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Introduction and Objective: It remains unknown whether the use of nephron sparing intervention (NSI) is impacted with delayed intervention after a period of active surveillance (AS) compared with immediate intervention for patients with clinically localized renal masses ≤7cm (cT1RMs). We hypothesized that the proportion of patients undergoing NSI is similar among patients undergoing immediate and delayed intervention for cT1RMs., Methods: We retrospective reviewed the prospectively maintained Michigan Urological Surgery Improvement Collaborative (MUSIC) registry for patients undergoing intervention for cT1RMs from 05/2017 to 09/2023. The primary outcome was type of treatment received: radical nephrectomy (RN) or NSI (partial nephrectomy, ablation, or stereotactic body radiation therapy). The main independent variable was timing of treatment: immediate (treatment within 90 days) vs. delayed intervention (>90 days). We fit a mixed-effects multivariable logistic regression model to assess for the adjusted association of immediate vs delayed intervention with the receipt of NSI and estimate an adjusted probability of NSI., Results: We identified 2,156 patients, of whom 93% underwent immediate intervention and 7% underwent a period of AS prior to delayed intervention. Median time from initial visit to intervention was 1.4 (IQR 0.9-2.0) and 13 (IQR 7.7-21) months in the immediate vs delayed intervention groups, respectively. In the multivariable model, we did not appreciate a significant association between delayed intervention with receipt of NSI (OR 0.99, 95% CI 0.57-1.70, P >0.9). The adjusted proportion of NSI was 75% and 78% for patients in the immediate and delayed intervention cohorts, respectively., Conclusion: Patients undergoing delayed intervention after AS had similar use of NSI compared with those undergoing immediate intervention. Active surveillance for patients with cT1RMs does not appear to compromise the ability to perform nephron sparing interventions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Monica Van Til reports financial support was provided by Blue Cross Blue Shield of Michigan. Alice Semerjian reports financial support was provided by Blue Cross Blue Shield of Michigan. Mahin Mirza reports financial support was provided by Blue Cross Blue Shield of Michigan. Craig G. Rogers reports financial support was provided by Blue Cross Blue Shield of Michigan. Brian R. Lane reports financial support was provided by Blue Cross Blue Shield of Michigan. Kevin Ginsburg reports was provided by Blue Cross Blue Shield of Michigan. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Archaea are vital components of the human microbiome, yet their study within the gastrointestinal tract (GIT) is limited by the scarcity of cultured representatives. Our study presents a method for the targeted enrichment and isolation of methanogenic archaea from human fecal samples. The procedure combines methane breath testing, in silico metabolic modeling, media optimization, FACS, dilution series, and genomic sequencing through Nanopore technology. Additional analyzes include the co-cultured bacteriome, comparative genomics of archaeal genomes, functional comparisons, and structure-based protein function prediction of unknown differential traits. Successful establishment of stable archaeal cultures from 14 out of 16 fecal samples yielded nine previously uncultivated strains, eight of which are absent from a recent archaeome genome catalog. Comparative genomic and functional assessments of Methanobrevibacter smithii and Candidatus Methanobrevibacter intestini strains from individual donors revealed features potentially associated with gastrointestinal diseases. Our work broadens available archaeal representatives for GIT studies, and offers insights into Candidatus Methanobrevibacter intestini genomes' adaptability in critical microbiome contexts., (© 2024. The Author(s).)

Language is a potential source of predictors for suicidal thoughts and behaviors (STBs), as changes in speech characteristics, communication habits, and word choice may be indicative of increased suicide risk. We reviewed the current literature on STBs that investigated linguistic features of spoken and written language. Specifically, we performed a search in linguistic, medical, engineering, and general databases for studies that investigated linguistic features as potential predictors of STBs published in peer-reviewed journals until the end of November 2021.We included 75 studies that investigated 279,032 individuals with STBs (age = 29.53 ± 10.29, 35% females). Of those, 34 (45%) focused on lexicon, 20 (27%) on prosody, 15 (20%) on lexicon and first-person singular, four (5%) on (morpho)syntax, and two (3%) were unspecified. Suicidal thoughts were predicted by more intensifiers and superlatives, while suicidal behaviors were predicted by greater usage of pronouns, changes in the amount of verb usage, more prepend and multifunctional words, more nouns and prepositions, and fewer modifiers and numerals. A diverse field of research currently investigates linguistic predictors of STBs, and more focus is needed on their specificity for either suicidal thoughts or behaviors., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Social isolation and loneliness are associated with morbidity and mortality in older adults. Limited evidence exists regarding which interventions improve connectedness in this population., Design/setting/participants: In this pre-post study we assessed community-based group health class participants' (age ≥50) loneliness and social isolation. Participants (n = 382) were referred by a Cedars-Sinai Medical Network (Los Angeles, California) healthcare provider or self-referred from the community (July 2017-March 2020)., Intervention: Participants met with a program coordinator and selected Arthritis Exercise, Tai Chi for Arthritis, EnhanceFitness, or the Healthier Living Workshop., Measurements: We measured social isolation using the Duke Social Support Index (DSSI) and loneliness using the UCLA 3-item Loneliness Scale at baseline, class completion, and 6 months., Results: Mean age was 76.8 years (standard deviation, SD = 9.1); 315 (83.1%) were female; 173 (45.9%) were Non-Hispanic white; 143 (37.9%) were Non-Hispanic Black; 173 (46.1%) lived alone; mean baseline DSSI score was 26.9 (SD = 4.0) and mean baseline UCLA score was 4.8 (SD = 1.8). On multivariable analysis adjusted for gender, race/ethnicity, income, self-rated health, and household size, DSSI improved by 2.4% at 6-week compared to baseline (estimated ratio, ER: 1.024; 95% confidence interval [CI]: 1.010-1.038; p-value = 0.001), and 3.3% at 6-month (ER: 1.033; 95% CI: 1.016-1.050; p-value <0.001). UCLA score after adjusting for age, gender, race/ethnicity, live alone, number of chronic conditions, income, and self-rated health, did not change at 6-week (ER: 0.994; 95% CI: 0.962-1.027; p-value = 0.713), but decreased by 6.9% at 6-months (ER: 0.931; 95% CI: 0.895-0.968; p-value <0.001)., Conclusion: Community-based group health class participants reported decreased loneliness and social isolation at 6-month follow-up., (Copyright © 2020 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Purpose: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common functional gastrointestinal disorder. Probiotics and synbiotics have been shown to improve symptoms of IBS, although mechanisms of action are currently not understood., Methods: We investigated the effects of a 4-week oral synbiotic treatment (OMNi-BiOTiC ® Stress Repair) in ten IBS-D patients on gastrointestinal mucosal and fecal microbiota, mucosa-associated immune cells, and fecal short-chain fatty acids. The upper and lower gastrointestinal tracts were compared before and after a 4-week synbiotic treatment using endoscopic evaluation to collect mucosal specimens for FACS analysis and mucosal 16S rRNA gene analysis. In stool samples, analysis for fecal SCFAs using GC-MS, fecal zonulin using ELISA, and fecal 16S rRNA gene analysis was performed., Results: Synbiotics led to an increased microbial diversity in gastric (p = 0.008) and duodenal (p = 0.025) mucosal specimens. FACS analysis of mucosal immune cells showed a treatment-induced reduction of CD4 + T cells (60 vs. 55%, p = 0.042) in the ascending colon. Short-chain fatty acids (acetate 101 vs. 202 µmol/g; p = 0.007) and butyrate (27 vs. 40 µmol/g; p = 0.037) were elevated in fecal samples after treatment. Furthermore, treatment was accompanied by a reduction of fecal zonulin concentration (67 vs. 36 ng/ml; p = 0.035) and disease severity measured by IBS-SSS (237 vs. 54; p = 0.002)., Conclusions: Our findings indicate that a short-course oral synbiotic trial may influence the human gastrointestinal tract in IBS-D patients on different levels which are region specific.

Population-level adaptation to spatial variation in factors such as climate and soils is critical for climate-vulnerability assessments, restoration seeding, and other ecological applications in species management, and the underlying information is typically based on common-garden studies that are short duration. Here, we show >20 yr were required for adaptive differences to emerge among 13 populations of a widespread shrub (sagebrush, Artemisia tridentata ssp wyomingensis) collected from around the western United States and planted into common gardens. Additionally, >10 yr were required for greater survival of local populations, that is, local adaptation, to become evident. Variation in survival was best explained by the combination of populations' home ecoregion combined with grouping of minimum temperature and aridity. Additional reductions in survival were explained by ungrouped (i.e., continuous) measures of garden-to-population-origin separation in geographic distance (5% decrease in survival per 100 km increase in separation; R 2  = 0.22) and especially in minimum temperature in younger plants (-4% per + °C difference, R 2  = 0.56 vs. 0.29 in the 14th vs. 27th post-planting years, respectively). Longer-term common garden studies are needed. While we await them, uncertainty in adaptive variation resulting from short-term observations could be quantitatively estimated and reported with seed-transfer guidelines to reduce risks of introducing maladapted provenances in restoration., (© 2018 by the Ecological Society of America.)

The initiative described here aims to identify quality indicators (QIs) germane to the international practice of primary care providers (PCP) in post-acute and long-term care in order to demonstrate the added value of medical providers in nursing homes (NHs). A 7-member international team identified and adapted existing QIs to the AMDA competencies for medical providers. QI sources included the ACOVE 3 Quality Indicators (2007), NH Quality Indicators (2004), NH Residential Care Quality Indicators (2002), and AGS Choosing Wisely (2014). We recruited a technical expert panel (TEP) consisting of 11 panelists from the US, Canada, and the European Union, selected for their knowledge and leadership in post-acute and long-term care. The TEP, using a RAND Modified Delphi approach, provided pre-meeting ratings, discussed items in-person for clarification, and re-rated items following discussion. When panelists rated more than 1 option for a particular QI as valid and feasible, the most stringent option was selected for inclusion in the final candidate set of QIs. Panelists confidentially rated an initial 103 items on validity and feasibility of implementation. During the meeting, panelists added 18 QIs and modified 18. In post-meeting analysis, we eliminated 7 QIs rated not valid and 9 QIs for which a more stringent QI was rated valid and feasible. This resulted in a final set of 97 QIs rated valid and feasible and 8 rated valid but not feasible. This set of QIs for PCPs in the NH identified practices in which provider engagement adds value through expertise in geriatric syndromes, employing evidence-based practice, advocating for residents, delivering person-centered care, facilitating advance care planning, and communicating effectively to coordinate care. Next steps include pilot testing and evaluating the association between adherence to QIs, PCP staffing models, and better outcomes., (Published by Elsevier Inc.)

Background: Pain is a multidimensional condition of multiple origins. Determining both intensity and underlying cause are critical for effective management. Utilization of painkillers does not follow any guidelines relying on biomarkers, which effectively eliminates objective treatment. The aim of this study was to evaluate the use of serum cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) as pain biomarkers. This work could significantly advance the diagnosis and treatment of pain., Methods: We assessed the potential utility of serum COX-2 and iNOS as objective measures of pain in a sample of American patients. Pain was scaled between level 0-5 in accordance with the level reported by the patients. Blood samples were collected from 102 patients in the emergency room. Sandwich ELISA was used to determine the COX-2 and iNOS levels in the blood serum while statistical analysis was performed using Pearson product-moment correlation coefficients, Regression and Receiver Operating Characteristics (ROC) analyses. The biomarker results were also compared with self-reports of pain by the patients using conventional pain ratings and patients were asked to report the cause of the pain. Pain levels were clustered into four groups as 0 [self-reported 0], 1 [self-reported as 1], 2 [self-reported as 2 and 3] and 3 [self-reported as 4 and 5]. Co-expression of COX-2 and iNOS could significantly alter pain development and its sensitization. Therefore, iNOS dependent COX-2 levels were employed as categorized level., Results: Self-reported pain levels did not show a correlation with the serum level of COX-2 and iNOS. The lack of correlation is attributed to multiple reasons including patients' intake of painkillers prior to participation, painkiller intake habit, chronic diseases, and subjectivity of self-reported pain. Increased serum COX-2 levels were reported in relation to the subtypes of these health issues. Further, 83% of the patients who reported pain also showed the presence of COX-2 in serum, while only 53% of the patients showed the presence of iNOS in serum. Moderate relation was found between the clustered pain level and categorized COX-2 and iNOS- levels., Conclusions: The findings support the requirement of further studies to use COX-2 and iNOS as prognostic biomarkers for objective quantification of pain at the clinical level., (Copyright © 2018. Published by Elsevier B.V.)

Objective: To investigate immune cells of the colonic mucosa and fecal short-chain fatty acids (SCFAs) in treatment-naive patients with a clinically isolated syndrome (CIS) or early relapsing MS., Methods: In this cross-sectional proof-of-concept study, we obtained mucosal specimens during ileocolonoscopy from 15 untreated patients with CIS/MS and 10 controls. Mucosal immune cells were analyzed by FACS, and gas chromatography-mass spectrometry measurements of stool samples served to determine SCFA., Results: The number of total dendritic cells (DCs), CD103+ tolerogenic DCs, and CD4+25+127-regulatory T cells (Tregs) was significantly reduced in the distal colon of patients with CIS/MS compared with controls, whereas we found no differences in the proximal colon. The patients' fecal samples also showed a substantially lower content of SCFA and especially lower levels of butyrate and acetate., Conclusions: Our findings indicate a disturbed homeostasis of colonic DCs and Tregs in patients with MS which could be associated with colonic SCFA depletion. Although not implying causality, these findings confirm parallel abnormalities of the gut in MS and warrant further research if modulation of the colonic SCFA profile or the colonic Treg pool can serve to modify the course of MS.

T-cell prolymphocytic leukemia is a very rare neoplasm, peaking in the seventh decade. An extensive search failed to find any report of this malignancy in the pediatric population. The malignant cell is morphologically characterized by a high nucleocytopasmic ratio, condensed chromatin, a single nucleolus, and nongranular basophilic cytoplasm. Cells are usually positive for the α/β and only rarely to the γ/δ T-cell receptors. Most patients follow an aggressive clinical course, only some respond to anti-CD52. We present a 6-year-old boy with T-cell prolymphocytic leukemia. The malignant cells expressed a postthymic immunophenotype (CD4/CD8) and positivity for the γ/δ T-cell receptors. The child died after 8 months despite aggressive chemotherapy, anti-CD52, and an allogeneic bone marrow transplant.

Motivation: It has been proposed that clustering clinical markers, such as blood test results, can be used to stratify patients. However, the robustness of clusters formed with this approach to data pre-processing and clustering algorithm choices has not been evaluated, nor has clustering reproducibility. Here, we made use of the NHANES survey to compare clusters generated with various combinations of pre-processing and clustering algorithms, and tested their reproducibility in two separate samples., Method: Values of 44 biomarkers and 19 health/life style traits were extracted from the National Health and Nutrition Examination Survey (NHANES). The 1999-2002 survey was used for training, while data from the 2003-2006 survey was tested as a validation set. Twelve combinations of pre-processing and clustering algorithms were applied to the training set. The quality of the resulting clusters was evaluated both by considering their properties and by comparative enrichment analysis. Cluster assignments were projected to the validation set (using an artificial neural network) and enrichment in health/life style traits in the resulting clusters was compared to the clusters generated from the original training set., Results: The clusters obtained with different pre-processing and clustering combinations differed both in terms of cluster quality measures and in terms of reproducibility of enrichment with health/life style properties. Z-score normalization, for example, dramatically improved cluster quality and enrichments, as compared to unprocessed data, regardless of the clustering algorithm used. Clustering diabetes patients revealed a group of patients enriched with retinopathies. This could indicate that routine laboratory tests can be used to detect patients suffering from complications of diabetes, although other explanations for this observation should also be considered., Conclusions: Clustering according to classical clinical biomarkers is a robust process, which may help in patient stratification. However, optimization of the pre-processing and clustering process may be still required.

Regulatory T cells (Tregs) as key players of the immune system are exposed to numerous triggers including exogenous and endogenous factors. Autonomous nerve activity, melatonin, hormones such as vitamin D and glucocorticoids as well as the exposure to sunlight and microorganisms shape our immunological profile. The complexity of this system is highlighted by the power of each single trigger but more impressive by influencing each others function and potentials directly and indirectly. However, while monocausal correlations of single triggers on Tregs have been studied at length, there is much less known about the impact of numerous coexistent triggers on the dynamics of Treg activity. It can be hypothesized that the dynamics of Treg activity plays a crucial role for the control of our immune system. Therefore it is of the utmost importance that a new translational, multi- and interdisciplinary approach finds its way into future research efforts, which should lead to a more comprehensive and holistic view on the complex immunoregulatory mechanisms and to act in the sense of public health., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Fatigue among medical residents is a well-known and widely discussed phenomenon that has generated much debate., Objective: We wanted to evaluate self-reported fatigue and sleep deprivation, as well as some of the major consequences that have been identified in the period after the medical residents'strike in 2000., Design: A cross sectional study., Participants: Seventy-six medical residents at Soroka university medical centre, who were asked to answer a questionnaire about their personal lives and fatigue level. DATA AND RESULTS: The average work-week was 68.1 +/- 12.4 hours. Residents reported 6.0 +/- 1.3 hours of sleep per night on a regular day and an average of 1.1 +/- 0.5 hours during a 24-hour on-call shift. The ESS score was 11.5 +/- 5.4 points. The number of hours worked per week correlated significantly with the ESS score. Of the residents who drove after a night shift, 29.3% reported falling asleep at least once while driving, and 13.9% of drivers reported that they were involved in a motor vehicle accident., Conclusions: In view of these results, we express a deep concern for the future of Israeli medical residents and their patients. We call upon the authorities to develop appropriate working conditions that will ensure the safety of patients and residents.

Background: Iron deficiency anemia (IDA) is the most common hematologic disorder worldwide. Measures to prevent IDA in infants have been successful with questionable sustainability., Aim: To evaluate the incidence of developing IDA in the second year of life, in infants who were nonanemic at the age of 1 year on routine blood test., Methods: Blood samples were obtained from 193, 24-month-old toddlers, from 2 large clinics of both main sectors in Southern Israel, comparable for lower economic status. IDA was defined as hemoglobin < 11 gr% and microcytosis as mean corpuscular volume < 70 fL., Results: IDA was detected in 8 of 118 Bedouins (5 males) and in 10 of 75 Jewish (6 males) infants (P < 0.01). The probability of a nonanemic child to develop IDA in the second year of life for the whole study population was 9.3% (18 of 193 infants) and significantly higher in the Jewish population (13.3.0% vs. 6.8%, P < 0.01)., Conclusions: Given the difficulty of toddlers to maintain a non-IDA status, and the very low probability of iron overload, our results clearly support the need to continue iron supplementation into the second year.

Objective: The Paducah Gaseous Diffusion Plant (PGDP) became operational in 1952; it is located in the western part of Kentucky. We conducted a mortality study for adverse health effects that workers may have suffered while working at the plant, including exposures to chemicals., Materials and Methods: We studied a cohort of 6820 workers at the PGDP for the period 1953 to 2003; there were a total of 1672 deaths to cohort members. Trichloroethylene (TCE) is a specific concern for this workforce; exposure to TCE occurred primarily in departments that clean the process equipment. The Life Table Analysis System (LTAS) program developed by NIOSH was used to calculate the standardized mortality ratios for the worker cohort and standardized rate ratio relative to exposure to TCE (the U.S. population is the referent for ageadjustment). LTAS calculated a significantly low overall SMR for these workers of 0.76 (95% CI: 0.72-0.79). A further review of three major cancers of interest to Kentucky produced significantly low SMR for trachea, bronchus, lung cancer (0.75, 95% CI: 0.72-0.79) and high SMR for Non-Hodgkin's lymphoma (NHL) (1.49, 95% CI: 1.02-2.10)., Results: No significant SMR was observed for leukemia and no significant SRRs were observed for any disease. Both the leukemia and lung cancer results were examined and determined to reflect regional mortality patterns. However, the Non-Hodgkin's Lymphoma finding suggests a curious amplification when living cases are included with the mortality experience., Conclusions: Further examination is recommended of this recurrent finding from all three U.S. Gaseous Diffusion plants.

The objectives of this study were to carry out cross-cultural adaptation of the HIV/AIDS-Target Quality of Life Instrument for Portuguese and to observe its psychometric properties. Translations, translations synthesis, back translation, analysis by a committee of specialists, pre-final version test, studies of validity and reliability of the final version were carried out. Psychometric properties were evaluated by the administration of the Brazilian version in 50 consecutive HIV positive patients, from the DST/HIV/AIDS municipal ambulatory of São Miguel do Oeste, Santa Catarina State. The internal consistency was observed by a-Cronbach. The reliability was estimated using the intraclass correlation coefficient and Bland-Altmann diagram. The validity was observed comparing the scores of the questionnaire with the WHOQOL-HIV-Brief through the Spearman rank correlation coefficient. The results pointed out to a-Cronbach of 0.893. The correlations obtained were 0.934 for inter-interviewer and 0.977 for intra-interviewer. The correlation with WHOQOL-HIV-Bref was 0.824. It was concluded that the cross-cultural adaptation process was successful and the adapted questionnaire demonstrated good psychometric properties.

This study examines whether structured writing about receiving a diagnosis and treatment for pediatric cancer reduces distress among highly distressed parents of children with cancer (PCWC). Eight PCWC completed measures of posttraumatic stress symptoms (PTSS) and depressive symptoms at two baselines, and again after writing, with 1-month gaps between assessments. Using a guided disclosure protocol (GDP), parents were asked to write about receiving the diagnosis first in a chronological manner, then to explicitly label their emotions at the time of diagnosis and explain the impact of the child's illness on their life. Finally, they were asked to reflect on current feelings, future coping ability, and personal growth. Although symptoms of distress did not change between baselines, significant reductions were found in PTSS from the first baseline to postwriting, but not in depression. This preliminary study suggests that the GDP may reduce PTSS in distressed PCWC.

Objective: To evaluate the sexual behavior of female students enrolled in the Department of Health Science of the Federal University of Paraná and the Department of Biological and Health Scienceof the State University of Paraná at the Cascavel campus., Methods: All the female students, 18 to 24 years of age, enrolled in the above departments in June 2001 were included in the final sample comprised 572 students in Curitiba and 395 in Cascavel. The study evaluated age, family relationship, religiousness, participation in sex education classes and age at initiation of sexual activity. The use of contraceptive methods and condoms, as well as the number of partners, were variables used to evaluate sexual behavior. Safe sex was defined as the use of a condom by monogamous students in all or in the majority of sexual intercourse and the use of condoms by polygamous students during all sexual intercourse. Unsafe sex was defined as the occasional use of condoms by monogamous students and systematic non-use by polygamous students. The data was collected by a self-administered questionnaire. Data analysis was carried out using SPSS and the Pearson and Yates chi-square test, the Wilcoxon-Gehan "p" test, bivariate analysis and logistic regression., Results: There was no statistically significant difference in the risky sexual behavior between students and the city in which they were studying. Around 50% of the students aged 18 to 20 and 70% of those 21 to 24 years of age were sexually active. Abstinence was associated with lower age, greater attendance at religious services and a good relationship between the student and her parents. The practice of safe sex was directly associated with a lower age and living away from home. Participation in sex education classes was associated with greater abstinence but not with safe sex. This relation was not maintained after multivariate analysis., Conclusion: A healthy family relationship and religiousness was associated with safe sexual practices. The percentage of students who still practice unsafe sex is considerable and these results show that being a university student in a health science course does not ensure safe sexual behavior.

The case of an 11-year-old child with adult-type chronic myeloid leukemia, Philadelphia (BCR-ABL) positive, reverse transcription-polymerase chain reaction negative for the major, minor, and micro breakpoints is presented. In the course of 3 years, the child failed to respond to treatment with hydroxyurea, refused all therapy for 6 months, was intolerant to alpha-interferon and progressed, while on imatinib, to acute basophilic leukemia. Subsequently he underwent successful bone marrow transplantation. A secondary cytogenetic clonal evolution, i(17q), developed during hydroxyurea treatment and a tertiary clonal evolution, +8, was detected during imatinib treatment. It is not clear to what extent the several factors (undefined BCR-ABL breakpoint, treatment avoidance, and initial treatment choices, alone or in combination) played a role in the imatinib relapse and resistance and in the disease progression. We conclude that close follow-up with frequent bone marrow sampling is crucial in order to monitor such patients for early relapse and prompt referral for bone marrow transplant.

The diversity of ectomycorrhizal communities associated with Quercus garryana on and off serpentine soils was compared and related to landscape-level diversity. Serpentine soils are high in magnesium, iron, and heavy metals and low in fertility. In plant communities on serpentine soils, a high proportion of flowering plant species are endemic. At three sites with paired serpentine and nonserpentine soils in southwestern Oregon, we sampled Q. garryana roots and categorized ectomycorrhizas by morphotyping and by restriction fragment length patterns. Ectomycorrhizas were abundant at all sites; no single fungal species dominated in the ectomycorrhizas. Of 74 fungal species characterized by morphotype and pattern of restriction fragment length polymorphisms, 46 occurred on serpentine soils, and 32 were unique to serpentine soil. These species are potentially endemic to serpentine soil. Similarities in species composition between paired serpentine and nonserpentine soils were not significantly lower than among three serpentine sites or among three nonserpentine sites. We conclude that mycorrhizal communities associated with oaks on serpentine soil do not differ in species richness or species evenness from those on neighboring nonserpentine soil.

Here we describe a cytogenetic and flow-cytometric study of a case in which a conversion of childhood acute lymphocytic leukemia (ALL) into juvenile myelomonocytic leukemia (JMML) occurred. A 3-year-old boy diagnosed CALLA+, pre-B-ALL with double t(12;21) (by fluorescence in situ hybridization analysis), was treated as per the BFM protocol. A cytogenetic analysis performed at 17 months into treatment showed no t(12;21) in bone marrow (BM) cells; however, a novel translocation, namely, t(4;11), involving the p12 locus on chromosome 4 and the MLL gene at 11q23 was detected in monocytes. No cytogenetic abnormalities were found either in Epstein-Barr virus-transformed B cells or in phytohemagglutinin-stimulated T-lymphoid cells. Flow-cytometric analysis demonstrated an asynchronous expression of the antigenic determinants in populations of granulocytic and monocytoid cells: 60% of monocytes expressed low levels of CD14, an unusually high level of CD15, and no CD13 or HLA-DR antigens; 74% of myeloid cells expressed no CD13. Our results indicate that the transformation from B-cell ALL to JMML in this case occurred most probably in the granulocyte-erythroid-macrophage-megakaryocyte progenitor cells without involving the lymphoid cell line. To date, the child is 10 months off therapy and asymptomatic, with t(4;11) in only 3% of the cells.

Acute idiopathic (immune) thrombocytopenic purpura (ITP) in the pediatric population is a disease in which autoimmune features are mainly self-limited, with a reported mortality of 0.1-0.5%. Major treatment requires intravenous gammaglobulins (i.v. IgG) and corticosteroids. Recently a new globulin, anti-D, has been introduced. The authors have treated 25 children suffering from acute idiopathic thrombocytopenic purpura, with an i.v. anti-D dose of 75 microg/kg as the first treatment. Eligibility criteria included a platelet count < 15,000 and Rh+. Post-treatment response was 76% > 20,000 platelets at 6-10 h and 80% > 50,000 platelets at 48 h; three patients developed chronic idiopathic thrombocytopenic purpura. There were 5/25 patients who did not respond to the initial dose and received i.v. IgG and corticosteroids, 2/5 with a positive response (platelets > 20,000). Side effects consisted of chills (9/25), fever > 38 degrees C (6/25), headache and vomiting (1/25), hemolysis (20/25) from 0.9-6.9 g%, and decrease in hemoglobin levels. One patient needed a blood transfusion after his Hbg decreased from 12.4 to 5.5 g%. The results indicate that anti-D is an effective treatment in acute ITP, but with side effects. Administration of steroids and antipyretics prior to anti-D treatment may prevent the side effects.

O6-alkylguanine-DNA alkyltransferase (AGT) is a DNA-repair protein that reverses the effects of alkylating agents by removing DNA adducts from the O6-position of guanine. We developed a real-time AGT assay that utilizes a fluorescent guanosine analog (3-methylisoxantopterin, 3-MI). 3-MI fluorescence is quenched in DNA and fluorescence intensity increases substantially with digestion of the oligonucleotide and release of 3-MI. The substrate is a doubled-stranded oligonucleotide with 3'-overhangs on each end and a PvuII recognition site. PvuII is inhibited by O6-methylguanine, positioned within the restriction site. 3-MI is incorporated in the opposite strand just outside of the PvuII restriction site. AGT repairs O6-methylguanine; PvuII cleaves at its restriction site, yielding a blunt-ended double strand, which is then digested by exonuclease III. This releases 3-MI from the oligonucleotide, resulting in an increase in fluorescence intensity. All reaction components (100-microL volume) are monitored in a single microcuvette. Rate of increase in fluorescence intensity is related to the amount of AGT in the reaction mixture. We measured AGT levels in extracts from a leukemia cell line, from leukemic lymphoblasts from patients, and from peripheral blood mononuclear cells from normal controls. This method may prove useful for mechanistic studies of AGT.

Background: Patients on parenteral nutrition have an increased incidence of gall bladder sludge and gallstone disease, thought to be related to bile stasis. Intravenous lipid emulsions, especially those containing medium chain triglycerides, have also been shown to have a lithogenic effect on the composition of bile in the gall bladder., Aims: To determine whether lipid infusion influences hepatic bile composition in patients with an indwelling T tube following cholecystectomy and choledochotomy., Methods: In eight patients undergoing the above surgical procedure, the time at which effects of the interrupted enterohepatic circulation were minimal was determined. Twenty two cholesterol gallstone patients with bile fistula were then randomised to receive an infusion of a lipid emulsion containing either long chain triglycerides or a mixture of long and medium chain triglycerides., Results: Lipid infusion resulted in a significant increase in plasma levels of triglycerides and phospholipids. Both lipid emulsions caused an increase in hepatic biliary cholesterol level and cholesterol saturation index, but this effect was more pronounced with medium chain triglycerides. The fatty acid composition of biliary phospholipids showed a significant enrichment of linoleic acid by both lipid infusions., Conclusions: Infusion of triglycerides causes lithogenic changes in hepatic bile composition in humans, the lithogenic effect of infusion of medium chain triglycerides being more pronounced than that of long chain triglycerides. This effect, coupled with gall bladder stasis, may be responsible for the increased risk of biliary sludge and gallstone formation in patients on long term lipid infusion.

Background: Intraventricular chemotherapy results in more uniform drug distribution within the subarachnoid space and allows for more flexible drug administration schedules. The authors report their experience with an intraventricular concentration times time (C x T) chemotherapy regimen for recurrent meningeal leukemia and lymphoma., Methods: Twenty-one patients (median age, 11.6 years) received C x T therapy for meningeal acute lymphoblastic leukemia (n = 18), Burkitt's lymphoma (n = 2), or undifferentiated leukemia (n = 1). Prior therapy included standard intrathecal (IT) methotrexate and cytarabine, cranial or craniospinal radiation (median, 24 Gy), and 0-5 experimental treatment modalities. C x T induction therapy consisted of 2 mg of intraventricular methotrexate administered daily for 3 days every 10 days, for 4 courses. Patients were then consolidated with 4 courses of alternating intraventricular cytarabine (15 mg/day) or methotrexate (2 mg/day) daily for 3 days every 2 weeks (2 courses of methotrexate and 2 courses of cytarabine). Maintenance therapy consisted of alternating monthly courses of C x T methotrexate or cytarabine., Results: Ninety-three percent of patients (14 of 15) who were evaluable for response achieved a complete remission in a median of 10 days (range, 2-40 days). Median remission duration was 15 months. Fourteen patients died of recurrent disease or systemic treatment-related complications; 2 patients are alive, off treatment, and in continuous complete remission for 59+ and 89+ months; 1 patient experienced a meningeal relapse at 24 months on C x T therapy but was reinduced with the C x T regimen, received craniospinal radiation, and is in remission at 142+ months; and 3 are alive with disease at 32+, 72+, and 81+ months. One patient was lost to follow-up., Conclusions: This regimen appears to be an effective and well-tolerated palliative treatment for patients with recurrent meningeal leukemia and lymphoma.

In an attempt to understand the metabolism by the liver of fatty acids (FA) of different chain length, we have studied the incorporation of [1(-14)C]-labeled C2, C8, C10, C12, and C16 into cellular lipids by HepG-2 cells. Over 90% of the radiolabeled FA were detected in phospholipids (PL) and triacylglycerols (TAG). The incorporation of C12 and C16 was three to four times higher than that of C8 and C10 (and reached 35 nmoles per mg protein after 1.5 h). The radioactivity of C2, C8, and C10 was recovered mainly in PL. C12 and C16 were incorporated at approximately equal amounts into PL and TAG. The radioactivity of both C2 and C8 was recovered exclusively in long-chain FA, suggesting oxidation of C8 into C2 units prior to FA synthesis. C10 likewise yielded mainly long-chain FA. However 10% of unchanged C10 was found in PL and up to 30% in TAG. 14C-C12 was largely incorporated unchanged. Under these conditions, the presence of C10 and C12 in PL and TAG was shown also by gas-liquid chromatography. In the presence of either C2, C8, or C10, up to 30% of 14C-monounsaturated FA were detected in PL and TAG. With C12 and C16, the fraction of 14C-monounsaturated FA was much smaller suggesting that extensive desaturation occurred during de novo synthesis.

Five term neonates diagnosed with immune thrombocytopenia were treated with 1 g/kg/day intravenous gamma-globulin. Clinical and laboratory evidence of thrombocytopenia resolved completely in 4 of the 5 patients after a single dose. Only 1 patient received a second dose of the drug. This treatment protocol requires less gamma-globulin than other protocols to safely reduce length of hospitalization.

The response of neonatal tremor to a suckling stimulation test was investigated in 102 healthy neonates born at full term. In 84 the tremor resolved immediately; none had hypocalcaemia and only one had mild hypoglycemia. Eighteen in whom the tremor continued had either hypocalcaemia (n = 13) or hypoglycaemia (n = 5).