Search

Summary:Pharmacokinetic and clinical outcome measures among three groups of patients undergoing hematopoietic transplant were assessed: group A: Parenteral busulfan (Bu) 3.2?mg/kg i.v. given qd, n=20; group B: parenteral Bu 0.8?mg/kg i.v. given every 6?h, n=11; group C: Bu 1?mg/kg p.o. given every 6?h, n=25. All groups received Bu over 4 days followed by Cy 60?mg/kg i.v. qd over 2 days; followed by an infusion of allogeneic stem cells. Median Bu clearance was 3.21?ml/min/kg and median daily AUC was 4071?µmol/min for the group A patients. The dosing formula for Bu i.v. qd was highly predictive of the AUC for patients whose mass?IBW+20%. For patients of greater mass, the dosing formula uniformly resulted in lower-than-predicted AUC. Neurologic toxicity, hepatic toxicity, hematologic engraftment, and relapse at 100 days were comparable across all three groups. Severe AGVHD was least among group A, followed by group B when compared with group C. Bu i.v. qd is a safe and effective regimen for allogeneic transplantation and is at least clinically equivalent to every 6?h dosing schemes using either oral or parenteral Bu.Bone Marrow Transplantation (2005) 35, 747-754. doi:10.1038/sj.bmt.1704871 Published online 7 March 2005 [ABSTRACT FROM AUTHOR]

Hearing loss has been associated with individual cardiovascular disease (CVD) risk factors and, to a lesser extent, CVD risk metrics. However, these relationships are understudied in clinical populations. We conducted a retrospective study of electronic health records to evaluate the relationship between hearing loss and CVD risk burden. Hearing loss was defined as puretone average (PTA 0.5,1,2,4 ) > 20 dB hearing level (HL). Optimal CVD risk was defined as nondiabetic, nonsmoking, systolic blood pressure (SBP) < 120 and diastolic (D)BP < 80 mm Hg, and total cholesterol < 180 mg/dL. Major CVD risk factors were diabetes, smoking, hypertension, and total cholesterol ≥ 240 mg/dL or statin use. We identified 6332 patients (mean age = 62.96 years; 45.5% male); 64.0% had hearing loss. Sex-stratified logistic regression adjusted for age, noise exposure, hearing aid use, and body mass index examined associations between hearing loss and CVD risk. For males, diabetes, hypertension, smoking, and ≥ 2 major CVD risk factors were associated with hearing loss. For females, diabetes, smoking, and ≥ 2 major CVD risk factors were significant risk factors. Compared to those with no CVD risk factors, there is a higher likelihood of hearing loss in patients with ≥ 2 major CVD risk factors. Future research to better understand sex dependence in the hearing loss-hypertension relationship is indicated., (© 2023. The Author(s).)

Across the globe, the legal land rights and tenure of many Indigenous peoples are yet to be recognized. A growing body of research demonstrates that tenure of Indigenous lands improves livelihoods and protects forests in addition to inherently recognizing human rights. However, the effect of tenure on environmental outcomes has scarcely been tested in regions with high development pressure, such as those with persisting forest-agriculture conflicts. In this paper, we conduct an event study and a difference-in-differences analysis to estimate the average treatment effect of land tenure on forest cover change for 129 Indigenous lands in the Atlantic Forest of Brazil from 1985 to 2019. We found that forest outcomes in Indigenous lands improved following tenure compared to pretenure and that forest outcomes improved in tenured compared to nontenured lands. We also found that formalized tenure, rather than incomplete tenure, was necessary to improve forest outcomes. Our study is the first rigorous analysis of the effect of tenure on Indigenous lands in the globally important Atlantic Forest biome and contributes to a growing body of literature on the role of rights-based approaches to conservation. The evidence presented in this study may support efforts to secure the legal rights and autonomy of Indigenous peoples., (© The Author(s) 2023. Published by Oxford University Press on behalf of the National Academy of Sciences.)

Introduction: A relationship between tobacco smoking and hearing loss has been reported; associations with cannabis smoking are unknown. In this cross-sectional population-based study, we examined relationships between hearing loss and smoking (tobacco, cannabis, or co-drug use)., Methods: We explored the relationship between hearing loss and smoking among 2705 participants [mean age = 39.41 (SE: 0.36) years] in the National Health and Nutrition Examination Survey (2011 to 12; 2015 to 16). Smoking status was obtained via questionnaire; four mutually exclusive groups were defined: nonsmokers, current regular cannabis smokers, current regular tobacco smokers, and co-drug users. Hearing sensitivity (0.5 to 8 kHz) was assessed, and two puretone averages (PTAs) computed: low- (PTA 0.5,1,2 ) and high-frequency (PTA 3,4,6,8 ). We defined hearing loss as threshold >15 dB HL. Multivariable logistic regression was used to examine sex-specific associations between smoking and hearing loss in the poorer ear (selected based on PTA 0.5,1,2 ) adjusting for age, sex, race/ethnicity, hypertension, diabetes, education, and noise exposure with sample weights applied., Results: In the age-sex adjusted model, tobacco smokers had increased odds of low- and high-frequency hearing loss compared with non-smokers [odds ratio (OR) = 1.58, 95% confidence ratio (CI): 1.05 to 2.37 and OR = 1.97, 95% CI: 1.58 to 2.45, respectively]. Co-drug users also had greater odds of low- and high-frequency hearing loss [OR = 2.07, 95% CI: 1.10 to 3.91 and OR = 2.24, 95% CI: 1.27 to 3.96, respectively]. In the fully adjusted multivariable model, compared with non-smokers, tobacco smokers had greater odds of high-frequency hearing loss [multivariable adjusted odds ratio = 1.64, 95% CI: 1.28-2.09]. However, in the fully adjusted model, there were no statistically significant relationships between hearing loss (PTA 0.5,1,2 or PTA 3,4,6,8 ) and cannabis smoking or co-drug use., Discussion: Cannabis smoking without concomitant tobacco consumption is not associated with hearing loss. However, sole use of cannabis was relatively rare and the prevalence of hearing loss in this population was low, limiting generalizability of the results. This study suggests that tobacco smoking may be a risk factor for hearing loss but does not support an association between hearing loss and cannabis smoking. More definitive evidence could be derived using physiological measures of auditory function in smokers and from longitudinal studies., Competing Interests: The authors have no relevant financial disclosures or conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The ability to navigate scientific obstacles is widely recognized as a hallmark of a scientific disposition and is one predictor of science, technology, engineering, and mathematics persistence for early-career scientists. However, the development of this competency in undergraduate research has been largely underexplored. This study addresses this gap by examining introductory students' emotional and behavioral responses to research-related challenges and failures that occur in two sequential research-based courses. We describe commonly reported emotions, coping responses, and perceived outcomes and examine relationships between these themes, student demographics, and course enrollment. Students commonly experience frustration, confusion, and disappointment when coping with challenges and failures. Yet the predominance of students report coping responses likely to be adaptive in academic contexts despite experiencing negative emotions. Being enrolled in the second course of a research-based course sequence was related to several shifts in response to challenges during data collection, including less reporting of confusion and fewer reports of learning to be cautious from students. Overall, students in both the first and second courses reported many positive outcomes indicating improvements in their ability to cope with challenge and failure. We assert that educators can improve research-based educational courses by scaffolding students' research trials, failures, and iterations to support students' perseverance.

Objectives: On the basis of the data from school-aged children, there is consistent evidence that there is a prolonged course of auditory development for perceiving speech embedded in competing background sounds. Furthermore, age-related differences are prolonged and pronounced for a two-talker speech masker compared to a speech-shaped noise masker. However, little is known about the course of development during the toddler and preschool years because it is difficult to collect reliable behavioral data from this age range. The goal of this study was to extend our lower age limit to include toddlers and preschoolers to characterize the developmental trajectory for masked speech detection thresholds across childhood., Design: Participants were 2- to 15-year-old children (n = 67) and adults (n = 17), all with normal hearing. Thresholds (71%) were measured for detecting a two-syllable word embedded in one of two maskers: speech-shaped noise or two-talker speech. The masker was presented at 55 dB SPL throughout testing. Stimuli were presented to the left ear via a lightweight headphone. Data were collected using an observer-based testing method in which the participant's behavior was judged by an experimenter using a two-interval, two-alternative testing paradigm. The participant's response to the stimulus was shaped by training him/her to perform a conditioned play-based response to the sound. For children, receptive vocabulary and working memory were measured. Data were fitted with a linear regression model to establish the course of development for each masker condition. Appropriateness of the test method was also evaluated by determining if there were age-related differences in training data, inter-rater reliability, or slope or upper asymptote estimates from pooled psychometric functions across different age groups., Results: Child and adult speech detection thresholds were poorer in the two-talker masker than in the speech-shaped noise masker, but different developmental trajectories were seen for the two masker conditions. For the speech-shaped noise masker, threshold improved by about 5 dB across the age span tested, with adult-like performance being reached around 10 years of age. For the two-talker masker condition, thresholds improved by about 7 dB between 2.5 and 15 years. However, the linear fit for this condition failed to achieve adult-like performance because of limited data from teenagers. No significant age-related differences were seen in training data, probe hit rate, or inter-rater reliability. Furthermore, slope and upper asymptote estimates from pooled psychometric functions were similar across different child age groups., Conclusions: Different developmental patterns were seen across the two maskers, with more pronounced child-adult differences and prolonged immaturity during childhood for the two-talker masker relative to the speech-shaped noise masker. Our data do not support the idea that there is rapid improvement of masked speech detection thresholds between 2.5 and 5 years of age. This study also highlights that our observer-based method can be used to collect reliable behavioral data from toddlers and preschoolers-a time period where we know little about auditory development., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Numerous cardiometabolic factors may underlie risk of hearing loss. Modifiable risk factors such as non-optimal blood pressure (BP) are of interest., Purpose: To investigate early auditory evoked potentials (AEPs) in persons with nonoptimal BP., Research Design: A cross-sectional nonexperimental study was performed., Study Sample: Fifty-two adults (18-55 years) served as subjects. Individuals were classified as having optimal (systolic [S] BP < 120 and diastolic [D] BP < 80 mm Hg, n  = 25) or non-optimal BP (SBP ≥=120 or DBP ≥=80 mm Hg or antihypertensive use, n  = 27). Thirteen subjects had hypertension (HTN) (SBP ≥130 or DBP ≥80 mm Hg or use of antihypertensives)., Data Collection and Analysis: Behavioral thresholds from 0.25 to 16 kHz were collected. Threshold auditory brain stem responses (ABRs) were recorded using rarefaction clicks (17.7/second) from 80 dB nHL to wave V threshold. Electrocochleograms were obtained with 90 dB nHL 7.1/second alternating clicks and assessed for summating and compound action potentials (APs). Outcomes were compared via independent samples t tests. Linear mixed effects models for behavioral thresholds and ABR wave latencies were constructed to account for potential confounders., Results: Wave I and III latencies were comparable between optimal and non-optimal BP groups. Wave I was prolonged in hypertensive versus optimal BP subjects at stimulus level 70 dB nHL ( p  = 0.016). ABR wave V latencies were prolonged in non-optimal BP at stimulus level 80 dB nHL ( p  = 0.048) and in HTN at levels of 80, 50, and 30 dB nHL (all p  < 0.050). DBP was significantly correlated with wave V latency ( r  = 0.295; p  = 0.039). No differences in ABR amplitudes were observed between optimal and non-optimal BP subjects. Electrocochleographic study showed statistically comparable action and summating potential amplitudes between optimal and non-optimal BP subjects. AP latencies were also similar between the groups. Analysis using a set baseline amplitude of 0 μV showed that hypertensive subjects had higher summating ( p  = 0.038) and AP ( p  = 0.047) amplitudes versus optimal BP subjects; AP latencies were comparable., Conclusion: Elevated BP and more specifically, HTN was associated with subtle AEP abnormalities. This study provides preliminary evidence that nonoptimal BP, and more specifically HTN, may be related to auditory neural dysfunction; larger confirmatory studies are warranted., Competing Interests: None declared., (American Academy of Audiology. This article is published by Thieme.)

Objectives: The association between hearing loss and risk factors for cardiovascular disease, including high blood pressure (BP), has been evaluated in numerous studies. However, data from population- and laboratory-based studies remain inconclusive. Furthermore, most prior work has focused on the effects of BP level on behavioral hearing sensitivity. In this study, we investigated cochlear integrity using distortion product otoacoustic emissions (DPOAEs) in persons with subtle elevation in BP levels (nonoptimal BP) hypothesizing that nonoptimal BP would be associated with poorer cochlear function., Design: Sixty individuals [55% male, mean age = 31.82 (SD = 11.17) years] took part in the study. The authors measured pure-tone audiometric thresholds from 0.25 to 16 kHz and computed four pure-tone averages (PTAs) for the following frequency combinations (in kHz): PTA0.25, 0.5, 0.75, PTA1, 1.5, 2, 3, PTA4, 6, 8, and PTA10, 12.5, 16. DPOAEs at the frequency 2f1-f2 were recorded for L1/L2 = 65/55 dB SPL using an f2/f1 ratio of 1.22. BP was measured, and subjects were categorized as having either optimal BP (systolic/diastolic <120 and <80 mm Hg) or nonoptimal BP (systolic ≥120 or diastolic ≥80 mm Hg or use of antihypertensives). Between-group differences in behavioral thresholds and DPOAE levels were evaluated using 95% confidence intervals. Pearson product-moment correlations were run to assess the relationships between: (1) thresholds (all four PTAs) and BP level and (2) DPOAE [at low (f2 ≤ 2 kHz), mid (f2 > 2 kHz and ≤10 kHz), and high (f2 > 10 kHz) frequency bins] and BP level. Linear mixed-effects models were constructed to account for the effects of BP status, stimulus frequency, age and sex on thresholds, and DPOAE amplitudes., Results: Significant positive correlations between diastolic BP and all four PTAs and systolic BP and PTA0.25, 0.5, 0.75 and PTA4, 6, 8 were observed. There was not a significant effect of BP status on hearing thresholds from 0.5 to 16 kHz after adjustment for age, sex, and frequency. Correlations between diastolic and systolic BP and DPOAE levels were statistically significant at the high frequencies and for the relationship between diastolic BP and DPOAE level at the mid frequencies. Averaged across frequency, the nonoptimal BP group had DPOAE levels 1.50 dB lower (poorer) than the optimal BP group and differences were statistically significant (p = 0.03)., Conclusions: Initial findings suggest significant correlations between diastolic BP and behavioral thresholds and diastolic BP and mid-frequency DPOAE levels. However, adjusted models indicate other factors are more important drivers of impaired auditory function. Contrary to our hypothesis, we found that subtle BP elevation was not associated with poorer hearing sensitivity or cochlear dysfunction. We consider explanations for the null results. Greater elevation in BP (i.e., hypertension itself) may be associated with more pronounced effects on cochlear function, warranting further investigation. This study suggests that OAEs may be a viable tool to characterize the relationship between cardiometabolic risk factors (and in particular, stage 2 hypertension) and hearing health., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose To overcome methodology limitations for studying auditory development in young children, we have recently developed an observer-based procedure that uses a conditioned, play-based, motor response (see Bonino & Leibold, 2017). The purpose of this article was to examine interrater reliability for the method. Method Video recordings of test sessions of 2- to 4-year-old children ( n = 17) were examined. Detection of a 1000-Hz warble tone was measured with the Play Observer-Based, Two-Interval (PlayO2I) method in each of two conditions: for a fixed intensity level (30 dB SPL) or for a variable intensity level signal (0-30 dB SPL). All test sessions were scored independently by three observers (one real-time, two offline). Observer consensus was evaluated with Fleiss' kappa statistic. To determine if summary data were similar across the observers of each test session, the proportion of correct trials (fixed-level condition) or threshold (variable-level condition) were computed. Results The strength of observer consensus was classified as "almost perfect" and "substantial" for the fixed-level and variable-level conditions, respectively. Follow-up analysis of the variable-level data indicated that differences in observer consensus were seen based on the signal level, the type of response behavior provided by the child, and the confidence level of the real-time observer. Resulting summary data were similar across the three observers of each test session: no significant differences for estimates of the proportion of correct trials or threshold. Conclusions Results from this study confirm strong interrater reliability for the method. The PlayO2I method is a powerful tool for measuring detection and discrimination abilities in young children. Supplemental Material https://doi.org/10.23641/asha.12978197.

Purpose Cannabis is widely used for medicinal and recreational purposes. Studies have evaluated its health benefits and consequences, although there is limited work on its effects on the auditory system. In this exploratory study, we evaluate the effects of cannabis smoking on early auditory evoked potentials. Method We investigated auditory brainstem response (ABR) and electrocochleography waveforms in 18 cannabis smokers (44% women, 54% men; M age = 23.06 years, range: 21-28 years) and 19 nonsmoker controls (63% women, 37% men; M age = 23.74 years, range: 21-33 years). Threshold ABRs were recorded using rarefaction clicks at a rate of 17.7/s from 80 dB nHL to Wave V threshold. Resulting amplitudes and latencies for Waves I, III, and V were compared via independent-samples t tests. Electrocochleograms obtained with 90 dB nHL (7.1/s) alternating clicks were assessed for summating and compound action potentials, which were compared between groups using independent-samples t tests. Results ABR Wave I amplitudes were significantly lower in smokers ( M = 0.14 μV, SD = 0.11) compared to nonsmokers ( M = 0.21 μV, SD = 0.10, p = .039) at 80 dB nHL. Wave V latencies were significantly delayed in smokers at 80 dB nHL. Wave I and III latencies did not differ significantly between the two groups. Summating potential/compound action potential ratios were significantly elevated in smokers ( M = 0.30, SD = 0.04) versus nonsmokers ( M = 0.21, SD = 0.05, p = .042). Conclusion We identified significant differences in electrophysiological outcomes between cannabis smokers and nonsmokers. Cannabis smoking may have a subtle neurotoxic effect on the auditory system. Larger confirmatory studies are warranted.

Pair-bond formation depends vitally on neuromodulatory signaling within the nucleus accumbens, but the neuronal dynamics underlying this behavior remain unclear. Using 1-photon in vivo Ca 2+ imaging in monogamous prairie voles, we found that pair bonding does not elicit differences in overall nucleus accumbens Ca 2+ activity. Instead, we identified distinct ensembles of neurons in this region that are recruited during approach to either a partner or a novel vole. The partner-approach neuronal ensemble increased in size following bond formation, and differences in the size of approach ensembles for partner and novel voles predict bond strength. In contrast, neurons comprising departure ensembles do not change over time and are not correlated with bond strength, indicating that ensemble plasticity is specific to partner approach. Furthermore, the neurons comprising partner and novel-approach ensembles are nonoverlapping while departure ensembles are more overlapping than chance, which may reflect another key feature of approach ensembles. We posit that the features of the partner-approach ensemble and its expansion upon bond formation potentially make it a key neuronal substrate associated with bond formation and maturation., Competing Interests: The authors declare no competing interest.

The Karlberg model of human growth describes the infancy, childhood, and puberty (ICP) stages as continuous and overlapping, and defined by transitions driven by sequential additional effects of several endocrine factors that shape the growth trajectory and resultant adult size. Previous research has suggested that a delayed transition from the infancy to the childhood growth stage contributes to sub-optimal growth outcomes. A new method developed to analyze the structure of centile crossing in early life has emerged as a potential tool for identifying the infancy-childhood transition (ICT), through quantifying patterns of adjacent monthly weight-for-age z-score (WAZ) deviation correlations. Using this method, the infancy-childhood transition was identified as taking place at around 12 months of age in two cohorts of UK infants. Here, we apply this method to data collected as part of a longitudinal growth study in rural Gambia [the Hormonal and Epigenetic Regulators of Growth, or HERO-G study, N = 212 (F = 99, M = 113)], in order to identify the ICT and assess whether timing of this transition differs across groups based on sex or birth seasonality. We calculated Pearson correlation coefficients for adjacent monthly WAZ score deviations. Based on the patterns of change in the correlation structure over time, our results suggest that the infancy-childhood transition occurs at around 9 months of age in rural Gambian infants. This points to an accelerated ICT compared to UK infants, rather than a delayed ICT. A comparatively later transition, seen in UK infants, allows maximal extension of the high rates of growth during the infancy stage; an earlier transition as seen in Gambian infants cuts short this period of rapid growth, potentially impacting on growth outcomes in childhood while diverting energy into other processes critical to responses to acute infectious challenges. Growth in later developmental stages in this population offers an extended window for catch-up., (Copyright © 2020 Bernstein, O'Connor, Vance, Affara, Drammeh, Dunger, Faal, Ong, Sosseh, Prentice and Moore.)

Purpose It is challenging to collect reliable behavioral data from toddlers and preschoolers. Consequently, we have significant gaps in our understanding of how auditory development unfolds during this time period. One method that appears to be promising is an observer-based procedure that uses conditioned, play-based responses (Bonino & Leibold, 2017). In order to evaluate the quality of data obtained with this method, this study presented a suprathreshold signal to determine the number of trials 2- to 7-year-old children could complete, as well as the associated hit rate and observer confidence. Method Participants were 23 children (2-7 years old). Children were taught to perform a play-based motor response when they detected the 1000-Hz warble tone signal (at 30 dB SPL). An observer evaluated children's behavior using a 2-interval, 2-alternative testing paradigm. Testing was terminated after 100 trials or earlier, if signs of habituation were observed. Results Data were successfully collected from 22 of the 23 children. Of the 22 children, all but 1 child completed 100 trials. Overall hit rate was high (0.88-1.0; M = 0.94) and improved with listener age. Hit rate was stable across the test session. Strong agreement was seen between the correctness of the response and the observer's confidence in the judgment. Conclusion Results of this study confirm that the 2-interval, observer-based procedure described in this article is a powerful tool for measuring detection and discrimination abilities in young children. Future research will (a) evaluate coder reliability and (b) examine stability of performance across a test session when the signal intensity is manipulated. Supplemental Material https://doi.org/10.23641/asha.8309273.

Pit latrines can provide improved household sanitation, but without effective and inexpensive emptying options, they are often abandoned once full and may pose a public health threat. Emptying techniques can be difficult, as the sludge contents of each pit latrine are different. The design of effective emptying techniques (e.g., pumps) is limited by a lack of data characterizing typical in situ latrine sludge resistance. This investigation aimed to better understand the community education and technical engineering needs necessary to improve pit latrine management. In low income areas within Mzuzu city, Malawi, 300 pit latrines from three distinct areas were assessed using a dynamic cone penetrometer to quantify fecal sludge strength, and household members were surveyed to determine their knowledge of desludging procedures and practices likely to impact fecal sludge characteristics. The results demonstrate that there is a significant difference in sludge strength between lined and unlined pits within a defined area, though sludge hardened with depth, regardless of the pit type or region. There was only limited association between cone penetration depth and household survey data. To promote the adoption of pit emptying, it is recommended that households be provided with information that supports pit emptying, such as latrine construction designs, local pit emptying options, and cost. This study indicates that the use of a penetrometer test in the field prior to pit latrine emptying may facilitate the selection of appropriate pit emptying technology.

Objectives: To examine patient, hospital, and geographic characteristics influencing variation in computed tomography (CT) scan use in inpatients in New York State., Study Design: Retrospective cohort study., Methods: We used the 2007 healthcare cost and utilization project's state inpatient database from the agency for healthcare research and quality and applied descriptive univariate statistics and logistic regression models to quantify the influence of each factor on CT scan use., Results: The primary contributors to variation in CT scan use were the inpatients' diagnosis, age, and hospital county, whereas inpatients' sex and method of payment and hospitals' teaching status and size had very little effect. Inpatients diagnosed with trauma had the highest CT scan use; CT scan use increased with age for inpatients over 30 years; and CT scan use varied widely between counties., Conclusions: After controlling for patient and hospital characteristics, significant geographic variation remained at the level of the county, which indicates that additional research investigating the use of CT scans is necessary to understand the reasons behind small-area variation. Understanding the distribution and practice patterns of specific physician specialties may be helpful in curtailing underuse and overuse.

Pneumocystis carinii pneumonia (PCP) is uncommon in patients undergoing chemotherapy for breast cancer. Most previously described patients with breast cancer and PCP received treatment with corticosteroids, a known risk factor for PCP. We describe two patients with metastatic breast cancer who developed PCP after receiving therapy with high doses of cyclophosphamide with peripheral blood stem cell support. Both patients developed fevers of unclear etiology in the setting of recovery of the neutrophil count. Only one patient had pulmonary symptoms. P. carinii infection was documented in both cases by bronchoscopy. One patient died after prolonged ventilatory support for PCP. Steroid exposure did not appear to be a risk factor for the development of PCP in either patient. Patients receiving sequential high doses of chemotherapy with stem cell support may be at increased risk for PCP. The role of prophylaxis for PCP in this setting should be continually redefined as the type and intensity of chemotherapy, as well as methods of procurement of autologous stem cells, continue to change.

Transmission of hepatitis C virus (HCV) in the setting of allogeneic bone marrow transplantation can occur through an infected marrow donor. Prevention of transmission may reduce the risks of peritransplant complications. We describe a 43-year-old patient with chronic myelogenous leukemia whose HLA-identical donor was found to be HCV antibody positive and HCV RNA positive by polymerase chain reaction (PCR). The patient was HCV antibody negative and HCV RNA negative by PCR of the serum. For 6 months before bone marrow transplantation, the donor was treated with alpha-interferon at a standard dose. After 3 months, HCV RNA was no longer detectable by PCR. Interferon was discontinued 1 week before harvest. Bone marrow cellularity was normal. Engraftment was prompt. The recipient's serum remained negative for HCV RNA at 1, 3, 5, and 10 months after transplantation. Hepatitis C transmission from a viremic donor to an HCV-seronegative recipient may be preventable by treating the donor with alpha-interferon.

Objective: To determine if the addition of recombinant (r) human interleukin (IL)-12 enhances in vitro proliferative responses to Mycobacterium avium of peripheral blood mononuclear cells (PBMC) from HIV-positive donors with CD4 cell counts < 100 x 10(6)/l., Design and Methods: PBMC proliferative responses to virulent and avirulent serovars of M. avium in the presence and absence of exogenously added IL-12 were determined in 24 HIV-positive and 11 HIV-negative donors by 3H-thymidine uptake assay. Changes in CD4 and CD8 cell populations after IL-12 treatment and M. avium stimulation were analyzed by FACS., Results: IL-12 significantly enhanced proliferation of PBMC to both virulent and avirulent M. avium from all 24 HIV-positive donors (P = 0.0001) although the magnitude varied for each donor. In contrast, addition of IL-12 to PBMC from HIV-negative donors only increased the proliferative responses to the virulent M. avium serovar 4 (P = 0.0044). PBMC from HIV-positive donors in the presence of IL-12 responded better to the avirulent serovar of M. avium than the virulent serovar 4. Proliferative responses of HIV-positive donors to M. avium alone, however, were significantly less (P = 0.0013) than that of HIV-negative donors. Increased proliferative responses of HIV-positive donors were independent of CD4 counts. No significant changes in the ratio of CD4+ to CD8+ T cells occurred in either HIV-positive or negative donors under any culture conditions., Conclusion: In vitro proliferative responses of PBMC from HIV-positive donors to M. avium were significantly enhanced by the addition of human rIL-12, which was not dependent on their CD4 cell counts. The use of IL-12 as an enhancer of cell-mediated immunity in AIDS patients against M. avium infections deserves further study.