First report of the damaging pest Meloidogyne enterolobii parasitizing mulberry (Morus alba L.) in Vietnam.

Mulberry (Morus alba L.) is highly important crop in Vietnam, playing a key role in the country's economy through sericulture, food supply, pharmaceuticals, and beverage industries (Nguyen et al., 2018; Rohela et al., 2020). Recently, many mulberry-growing areas in Lam Dong, Vietnam have reported severe symptoms associated with nematode infection, including yellowing leaves, stunted growth, and severe root galling, leading to a significant decline in mulberry productivity. From April to December 2022, twenty soil and root samples from mulberry-growing areas in Lam Dong (Da Teh: 11°28'48.11"N; 107°28'23.74"E elevation: 133m; Lam Ha 11°48'25.13"N; 108°14'7.13"E elevation: 848m) were collected to uncover the presence of Meloidogyne enterolobii parasitizing mulberry in Vietnam. One nematode population was randomly selected for characterizing in this study among analyzed nematode populations. Females were extracted from heavily galled roots (Fig. S1) from a single mulberry tree in Lam Dong, Vietnam, using a needle and forceps (Subbotin et al., 2021). The perineal patterns of adult females (n = 10) have an oval shape, with clearly visible phasmids, along with a prominently high and squared dorsal arch. The striae are smooth and coarse, while the perivulval region remains devoid of striae. The lateral lines appear indistinct, and the tail tip is easily observable. Morphometric measurements were as follows: body length = 585 ± 78 (464-724) µm, body width = 367 ± 75 (271-529) µm, neck length = 221.5 ± 30.7 (167-269.6) µm, stylet length = 13.1 ± 1.2 (11.4-15.1) µm, vulva-slit length 16.3±2.3 (10.4-18) µm, vulva-anus distance = 16.8±3.0 (11.4-18) µm, anus-tail tip distance = 10.3±2.1 (6.9-14.2) µm, interphasmidial distance = 15.9 ± 3.7 (10.3-23.4) µm. The morphology of this nematode population is highly in agreement with the original description of M. enterolobii (Yang & Eisenback, 1983). This population was also identified using the D2-D3 of 28S rRNA and 18S rRNA (Powers et al., 2017; Subbotin et al., 2006) regions. The D2-D3 of 28S rRNA sequences from this study (accession numbers: OR889633) exhibited 99.5-99.8% similarity to the sequences of M. enterolobii from GenBank (accession numbers: OR214950 and ON496981). While the 18S rRNA sequences (accession numbers: OR896547) showed 99.2-99.3% similarity to the sequences of M. enterolobii from GenBank (accession numbers: MZ955995, MZ531901, and MW488150). To carry out Koch's postulates, 2000 J2s from collected M. enterolobii egg masses (initial population) were inoculated on two-month-old plantlets of mulberry (n = 6), planted on 2L pots within a screenhouse, non-inoculated plantlets (n=6) served as negative controls. After 90 days post-inoculation, nematode reproduction factors (RF = final density (nematodes were extracted from the whole root system and corresponding soil samples (Subbotin et al., 2021)) / initial population) and root damage symptoms were evaluated. The inoculated plantlets exhibited consistent yellowing leaves, stunting, and root galling symptoms (Fig. S1), mirroring observations from the field, with an average RF of 11.5. Control plants displayed no symptoms. Root-knot nematodes extracted from the roots were identified as M. enterolobii through molecular analyses of D2-D3 of 28S and 18S rRNA regions (GenBank accession numbers: OR889634 (D2-D3 of 28S) and OR896548 (18S)), thereby confirming that mulberry acts as a host for M. enterolobii. Currently, this nematode has been reported to be associated with two different host plants, including guava (Trinh et al., 2022) and pomelo (Le et al., 2023). Our discovery marks the first documented case of Meloidogyne enterolobii parasitizing mulberry in Vietnam. While the impact on mulberry productivity remains to be really important for sericulture food supply, pharmaceuticals, and beverage industries; the aggressive nature of M. enterolobii, as observed in the field and confirmed by the screenhouse tests, raises concerns about potential economic losses in mulberry production. Therefore, further investigations are needed to assess the extent of M. enterolobii infestation in mulberry orchards and to develop effective control measures to safeguard the sustainability of mulberry cultivation in Vietnam.

Morphological and molecular characterizations of Pratylenchus coffeae infecting Ming aralia and coffee in Vietnam.

Pratylenchus coffeae, belonging to the root-lesion nematode group, is a highly prevalent and destructive plant-parasitic nematode that is able to infest a wide range of host plants. Although this species' devastating impacts on coffee plantations across the world are widely known on other host plants, its association with Ming aralia has never been reported. Our study characterized two popu lations of P. coffeae (associated with Ming aralia and coffee) and compared them with other popu lations from previous studies in Vietnam and other countries in the world. The identification of P. coffeae in our study was confirmed by the comprehensive analysis encompassing morphological examination, morphometric data, and molecular characterizations of the COI mtDNA and D2D3 of 28S rRNA regions. The cluster and MDS analyses revealed that the two populations of P. coffeae from Vietnam are closely related to those from Japan and Indonesia. The D2-D3 sequences of 28S rRNA and COI mtDNA regions exhibited high similarity among these populations, indicating a stable genetic profile. Our research contributes to a better understanding of the distribution and genetic characterizations of P. coffeae by offering new morphological and molecular insights into the presence of this nematode in Vietnam. Additionally, this nematode species was found to be associated with host plant's symptoms such as chlorotic leaves, stunted growth and root lesion in both hosts. Given the economic significance of both Ming aralia and coffee crops in Vietnam, as well as the damaging potential of P. coffeae, this study emphasizes the need of proactive nematode management measures to control this destructive pest.

A machine learning analysis of a "normal-like" IDH-WT diffuse glioma transcriptomic subgroup associated with prolonged survival reveals novel immune and neurotransmitter-related actionable targets.

BACKGROUND: Classification of primary central nervous system tumors according to the World Health Organization guidelines follows the integration of histologic interpretation with molecular information and aims at providing the most precise prognosis and optimal patient management. According to the cIMPACT-NOW update 3, diffuse isocitrate dehydrogenase-wild type (IDH-WT) gliomas should be graded as grade IV glioblastomas (GBM) if they possess one or more of the following molecular markers that predict aggressive clinical course: EGFR amplification, TERT promoter mutation, and whole-chromosome 7 gain combined with chromosome 10 loss. METHODS: The Cancer Genome Atlas (TCGA) glioma expression datasets were reanalyzed in order to identify novel tumor subcategories which would be considered as GBM-equivalents with the current diagnostic algorithm. Unsupervised clustering allowed the identification of previously unrecognized transcriptomic subcategories. A supervised machine learning algorithm (k-nearest neighbor model) was also used to identify gene signatures specific to some of these subcategories. RESULTS: We identified 14 IDH-WT infiltrating gliomas displaying a "normal-like" (NL) transcriptomic profile associated with a longer survival. Genes such as C5AR1 (complement receptor), SLC32A1 (vesicular gamma-aminobutyric acid transporter), MSR1 (or CD204, scavenger receptor A), and SYT5 (synaptotagmin 5) were differentially expressed and comprised in gene signatures specific to NL IDH-WT gliomas which were validated further using the Chinese Glioma Genome Atlas datasets. These gene signatures showed high discriminative power and correlation with survival. CONCLUSION: NL IDH-WT gliomas represent an infiltrating glioma subcategory with a superior prognosis which can only be detected using genome-wide analysis. Differential expression of genes potentially involved in immune checkpoint and amino acid signaling pathways is providing insight into mechanisms of gliomagenesis and could pave the way to novel treatment targets for infiltrating gliomas.

Post-treatment Mortality Among Patients With Tuberculosis: A Prospective Cohort Study of 10 964 Patients in Vietnam.

BACKGROUND: Tuberculosis is the leading infectious cause of death. Steep reductions in tuberculosis-related mortality are required to realize the World Health Organization's "End Tuberculosis Strategy." However, accurate mortality estimates are lacking in many countries, particularly following discharge from care. This study aimed to establish the mortality rate among patients with pulmonary tuberculosis in Vietnam and to quantify the excess mortality in this population. METHODS: We conducted a prospective cohort study among adult patients treated for smear-positive pulmonary tuberculosis in 70 clinics across Vietnam. People living in the same households were recruited as controls. Participants were re-interviewed and their survival was established at least 2 years after their treatment with an 8-month standardized regimen. The presence of relapse was established by linking identifying data on patients and controls to clinic registries. Verbal autopsies were performed. The cumulative mortality among patients was compared to that among a control population, adjusting for age and gender. RESULTS: We enrolled 10964 patients and 25707 household controls. Among enrolled tuberculosis patients, 9% of patients died within a median follow-up period of 2.9 years: 342 (3.1%) during treatment and 637 (5.8%) after discharge. The standardized mortality ratio was 4.0 (95% confidence interval 3.7-4.2) among patients with tuberculosis, compared to the control population. Tuberculosis was the likely cause of death for 44.7% of these deceased patients. CONCLUSIONS: Patients treated for tuberculosis had a markedly elevated risk of death, particularly in the post-treatment period. Interventions to reduce tuberculosis mortality must enhance the early detection of drug-resistance, improve treatment effectiveness, and address non-communicable diseases.

Characterization and Genetic Structure of a Tospovirus Causing Chlorotic Ring Spots and Chlorosis Disease on Peanut; Comparison with Iranian and Polish Populations of Tomato yellow fruit ring virus.

A Tospovirus species was isolated from peanut plants showing chlorotic ring spots and chlorosis, and identified as Tomato yellow fruit ring virus (TYFRV) on the basis of its biological, serological, and molecular properties. In host range studies, a broad range of indicator plants was infected by the five isolates studied; all the isolates systemically infected Nicotiana tabacum cultivars and, thus, they were classified into the N-host-infecting type isolates of the virus. These isolates strongly reacted with TYFRV antibodies but not with the specific antibodies of other tospoviruses tested. Recombination analyses showed that the nucleoprotein gene of the peanut isolates and other isolates studied were nonrecombinant. In phylogenetic trees, the virus isolates were clustered in three genogroups: IRN-1, IRN-2, and a new group, POL; the peanut isolates fell into IRN-2 group. Multiple sequence alignments showed some genogroup-specific amino acid substitutions among the virus isolates studied. The results revealed the presence of negative selection in TYFRV populations. Also, the Iranian populations had higher nucleotide diversity compared with the Polish population. Genetic differentiation and gene flow analyses indicated that the populations from Iran and Poland and those belonging to different genogroups were partially differentiated populations. Our findings seem to suggest that there has been frequent gene flow between some populations of the virus in the mid-Eurasian region of Iran.

Management of diabetes in Indigenous communities: lessons from the Australian Aboriginal population.

Type 2 diabetes mellitus and other chronic cardio-metabolic conditions are significant contributors to the large disparities in life expectancy between Indigenous and non-Indigenous Australians. Type 2 diabetes is more prevalent from a young age among Indigenous Australians and is often preceded by a cluster of risk factors, including central obesity, dyslipidaemia, albuminuria and socio-economic disadvantage. Management of type 2 diabetes in Australian Indigenous peoples can be challenging in the setting of limited resources and socio-economic disadvantage. Key strategies to address these challenges include working in partnership with patients, communities and primary healthcare services (PHC, Aboriginal community controlled and government services) and working in a multidisciplinary team. Population prevention measures are required within and beyond the health system, commencing as early as possible in the life course.

Patients' beliefs and behaviors related to treatment adherence in patients with asthma requiring maintenance treatment in Asia.

OBJECTIVES: To identify patients' beliefs or behaviors related to treatment adherence and to assess association between asthma control and adherence in Asian patients with asthma. METHODS: We conducted a cross-sectional observational study of adult patients with asthma from specialist clinics in six Asian countries. Patients who were deemed by their treating physicians to require a maintenance treatment with an inhaler for at least 1 year were recruited. Patients completed a 12-item questionnaire related to health beliefs and behaviors, the 8-item Morisky Medication Adherence Scale (MMAS-8), the Asthma Control Test (ACT™), and the Standardized Asthma Quality of Life Questionnaire (AQLQ-S). RESULTS: Of the 1054 patients recruited, 99% were current users of inhaled corticosteroids. The mean ACT score was 20.0 ± 4.5 and 64% had well-controlled asthma. The mean MMAS-8 score was 5.5 ± 2.0 and 53% were adherent. Adherence was significantly associated with patients' understanding of the disease and inhaler techniques, and with patients' acceptance of inhaler medicines in terms of benefits, safety, convenience, and cost (p < 0.01 for all). In multivariate analysis, three questions related to patients' acceptance of inhaler medicines remained significantly associated with poor adherence, after adjusting for potential confounders: "I am not sure inhaler type medicines work well" (p = 0.001), "Taking medicines more than once a day is inconvenient" (p = 0.002), and "Sometimes I skip my inhaler to use it over a longer period" (p < 0.001). CONCLUSIONS: Our study showed that patients' acceptance of the benefits, convenience and cost of inhaler medications have a significant impact on treatment adherence in the participating Asian countries.

Data on consumers' purchase behavior towards certified rice in Vietnam.

The data presented in this article capture purchase behavior of certified rice of 199 urban Vietnamese consumers, surveyed in August 2016. The dataset captures behavioral outcomes in terms of rice purchase as well as factors that affect purchase behavior such as psychological and socio-economic determinants. The data not only contribute to generating a better understanding of the drivers of purchase behavior towards certified rice, but also provide insights into the inclusiveness of consumer access to food safety for staple crops such as rice in Vietnam. Our data and survey instrument may serve as a reference for other developing countries with a similar context and facing similar challenges.

Incidence of Infection of Enterovirus 71 and Coxsackieviruses A6 and A16 among Household Contacts of Index Cases in Dong Thap Province, Southern Vietnam.

BACKGROUND: Scarce information exists about immunity to hand, foot, and mouth disease (HFMD) among household contacts of index cases in Vietnam and what that means for reducing ongoing HFMD transmission in the community. METHODS: We analyzed neutralizing antibodies (NT) and the incidence of enterovirus (EVs) infection among household contacts of index cases in a province where HFMD remains endemic. Throat swab and 2 mL blood samples from household contacts were collected at enrollment, during and after 2 weeks follow-up. RESULTS: The incidence of EV-A71 infection among household contacts was 40/84 (47.6%, 95% Cl: 36.9-58.3%), compared with 106/336 (31.5%, 95% Cl: 26.6-36.5%) for CV-A6 and 36/107 (33.6%, 95% Cl: 24.7-42.6%) for CV-A16. The incidence of CV-A6 infection was fairly constant across ages; in contrast, CV-A71 and CV-A16 had some variation across ages. At baseline, higher geometric mean titer (GMT) of EV-A71, CV-A6, and CV-A16 antibody titers was found for 25-34-year groups (range 216.3 to 305.0) compared to the other age groups. There was a statistically significant difference in GMT values of CV-A6 and CV-A16 between those who had an infection or did not have infection among households with an index case of these serotypes. CONCLUSIONS: Our results indicated that adults were becoming infected with HFMD and could be contributing to the transmission. There is, therefore, a need for considering the household setting as an additional target for intervention programs for HFMD.

Correlates of HIV-1 viral suppression in a cohort of HIV-positive drug users receiving antiretroviral therapy in Hanoi, Vietnam.

Injection drug users bear the burden of HIV in Vietnam and are a focus of national treatment programmes. To date, determinants of successful therapy in this population are unknown. Substance use and clinical correlates of viral suppression were studied in 100 HIV-1-infected drug users receiving antiretroviral therapy (ART) for at least six months in Hanoi, Vietnam. The mean age of the cohort was 29.9 + 4.9 years; all were men. A majority of patients (73%) achieved viral suppression (HIV-RNA <1000 copies/mL). Correlates of viral suppression include self-reported > or = 95% adherence (P < 0.01) and current use of trimethoprim/sulphamethoxazole (P < 0.01); current or ever diagnosed with tuberculosis was associated with viral non-suppression (P = 0.006). Tobacco use was prevalent (84%), and surprisingly 48% of patients reported active drug use; neither was associated with viral non-suppression. This is the first study to document successful ART treatment in a population of Vietnamese drug users; rates of viral suppression are comparable to other international populations. The 28% of patients without HIV-1 suppression highlight the need for adherence promotion, risk reduction programmes, and population-based surveillance strategies for assessing the emergence of HIV drug resistance in settings where access to viral load and drug resistance testing is limited.

The role of DNA methylation in expression of the p19/p16 locus in human bladder cancer cell lines.

Methylation of CpG sites in the control regions of tumor suppressor genes may be an important mechanism for their heritable, yet reversible, transcriptional inactivation. These changes in methylation may impair the proper expression and/or function of cell cycle regulatory genes and confer a selective growth advantage to affected cells. Detailed methylation analysis using genomic bisulfite sequencing was performed on a series of subclones of a bladder cancer cell line in which a hypermethylated p16 gene had been reactivated by transient treatment with 5-aza-2'-deoxycytidine. Methylation of the CpG island in the promoter of the p16 gene in human bladder cancer cells did not stop the formation of a transcript initiated 20 kb upstream by the p19 promoter but did prevent the expression of a p16 transcript. Furthermore, we show that reactivant clones that expressed p16 at varying levels contained heterogeneous methylation patterns, suggesting that p16 expression can occur even in the presence of a relatively heavily methylated coding region. We also present the first functional evidence that methylation of only a small number of CpG sites can significantly down-regulate p16 promoter activity, thus providing support for the model of progressive inactivation of this tumor suppressor gene by DNA methylation.

Defects at center P underlie diabetes-associated mitochondrial dysfunction.

Detailed respiration studies on isolated liver mitochondria from streptozotocin-induced diabetic Sprague-Dawley rats revealed a disease-associated decrease in the ADP/O ratio, a marker for mitochondrial ability to couple the consumption of oxygen to the phosphorylation of ADP. This decrease was observed following induction of respiration with glutamate/malate, succinate, or duroquinol, which enter the electron transport chain selectively at complexes I (NADH dehydrogenase), II (succinate dehydrogenase), or III (cytochrome bc1 complex), respectively. These data, coupled with studies using respiratory inhibitors (most importantly antimycin A and myxothiazol), localize at least a portion of this defect to a single site within the electron transport chain (center P in the Q-cycle portion of complex III). These results suggest that liver mitochondria from diabetic animals may generate increased levels of reactive oxygen species at the portion of the electron transport chain already established as the major site of mitochondrial free radical generation. The reduction in the ADP/O ratio occurred in mitochondria that do not have overt defects in the respiratory control ratio or in State 3 and State 4 respiration. The data in this paper suggest that defects in center P of the electron transport chain likely increase mitochondrial exposure to oxidants in the diabetic. This data may partially explain the evidence of altered exposure and/or response to reactive species in mitochondria from diabetics. This work thus provides further clues to the interaction between oxidative stress and diabetes-associated mitochondrial dysfunction.

Pontine glioma extending to the ipsilateral cavernous sinus and Meckel's cave: MR appearance.

The authors describe an exophytic glioma of the pons that grew into the Meckel's cave and cavernous sinus in a 75-year-old man. Pontine gliomas should be included in the differential diagnosis of a hyperintense, complex cystic mass seen along the distribution of cranial nerve V.

Cystic acoustic schwannomas: MR characteristics.

PURPOSE: To evaluate the spectrum of MR characteristics of cystic acoustic schwannoma and to investigate its incidence. METHODS: We retrospectively reviewed the MR findings and clinical records of 16 patients with cystic acoustic schwannomas. In addition, the MR examinations of 411 consecutive patients referred for clinical suspicion of acoustic schwannomas were reviewed retrospectively to assess the incidence of acoustic schwannomas with cystic lesions arising from the internal auditory canal. RESULTS: Of the 16 acoustic schwannomas with MR evidence of intramural cysts, 11 tumors had single small cysts, and five had multiple intramural cysts of variable size. Intramural cysts in 11 of the 16 tumors exhibited higher signal intensity than that of cerebrospinal fluid; the remainder were isointense to cerebrospinal fluid on both T1- and T2-weighted images. All intramural cysts showed circumferential enhancement after contrast administration. Nine of the 16 cystic acoustic schwannomas also had MR evidence of extramural/arachnoid cysts. Six of the extramural/arachnoid cysts had epicenters away from the dural interface, and the other three cysts were broadly based against the dura. The incidence of cystic acoustic schwannomas was 11.3% and association with extramural/arachnoid cysts 7.5%. CONCLUSION: Our series suggests that cystic changes in acoustic schwannomas and the association with extramural/arachnoid cysts are not as rare as previously reported by other diagnostic methods. The high signal intensity of intramural cysts is probably related to necrotic material, blood, or colloid-rich fluid. The difference in the MR characteristics of extramural/arachnoid cysts associated with acoustic schwannomas and those of typical arachnoid cysts not associated with neoplasia may be related to higher protein and/or colloid contents secreted by the tumor. Most extramural/arachnoid cysts had epicenters between the tumor and brain, suggesting that the most likely mechanism of formation is peritumoral adhesions. It creates a pseudo-duplication caused by the trapping of fluid between the leptomeninges and the mass, resulting in an acquired type of arachnoid cyst.

The effect of contrast dose, imaging time, and lesion size in the MR detection of intracerebral metastasis.

PURPOSE: To evaluate the effect of MR contrast dose versus delayed imaging time on the detection of metastatic brain lesions based on lesion size. METHODS: Contrast MR examinations with gadoteridol were obtained in 45 patients with brain metastases. The patients were divided into two groups: 16 received cumulative standard dose (0.1 mmol/kg) and 29 received cumulative triple dose (0.3 mmol/kg). Both groups were evaluated at two dose levels (lower dose and higher dose) with two separate injections. Each patient received an initial bolus injection of either 0.05 (cumulative standard dose) or 0.1 (cumulative triple dose) mmol/kg of gadoteridol to reach the lower-dose level and underwent imaging immediately and 10 and 20 minutes later. Thirty minutes after injection, an additional bolus injection of 0.05 (cumulative standard dose) or 0.2 (cumulative triple dose) mmol/kg was administered to reach the cumulative higher-dose level (cumulative standard dose, 0.1 mmol/kg; cumulative triple dose, 0.3 mmol). Images were acquired immediately. RESULTS: There was no difference in the detection rate for lesions larger than 10 mm among T2-weighted, lower-dose immediate and delayed, or immediate higher-dose images in both study groups. Lesions smaller than 10 mm had improved detection with delayed imaging in both study groups; however, the immediate higher-dose studies still had the highest detection rate. CONCLUSION: In the evaluation of small central nervous system metastases, either delayed imaging after the injection of standard contrast dose or higher contrast dose may improve their detection, and therefore affect clinical management. Higher contrast dose (cumulative triple dose) studies appear to be more effective than delayed imaging with standard dose.

MR of fetal central nervous system abnormalities.

PURPOSE: To investigate whether MR can provide additional information on fetuses with central nervous system abnormalities as demonstrated by ultrasonography. METHODS: Fetal MR examinations were studied prospectively in 22 pregnant women whose fetuses showed evidence of anomalies on ultrasound performed in the High-Risk Obstetric Clinic. RESULTS: In 19 of 22 cases, postpartum confirmatory diagnoses were obtained by MR or CT examinations, autopsy, or surgery. In general, the image quality of MR is comparable with that of ultrasound. However, in six of 22 cases (27%), MR provided additional information that altered the ultrasound diagnosis; these included cases of infarction, diastematomyelia, normal hemimegalencephaly with early myelination, Dandy-Walker variant, and lipoma. All of these cases had postpartum confirmation. The additional information changed the treatment in three of six patients (no intervention or elective abortion). CONCLUSIONS: In certain situations MR can add valuable information to that obtained by sonography in the evaluation of the fetal central nervous system.

Sequential MR enhancement pattern in normal pituitary gland and in pituitary adenoma.

PURPOSE: To measure and evaluate the temporal enhancement characteristics of the normal pituitary gland and pituitary adenoma. METHODS: Thirty healthy subjects and 10 patients with sellar pituitary adenomas were studied prospectively using dynamic MR imaging with a 5- or 10-sec temporal resolution during a bolus injection of gadolinium. RESULTS: Qualitative visual analysis demonstrated a consistent sequential pattern of pituitary enhancement in which the posterior lobe enhanced earlier than the anterior lobe by approximately 35 sec. Quantitative analysis revealed that posterior lobe enhancement occurred 9.8 +/- 1.5 sec (mean +/- SEM) before the anterior lobe in healthy subjects, whereas tumor enhancement occurred significantly before the anterior lobe but only slightly before the posterior lobe in patients with adenomas. CONCLUSION: The sequential enhancement pattern of the normal pituitary gland was found to be consistent with its vascular anatomy. In contrast to previous reports, pituitary adenomas were found to enhance earlier than the anterior lobe. These results suggest that pituitary adenomas have a direct arterial blood supply, similar to that of the posterior pituitary lobe.

Delineation of gliomas with various doses of MR contrast material.

PURPOSE: To examine the effects of different gadolinium doses on the delineation of gliomas, particularly the demonstration of abnormal enhancement on T1-weighted images extending beyond the zone of apparent signal abnormality on corresponding T2-weighted images. METHODS: During phase II clinical trials of gadoteridol, 23 patients with pathologically proved gliomas were studied by MR with various doses of gadoteridol, ranging from 0.05 to 0.3 mmol/kg. RESULTS: All of the gliomas were readily detected by T2-weighted images. Twelve of 23 patients demonstrated enhancement on T1-weighted images extending beyond the zone of apparent signal abnormality demonstrated on T2-weighted images. These findings were seen in none of the six patients (0%) studied at 0.05 mmol/kg, one of five patients (20%) studied at 0.1 mmol/kg, four of five patients (80%) studied at 0.2 mmol/kg, and seven of seven patients (100%) studied at 0.3 mmol/kg. CONCLUSIONS: The detection of symptomatic gliomas does not require a contrast agent because they are generally large and readily demonstrated on T2-weighted images. However, the area of postcontrast enhancement of gliomas seems to be greater with higher doses of contrast agent. The cause of the abnormal enhancement extending beyond the zone of apparent signal abnormality on T2-weighted images seen in this limited study is unknown and probably represents tumor infiltration. The frequency of detection of such findings appears to be proportional to the dose of contrast material used.

Cost-effectiveness of high-dose MR contrast studies in the evaluation of brain metastases.

PURPOSE: To investigate the cost-effectiveness of high-dose MR contrast studies in the management of brain metastases. METHODS: During the phase III clinical trial of high-dose contrast studies (0.3 mmol/kg), 11 of 27 patients were judged by the reviewers to have potential treatment changes based on the additional information provided by the high-dose studies. We retrospectively evaluated how many of these 27 patients had actual treatment changes because of the results of the high-dose study. Using the fee schedule at our institution, the cost-effectiveness was analyzed based on the cost savings from treatment changes and the additional expense of implementing the high-dose studies. RESULTS: A total of 3 craniotomies ($22,800 each) and 2 aggressive courses of radiation therapy ($1122 each) were avoided in 4 patients because of the additional lesions detected by the high-dose studies. This resulted in a treatment cost savings of $70,644. The extra expense for implementing the high-dose study is $9126 for a single injection in all 27 patients, $9295 for 2 separate injections completed in 1 visit in the 11 patients, and $11,154 for 2 separate injections completed in 2 separate visits. The cost savings in management (diagnosis and treatment) therefore ranged from $59,490 to $61,518 for all patients and from $2203 to $2278 per patient. CONCLUSION: Based on our limited data, the high-dose study seems to impact positively on the cost-effectiveness in the management of brain metastases. However, because our study had limitations, our results need to be confirmed with a larger patient population and a more standardized treatment approach and fee schedule.

Crystal structure of 180 degree K of bis-3, 5-diisopropylsalicylatobisdimethylsulfoxidozinc(II) and the inhibition of seizures and polymorphonuclear leukocyte chemiluminescence.

Dimethylsulfoxide (DMSO) formed a ternary complex when mixed with a Zn-3, 5-diisopropylsalicylate complex of unknown structure. The structure of this new ternary complex was characterized in an initial effort to understand the nature of this compound. Since the original complex is known to have anticonvulsant activity, the new ternary complex was also examined for anticonvulsant activity. The original complex was examined for inhibition of the polymorphonuclear leukocyte (PMNL) respiratory burst in an effort to mechanistically account for zinc complex mediated anticonvulsant activity. Dissolving the structurally unknown complex in DMSO gave crystals of a characterizable complex with an empirical formula C30H46O8S2Zn. Crystallographic data: P 1, Z = 2, a = 8.06(1), b = 12.452(2), c = 17.951(2) A, alpha = 74.42(l), beta = 77.07(1), gamma = 89.50(1) degree. The structure was refined to R = 0.03, RW = 0.04 for 3815 independent reflections with I > 2 sigma(I). This complex is mononuclear, with two 3,5-diisopropylsalicylate ligands and two bonded DMSO ligands, Zn(II)(3,5-DIPS)2(DMSO)2, Zn(II) is coordinate covalently bonded to four O atoms in a strongly distorted tetrahedral arrangement. Each DMSO ligates via its sulfoxide O atom while each 3,5-diisopropylsalicylate ligand is monodentate The non-ligating carbonyl O atom of each 3,5-DIPS is free except for an intramolecular hydrogen bond from the hydroxy group of the same ligand. Both 3,5-DIPS acid and Zn(II)(3,5-DIPS)2(DMSO)2 were examined for anticonvulsant activity in the Maximal Electroshock (MES) and Metrazol (MET) models of seizures and found to prevent both types of seizures. The Zn complex was qualitatively and quantitatively more effective than treatment with the free ligand. The influence of a Zn 3,5-DIPS complex and of the ligand 3,5-DIPS on PMNL oxidative metabolism was also studied to help understand the mechanism of anticonvulsant activity of these compounds. A dose-related and significant decrease in chemiluminescent (CL) response to opsonized Zymosan was observed, and the Zn complex was significantly more effective than the free ligand. It is concluded that mononuclear Zn complexes have anticonvulsant activity in Grand Mal and Petit Mal models of seizure possibly due to inhibition of the synthesis of superoxide or down-regulation of Nitric Oxide Synthase in activated phagocytic cells of the central nervous system.