing effect of sufficient duration. DUS techniques, especially contrast-enhanced PDUS, offer an effective and realistic analysis of HCC nodules treated with TACE and show more evident agreement with Lipiodol-CT findings than baseline studies.

[Multiphasic spiral computed tomography in hepatocarcinoma. An evaluation following different percutaneous ablative procedures]. / Tomografia Computerizzata spirale multifasica dell'epatocarcinoma. Valutazione dopo differenti procedure ablative percutanee.

PURPOSE: To report our personal experience with helical CT evaluation of hepatocellular carcinoma treated with various percutaneous interventional procedures. We assessed both nodular response and the spectrum of changes within normal parenchyma. MATERIAL AND METHODS: December 1996 to September 1998 we examined with helical CT 41 patients (73 nodules in all) with hepatocellular carcinoma treated with percutaneous ablation therapies: conventional ethanol injection in 18 subjects (31 nodules), one-shot ethanol injection in 3 (8 nodules), radiofrequency thermal ablation in 16 (25 nodules), and combined chemoembolization and ethanol injection in 4 (9 nodules). CT performed was 4-27 days after the last session, acquiring biphasic volumetric images in 14 patients and triphasic volumetric images in 27. A second treatment with subsequent CT study was performed for 28 lesions; 15 underwent 3 serial studies and 6 underwent 4 studies. RESULTS: Compared with pretreatment findings, the diameter was unchanged in 62% of the nodules and increased in 38%. Morphology was unchanged in 63% of the lesions while in 37% a mild deformation toward the needle path or a more regular and round shape was evident. Borders were unchanged in 37% of the cases and modified in 63%, appearing well-defined in 73% and ill-defined in 27%. The necrotic portion had a low attenuation with a nodule-to-parenchyma gradient more evident on delayed than on venous and finally arterial acquisitions; 8% of the lesions were not recognizable on unenhanced scans. Residual viable tissue was identified in 44% of the nodules and quantified as 100% in 1% of all lesions, > 75% in 3%, > 50% in 4%, > 25% in 12%, < 25% in 23%. It was located centrally in 6% of the cases, peripherally in 12%, and eccentrically in 81%, and the shape was crescent in 66% of the cases, oval in 19%, and different in 16%. During the arterial phase the residual tumor appeared hyperdense in 97% of the nodules and isodense in 3%, while during the portal phase it was hyperdense in 22%, isodense in 28% and hypodense in 50%, and during the delayed phase hypodense in 100%. For what concerns the uninvolved parenchyma, lobar atrophy was present in 4% of the nodules, segmental atrophy in 8%, and subsegmental in 16%; caval thrombosis was found in 1 patient, portal thrombosis in 4. Arterioportal fistulas were identified in 5% of the nodules and areas of transient inhomogeneous attenuation in several cases. Subsegmental biliary dilation was detected in 4% of the lesions. CONCLUSION: Multiple-phase helical CT allows optimal depiction of primitive liver nodules treated with percutaneous interventional procedures and has a central role in the assessment of tumor response. Accurate is also the evaluation of changes or complications involving the surrounding parenchyma. Regarding the ablation effect, two typical features can be identified: after total necrosis nodular volume is unchanged or increased, borders are well-defined, and density is low and homogeneous (especially in delayed phases), while after partial necrosis the diameter is not modified, margins are ill-defined, attenuation is less decreased, and peripheral tumor maintains high density in arterial phase and low density in delayed phases. As for the treatment procedure, we found that thermal ablation with radiofrequency and single-session ethanol injection cause more evident alterations within both nodule and hepatic parenchyma, while after multi-session ethanol injection changes are less dramatic and consequently more difficult to assess.

Left prefrontal activation during episodic remembering: an event-related fMRI study.

The major current theory relating brain mechanisms in prefrontal cortex (PFC) to memory for discrete events (episodic memory) emphasizes the role of right PFC during retrieval. Using event-related fMRI, we found both right and left PFC activity during episodic remembering, but only the left PFC activity was related to the amount of episodic detail required at test. We suggest that right PFC subserves relatively simple, heuristic, cognitive processes and that left PFC is recruited for more reflectively demanding, systematic, processes. Episodic remembering often requires such systematic processes and, under those circumstances, recruits left, as well as right, PFC.

[The correlation between Doppler echography with a contrast medium and CT in the study of a hepatocarcinoma submitted to chemoembolization]. / Correlazione tra ecografia Doppler con mdc e TC nello studio dell'epatocarcinoma sottoposto a chemioembolizzazione.

PURPOSE: We report our preliminary experience concerning Doppler studies with the intravenous injection of a galactose-based echo contrast agent (SHU 508 A) in hepatocellular carcinomas (HCCs) treated with transcatheter arterial chemoembolization. We correlated US findings with those of iodized-oil helical CT. MATERIAL AND METHODS: In 1997 we examined 18 patients with cirrhosis and HCC (31 nodules in all) submitted to hepatic oily chemoembolization 15-30 days earlier. The lesions were studied with color and power Doppler US before and after echo contrast agent infusion (300 mg/mL, injection/nodule, constant rate in 60-90 s) and with Lipiodol CT (0-7 days after US). In the retrospective analysis, special care was paid to Doppler signals from pulsatile intra- and perinodular flow and to the detection of new small vessels on enhanced images. The signal was graded as absent (0), weak (1), medium (2) and strong (3). The oily agent uptake on CT images was graded as absent (0), grade I (< 10%), II (< 50%), III (> 50%) and homogeneous (IV). All scores were given on a blind basis. RESULTS: Liver enhancement was found in all cases and always lasted long enough to allow the accurate depiction of parenchymal lesions (at least 8 minutes). Signal intensity could be evaluated in 27 of 31 HCCs (2 were too deeply seated and two were too affected by cardiac activity). We had the following scores: basal color Doppler: grade 0 = 15 lesions, grade 1 = 8 lesions, grade 2 = 4 lesions; contrast-enhanced color Doppler: grade 0 = 11 lesions, grade 1 = 7 lesions, grade 2 = 8 lesions, grade 3 = 1 lesion; basal power Doppler: grade 0 = 12 lesions, grade 1 = 8 lesions, grade 2 = 6 lesions, grade 3 = 1 lesion; contrast-enhanced power Doppler: grade 0 = 10 lesions, grade 1 = 7 lesions, grade 2 = 8 lesions, grade 3 = 2 lesions; Lipiodol-CT: grade 0 = 1 lesion, grade I = 1 lesion, grade II = 7 lesions, grade III = 8 lesions, grade IV = 10 lesions. The difference between color and power Doppler scores, both compared to each other and between basal and enhanced images, never exceeded one. CONCLUSIONS: Contrast-enhanced Doppler US is a simple and fast technique allowing strong, constant and long-lasting enhancement. Doppler US techniques permit the effective and realistic study of HCC nodules treated with chemoembolization and show a better correlation with Lipiodol CT than basal studies. Power Doppler is slightly more sensitive and accurate than color Doppler and shows a better correlation with Lipiodol CT.

Activity of high dose 24 hour 5-fluorouracil infusion plus L-leucovorin in advanced colorectal cancer.

BACKGROUND: Modulation of 5-fluorouracil (5-FU) by leucovorin (L-LV) in patients (pts) with advanced colorectal cancer has been demonstrated to produce a highly significant benefit over single-agent 5-FU in terms of tumor response rate, but this advantage does not translate into an evident improvement of overall survival. To improve the clinical efficacy of the 5-FU plus L-LV regimen a phase II study of weekly 24-hour high-dose 5-FU infusion with L-LV was undertaken. PATIENTS AND METHODS: Seventy advanced colorectal patients were enrolled and treated by a weekly outpatient combination regimen according to the following schedule: L-LV 100 mg/sqm by 4 hours i.v. infusion followed by 5-FU 2600 mg/sqm over a 24 hours infusion combined with a fixed dose of oral L-LV (50 mg) every 4 hours for 5 times. Forty-four pts did not receive any previous CT and 26 pts were pretreated with fluoropyrimidines. RESULTS: The overall objective response rate (OR) was 35.3%; 7 CR and 11 PR (42.8% OR) were observed in the group of untreated pts, and 6 PR (23% OR) were reported among previously treated pts. Major side effects were represented by diarrhoea (grade III: 26%, grade IV: 1%), hand-foot syndrome (grade III: 4%, grade IV: 1%) and mucositis (grade III: 4%); however, this did not significantly influence the therapeutic programme. Median 5-FU dose intensity was 100% and 80% at 4 weeks, 87% and 75% at 8 weeks in untreated and pretreated pts, respectively. CONCLUSIONS: L-Leucovorin modulation of weekly short-term continuous infusion of high-dose 5-fluorouracil appeared a well-tolerated outpatient regimen; it demonstrated a high activity in advanced colorectal cancer, both in untreated pts and in pts resistant to 5-FU-based chemotherapy.

[Lipiodol with and without Gelfoam in primary liver tumors. Plasma levels of Mitoxantrone and clinical results]. / Lipiodolizzazione associata o meno a Gelfoam in pazienti con tumore epatico primitivo. Livelli plasmatici di Mitoxantrone e risultati clinici.

Transcatheter chemoembolization with various drugs is employed for palliative treatment of hepatocellular carcinoma. Thirty-seven patients (33 with Child A or B cirrhosis) were treated with 14 mg/m2 of Mitoxantrone and up to 20 ml of Lipiodol, followed by Gelfoam embolization as indicated. Sixty-nine cycles were given, with mean (+/-SD) Lipiodol and emulsified Mitoxantrone doses of 11.3 +/- 3.8 ml and 11.8 +/- 5.2 mg, respectively. Thirteen, 16, and 8 patients received one, two, and three cycles, respectively, with time intervals of 123 +/- 60 days. Thirty patients had Gelfoam embolization at the first cycle, 9 at the second and 4 at the third. At the first cycle, 10 patients underwent serial measurements of serum Mitoxantrone up to two hours after a full dose of emulsified drug. Drug levels resulted much lower than those reported after plain arterial infusion, with AUC levels (+/-SE) of 5924 +/- 1015 and 4381 +/- 429 ng/ml x 120 min in 6 and 4 cases treated with and without Gelfoam, respectively. No treatment related deaths occurred. Complications were mild and transient, including nausea vomiting in most cases, fever > 38 degrees C 67%, pain 74%, ascites 8% jaundice 3%, bleeding 3%, pancreatitis 3%, myelosuppression 44%, diarrhea 5%. Treatment response rate was 49% (including 16% minor response) with 16% early progressions. With a median follow-up of 12 months, the 12-month response duration and survival rates were 56% and 79% respectively. Transcatheter chemoembolization with Mitoxantrone deserves further evaluation in randomized studies.

A functional MRI study of mental image generation.

The neural substrates of mental image generation were investigated with functional MRI. Subjects listened to words under two different instructional conditions: to generate visual mental images of the words' referents, or to simply listen to each word and wait for the next word. Analyses were performed which directly compared the regional brain activity during each condition, with the goal of discovering whether mental image generation engages modality-specific visual areas, whether it engages primary visual cortex, and whether it recruits the left hemisphere to a greater extent than the right. Results revealed that visual association cortex, and not primary visual cortex, was engaged during the mental image generation condition. Left inferior temporal lobe (Brodmann's area 37) was the most reliably and robustly activated area across subjects, had activity which extended superiorly into occipital association cortex (area 19). The results of this experiment support the hypothesis that visual mental imagery is a function of visual association cortex, and that image generation is asymmetrically localized to the left.

Object recognition difficulty in visual apperceptive agnosia.

Two patients with visual apperceptive agnosia were examined on tasks assessing the appreciation of visual material. Elementary visual functioning was relatively preserved, but they had profound difficulty recognizing and naming line drawings. More detailed evaluation revealed accurate recognition of regular geometric shapes and colors, but performance deteriorated when the shapes were made more complex visually, when multiple-choice arrays contained larger numbers of simple targets and foils, and when a mental manipulation such as a rotation was required. The recognition of letters and words was similarly compromised. Naming, recognition, and anomaly judgments of colored pictures and real objects were more accurate than similar decisions involving black-and-white line drawings. Visual imagery for shapes, letters, and objects appeared to be more accurate than visual perception of the same materials. We hypothesize that object recognition difficulty in visual apperceptive agnosia is due to two related factors: the impaired appreciation of the visual perceptual features that constitute objects, and a limitation in the cognitive resources that are available for processing demanding material within the visual modality.

[Effects of adjuvant hyaluronidase in tumors refractory to chemotherapy. Review of the literature and pharmacokinetics of cisplatin after regional administration in animals and humans]. / Effetto della ialuronidasi adiuvante in tumori refrattari alla chemioterapla. Revisione della letteratura e farmacocinetica del cisplatino dopo somministrazione regionale nell'animale e nell'uomo.

Several clinical studies have recently suggested that topical or systemic adjuvant hyaluronidase may increase the therapeutic index of anticancer drugs. In cases of disease progression, further objective responses have been observed after the association of hyaluronidase to the previously employed drugs. Some evidences suggest that hyaluronidase improves local diffusion as well as tissue and tumor uptake of the associated drugs. Hence, plasma and tissue concentrations of platinum following administration of cisplatin alone and associated with hyaluronidase have been investigated in 20 rats after intraperitoneal injection and in 10 patients with colorectal liver metastases and local progression of the disease after regional and systemic chemotherapy with intraarterial cisplatin and intravenous 5-fluorouracil. Three out of six refractory patients treated with hepatic intraarterial cisplatin + hyaluronidase showed one minor response and two stable diseases, respectively, without any apparent increase of treatment related toxicity. In turn, adjuvant hyaluronidase increased both the extent distribution and lasting time of cisplatin in the body and reduced plasma levels of total and free platinum originating from cisplatin, without any modification of either unbound fraction of platinum or total body clearance. Hence, adjuvant hyaluronidase seems to increase tissue extraction of cisplatin and, particularly, liver extraction after intraarterial administration in man. These results encourage further studies aimed to determine the clinical role of adjuvant hyaluronidase in patients refractory to regional chemotherapy.