Correlates of 1-Year Change in Quality of Life in Patients with Urologic Chronic Pelvic Pain Syndrome: Findings from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network.

PURPOSE: We evaluated and identified baseline factors associated with change in health related quality of life among patients with interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS: A total of 191 men and 233 women with interstitial cystitis/bladder pain syndrome or chronic prostatitis/chronic pelvic pain syndrome (collectively referred to as urologic chronic pelvic pain syndrome) were followed for 12 months with bimonthly completion of the Short Form 12 to assess general mental and physical health related quality of life, and with biweekly assessment of condition specific health related quality of life using the Genitourinary Pain Index. A functional clustering algorithm was used to classify participants as improved, stable or worsened for each health related quality of life measure. Ordinal logistic regression was used to determine baseline factors associated with change. RESULTS: Physical health related quality of life improved in 22% of the participants, mental health related quality of life improved in 25% and condition specific health related quality of life improved in 47%. Better baseline physical health related quality of life, older age and the presence of nonurological symptoms were associated with lower likelihood of improvement in physical health related quality of life. Better baseline mental health related quality of life, female sex, and greater baseline depression and stress were associated with a lower likelihood of improvement in mental health related quality of life. Better baseline condition specific health related quality of life and more severe baseline urologic chronic pelvic pain syndrome pain symptoms were associated with a lower likelihood of improvement in condition specific health related quality of life. CONCLUSIONS: While several nonurologic chronic pelvic pain syndrome factors influenced the trajectory of general health related quality of life over time, only condition specific baseline health related quality of life and urologic chronic pelvic pain syndrome symptoms were associated with urologic chronic pelvic pain syndrome specific health related quality of life change. Significant differences in how urologic chronic pelvic pain syndrome impacts various aspects of health related quality of life suggest a multidisciplinary approach to assessment and treatment of these patients.

Author Correction: Developing a molecular picture of soil organic matter-mineral interactions by quantifying organo-mineral binding.

In the original version of this Article, the Acknowledgements section omitted the Department of Energy-funded Environmental and Molecular Sciences Laboratory in which the XRD measurements were performed. This error has now been corrected in both the PDF and HTML versions of the Article.

Developing a molecular picture of soil organic matter-mineral interactions by quantifying organo-mineral binding.

Long residence times of soil organic matter have been attributed to reactive mineral surface sites that sorb organic species and cause inaccessibility due to physical isolation and chemical stabilization at the organic-mineral interface. Instrumentation for probing this interface is limited. As a result, much of the micron- and molecular-scale knowledge about organic-mineral interactions remains largely qualitative. Here we report the use of force spectroscopy to directly measure the binding between organic ligands with known chemical functionalities and soil minerals in aqueous environments. By systematically studying the role of organic functional group chemistry with model minerals, we demonstrate that chemistry of both the organic ligand and mineral contribute to values of binding free energy and that changes in pH and ionic strength produce significant differences in binding energies. These direct measurements of molecular binding provide mechanistic insights into organo-mineral interactions, which could potentially inform land-carbon models that explicitly include mineral-bound C pools.Most molecular scale knowledge on soil organo-mineral interactions remains qualitative due to instrument limitations. Here, the authors use force spectroscopy to directly measure free binding energy between organic ligands and minerals and find that both chemistry and environmental conditions affect binding.

Increased risk of hip fracture associated with dually treated HIV/hepatitis B virus coinfection.

HIV and hepatitis B virus (HBV) infections are each associated with reduced bone mineral density, but it is unclear whether HIV/HBV coinfection is associated with an increased risk of fracture. We determined whether dually treated HIV/HBV patients had a higher incidence of hip fracture compared to treated HBV-monoinfected, antiretroviral therapy (ART)-treated HIV-monoinfected and HIV/HBV-uninfected patients. We conducted a cohort study among 4156 dually treated HIV/HBV-coinfected, 2053 treated HBV-monoinfected, 96,253 ART-treated HIV-monoinfected, and 746,794 randomly sampled uninfected persons within the US Medicaid populations of California, Florida, New York, Ohio and Pennsylvania (1999-2007). Coinfected patients were matched on propensity score to persons in each comparator cohort. Weighted survival models accounting for competing risks were used to estimate cumulative incidences and hazard ratios (HRs) with 95% confidence intervals (CIs) of incident hip fracture for dually treated coinfected patients compared to (i) HBV-monoinfected receiving nucleos(t)ide analogue or interferon alfa therapy, (ii) HIV-monoinfected on ART and (iii) uninfected persons. Dually treated coinfected patients had a higher cumulative incidence of hip fracture compared to ART-treated HIV-monoinfected (at 5 years: 1.70% vs 1.24%; adjusted HR, 1.37 [95% CI, 1.03-1.83]) and uninfected (at 5 years: 1.64% vs 1.22%; adjusted HR, 1.35 [95% CI, 1.03-1.84]) persons. The cumulative incidence of hip fracture was higher among coinfected than treated HBV-monoinfected patients (at 5 years: 0.70% vs 0.27%), but this difference was not statistically significant in competing risk analysis (adjusted HR, 2.62 [95% CI, 0.92-7.51]). Among Medicaid enrollees, the risk of hip fracture was higher among dually treated HIV/HBV-coinfected patients than ART-treated HIV-monoinfected and uninfected persons.

The role of bioactive nanofibers in enamel regeneration mediated through integrin signals acting upon C/EBPα and c-Jun.

Enamel formation involves highly orchestrated intracellular and extracellular events; following development, the tissue is unable to regenerate, making it a challenging target for tissue engineering. We previously demonstrated the ability to trigger enamel differentiation and regeneration in the embryonic mouse incisor using a self-assembling matrix that displayed the integrin-binding epitope RGDS (Arg-Gly-Asp-Ser). To further elucidate the intracellular signaling pathways responsible for this phenomenon, we explore here the coupling response of integrin receptors to the biomaterial and subsequent downstream gene expression profiles. We demonstrate that the artificial matrix activates focal adhesion kinase (FAK) to increase phosphorylation of both c-Jun N-terminal kinase (JNK) and its downstream transcription factor c-Jun (c-Jun). Inhibition of FAK blocked activation of the identified matrix-mediated pathways, while independent inhibition of JNK nearly abolished phosphorylated-c-Jun (p-c-Jun) and attenuated the pathways identified to promote enamel regeneration. Cognate binding sites in the amelogenin promoter were identified to be transcriptionally up-regulated in response to p-c-Jun. Furthermore, the artificial matrix induced gene expression as evidenced by an increased abundance of amelogenin, the main protein expressed during enamel formation, and the CCAAT enhancer binding protein alpha (C/EBPα), which is the known activator of amelogenin expression. Elucidating these cues not only provides guidelines for the design of synthetic regenerative strategies and opportunities to manipulate pathways to regulate enamel regeneration, but can provide insight into the molecular mechanisms involved in tissue formation.

Impact of the human immunodeficiency virus on early multidrug-resistant tuberculosis treatment outcomes in Botswana.

SETTING: The impact of the human immunodeficiency virus (HIV) on multidrug-resistant tuberculosis (MDR-TB) treatment outcomes in sub-Saharan Africa, where extensive rollout of highly active antiretroviral therapy (HAART) has occurred, remains unclear. OBJECTIVE: To compare the time to initial culture conversion among patients with and those without HIV infection in a setting of individualized MDR-TB care in Botswana. DESIGN: Prospective cohort study of MDR-TB patients receiving ambulatory, integrated TB-HIV care at two public clinics in Botswana. The time to culture conversion was compared by HIV status using Cox proportional hazard ratios (HRs). RESULTS: A total of 40 HIV-infected and 30 non-HIV-infected patients with MDR-TB and follow-up cultures were identified. The median time to initial culture conversion was 78 days (interquartile range [IQR] 42-186) for HIV-infected and 95 days (IQR 70-133) for non-HIV-infected individuals (log rank P > 0.5; unadjusted HR 0.9, 95%CI 0.5-1.5). Adjusting for age, sex, treatment history and number of active anti-tuberculosis drugs did not change this result (adjusted HR 0.8, 95%CI 0.4-1.4). CONCLUSION: We found no difference in the proportion of or time to initial sputum culture conversion between an HIV-infected and a non-infected cohort of MDR-TB patients in Botswana, suggesting that outcomes may be comparable in similar settings with access to individualized anti-tuberculosis treatment and HAART.

Dosing algorithms to predict warfarin maintenance dose in Caucasians and African Americans.

The objective of this study was to determine whether warfarin dosing algorithms developed for Caucasians and African Americans on the basis of clinical, environmental, and genetic factors will perform better than an empirical starting dose of 5 mg/day. From April 2002 through December 2005, 259 subjects (Caucasians and African Americans) who started using warfarin were prospectively followed until they reached maintenance dose. The Caucasian algorithm included 11 variables (R(2) = 0.43). This model (which predicted 51% of the doses to within 1 mg of the observed dose) performed better than 5 mg/day (which predicted 29% of the doses to within 5 +/- 1 mg). The African-American algorithm included 10 variables (R(2) = 0.28). This model predicted 37% of the doses to within 1 mg of the observed dose, representing a small improvement compared with 5 mg/day (which predicted 34% of the doses to within 1 mg of 5 mg/day). These results were similar to the results we obtained from testing other published algorithms. The dosing algorithms explained <45% of the observed variability in Caucasians, and the algorithms performed only marginally better for African Americans when compared with giving 5 mg empirically.

Apolipoprotein E genotype and warfarin dosing among Caucasians and African Americans.

Warfarin sodium is a vitamin K antagonist that is plagued by large variability in patient response, including higher dose requirements among African Americans. Polymorphisms in the gene encoding apolipoprotein E (APOE) may partly explain this variability by altering transport of vitamin K to the liver. In a prospective cohort study of 232 individuals (52.2% Caucasian and 47.8% African American) initiating warfarin therapy, the weekly maintenance dose was significantly higher for African Americans than for Caucasians (mean 42.9 versus mean 36.9 mg, P=0.018), and the epsilon4 allele was more common among African Americans (37.8 versus 26.4% for Caucasians). In multivariable analyses, the presence of the epsilon4 allele was associated with a statistically significantly higher warfarin dose among African Americans (median 45.0 mg in epsilon4 carriers versus 35.0 mg in non-epsilon4 carriers, P=0.014) but not Caucasians (38.1 versus 35.0 mg, P=0.60). In addition, warfarin maintenance dose increased among African Americans according to genotype previously associated with differential hepatic chylomicron clearance (epsilon2/epsilon2 or epsilon2/epsilon3: 30.0 mg; epsilon3/epsilon3: 35.0 mg; epsilon3/epsilon4 or epsilon4/epsilon4: 45.0 mg; P=0.012), although the epsilon4/epsilon4 genotype was rare and not clearly associated with higher doses. The association of APOE with warfarin dosing was independent of CYP2C9 and VKORC1 polymorphisms. APOE polymorphisms thus may be important determinants of warfarin maintenance dose and could explain at least some of the observed racial differences in dose requirements.

Warfarin response and vitamin K epoxide reductase complex 1 in African Americans and Caucasians.

The objective of this study was to determine whether two vitamin K epoxide reductase complex 1 (VKORC1) polymorphisms contribute to the variability in warfarin response, particularly in African Americans. The effect of the VKORC1 1173C/T and -1639G/A polymorphisms was examined in a prospective cohort study of 338 warfarin users. Subjects carrying an 1173T allele had a lower warfarin maintenance dose compared with subjects with the CC genotype in African Americans (-12.10 mg/week+/-4.93; P=0.02) and Caucasians (-14.41 mg/week+/-3.28; P<0.001). Before reaching maintenance dose, only Caucasians with the T allele had significantly increased risk of international normalized ratio >3 (odds ratio=3.10; 95% confidence interval: 1.73-5.55) compared with Caucasians with the CC genotype. Polymorphisms in the VKORC1 gene are associated with warfarin maintenance dose requirements among both African Americans and Caucasians. However, these polymorphisms may not be as useful in predicting over-anticoagulation among African Americans.

Modeling SSI financial eligibility and simulating the effect of policy options.

This article simulates eligibility for Supplemental Security Income (SSI) among the elderly, analyzes factors affecting participation, and looks at the potential effects of various options to modify financial eligibility standards for the federal SSI program. We find that in the estimated noninstitutional elderly population of 30.2 million in the United States in 1991, approximately 2 million individuals aged 65 or older were eligible for SSI (a 6.6 percent rate of eligibility). Our overall estimate of the rate of participation among eligible elderly is approximately 63 percent, suggesting that more than a third of those who are eligible do not participate in the program. The results of our analysis of factors affecting participation among the eligible elderly show that expected SSI benefits and a number of demographic and socioeconomic variables are associated with the probability of participation. We also simulate the effects of various policy options on the poverty rate, poverty gap, annual program cost, the number of participants, and the average estimated benefits among participants. The simulations consider the potential effects of five policy alternatives: Increase the general income exclusion (GIE) from $20 to $80. Increase the earned income exclusion (EIE) from $65 to $260. Increase the federal benefit rate (FBR) by $50 for individuals and $75 for couples and eliminate the GIE. Increase the asset threshold to $3,000 for individuals and $4,500 for couples. Increase the asset threshold to $6,000 for individuals and $9,000 for couples. Using 1991 microdata from the Survey of Income and Program Participation (SIPP) matched to Social Security Administration administrative records and making adjustments reflecting aggregate program statistics, we present the results of our simulations for December 1999. The results show substantial variation in the simulated effects of the five policy alternatives along the various outcome dimensions considered. The simulated effects on the poverty gap of the elderly population range from a 7.9 percent reduction ("Increase the GIE from $20 to $80") to a 0.1 percent reduction ("Increase the EIE from $65 to $260"). All simulated interventions are expected to increase the rate of SSI participation among the elderly from a high of 20.3 percent ("Increase the GIE from $20 to $80") to a low of 0.5 percent ("Increase the EIE from $65 to $260"). We also find that the interventions that have greater estimated effects in terms of increased participation and reduced poverty tend to cost more. At the high end, we estimate that increasing the GIE from $20 to $80 could raise annual federal SSI cash benefit outlays by about 46 percent, compared with only 0.9 percent for increasing the EIE from $65 to $260. Similar to the EIE intervention, raising the resource thresholds by 50 percent would reduce the overall poverty gap of the elderly by only 0.2 percent, would increase SSI participation only modestly (by 1.3 percent), but would entail slightly higher program costs (by 1.4 percent). Increasing the asset threshold by 200 percent would have higher estimated effects on all three outcomes, but it would still be associated with relatively low increases in both costs and benefits. Finally, the simulated effects on the three key outcomes of increasing the FBR by $50 for individuals and $75 for couples, combined with eliminating the GIE, are relatively large but are clearly less substantial than increasing the GIE from $20 to $80. This work relies on data from the SIPP matched to administrative data on federal SSI benefits that provide a more accurate picture of SSI participation than has been feasible for previous studies. We simulate eligibility for federal SSI benefits by applying the program rules to detailed information on the characteristics of individuals and couples based on the rich array of demographic and socioeconomic data in the SIPP, particularly the comprehensive information SIPP provides on assets and monthly income. A probit model is estimated to analyze factors affecting participation among the eligible elderly. Finally, we conduct the policy simulations using altered program rules represented by the policy alternatives and predicted participation probabilities to estimate outcomes under simulated program rules. We compare those simulated outcomes to observed outcomes under current program rules. The results of our simulations are conditional on the characteristics of participants and eligibles in 1991, but they also reflect aggregate adjustments capturing substantial changes in overall participation and program benefit levels between 1991 and 1999.

Definition and adjustment of Cesarean section rates and assessments of hospital performance.

BACKGROUND: Demand is growing for comparative data such as Cesarean section rates, but little effort has been made to develop either standardized definitions or risk adjustment approaches. OBJECTIVE: To determine to what extent a seemingly straightforward indicator like Cesarean section rate will vary when calculated according to differing definitions used by various performance measurement systems. DESIGN: Retrospective data abstraction of 200 deliveries per hospital. SETTING: Fifteen acute care hospitals including two from outside the USA. MEASUREMENTS: Four widely-used performance measurement systems provided specifications for their Cesarean section indicators. Indicator specifications varied on inclusion criteria (whether the population was defined using Diagnostic Related Groups or ICD-9-CM procedure codes or ICD-9-CM diagnosis codes) and risk-adjustment methods and factors. Rates and rankings were compared across hospitals using different Cesarean section indicator definitions and indicators with and without risk adjustment. RESULTS: Calculated Cesarean section rates changed substantially depending on how the numerator and denominator cases were identified. Relative performance based on Cesarean section rankings is affected less by differing indicator definitions than by whether and how risk adjustment is performed. CONCLUSIONS: Judgments about organizational performance should only be made when the comparisons are based upon identical indicators. Research leading to a uniform indicator definition and standard risk adjustment methodology is needed.

The proapoptotic function of Drosophila Hid is conserved in mammalian cells.

Three genes-reaper, grim, and hid-are crucial to the regulation of programmed cell death in Drosophila melanogaster. Mutations involving all three genes virtually abolish apoptosis during development, and homozygous hid mutants die as embryos with extensive defects in apoptosis. Although Hid is central to apoptosis in Drosophila, it has no mammalian homologue identified to date. We present evidence that expression of Drosophila Hid in mammalian cells induces apoptosis. This activity is subject to regulation by inhibitors of mammalian cell death. We show that the N terminus of Hid, which is a region of homology with Reaper and Grim, is essential for Hid's function in mammalian cells. We demonstrate that Hid is localized to the mitochondria via a hydrophobic region at its C terminus and functionally interacts with BclXL. This study shows that the function of Hid as a death inducer in Drosophila is conserved in mammalian cells and argues for the existence of a mammalian homologue of this critical regulator of apoptosis.

Measuring the effects of reminders for outpatient influenza immunizations at the point of clinical opportunity.

OBJECTIVE: To evaluate the influence of computer-based reminders about influenza vaccination on the behavior of individual clinicians at each clinical opportunity. DESIGN: The authors conducted a prospective study of clinicians' influenza vaccination behavior over four years. Approximately one half of the clinicians in an internal medicine clinic used a computer-based patient record system (CPR users) that generated computer-based reminders. The other clinicians used traditional paper records (PR users). MEASUREMENTS: Each nonacute visit by a patient eligible for an influenza vaccination was considered an opportunity for intervention. Patients who had contraindications for vaccination were excluded. Compliance with the guideline was defined as documentation that a clinician ordered the vaccine, counseled the patient about the vaccine, offered the vaccine to a patient who declined it, or verified that the patient had received the vaccine elsewhere. The authors calculated the proportion of opportunities on which each clinician documented action in the CPR and PR user groups. RESULTS: The CPR and PR user groups had different baseline compliance rates (40.1 and 27.9 per cent, respectively; P<0.05). Both rates remained stable during a two-year baseline period (P = 0.34 and P = 0.47, respectively). The compliance rates in the CPR user group increased 78 per cent from baseline (P<0.001), whereas the rates for the PR user group did not change significantly (P = 0.18). CONCLUSIONS: Clinicians who used a CPR with reminders had higher rates of documentation of compliance with influenza-vaccination guidelines than did those who used a paper record. Measurements of individual clinician behavior at the point of each clinical opportunity can provide precise evaluation of interventions that are designed to improve compliance with guidelines.

Informing patients: a guide for providing patient health information.

OBJECTIVE: To understand and address patients' need for information surrounding ambulatory-care visits. DESIGN: The authors conducted two patient focus groups regarding patient education. The first covered general information needs of patients and the second explored their reactions to a computer-generated patient handout that was developed in response to the results of the first focus group and implemented in a clinic. RESULTS: Participants sought information about their health--generally after the encounter with their caregiver. They wanted a permanent record of personal health data and relevant educational information. Participants recommended that the information be concise, clear, and illustrated with graphics if appropriate. Receiving health-related information from their providers favorably affected the participants' trust in, relationship with, and confidence in their physicians. When given printouts with graphic trends depicting their responses to therapy, participants reported that they were more motivated to adhere to a treatment plan and were more satisfied with their care. Based on the results of the focus groups, we developed a set of attributes (P.A.T.I.E.N.T.) to guide the development of patient and consumer health information. CONCLUSIONS: Patients participating in our focus groups felt that providing printed summary information to patients at the end of a clinic visit improves their understanding of their care, enhances their relationships with providers, improves their satisfaction with care, and motivates them to adhere to treatment plans. Further empirical studies are necessary to test their perceptions.

Meeting the information needs of patients: results from a patient focus group.

Changing roles in health care call for patients to share increased responsibility for managing their health. Patients may need additional health-related information to participate more fully in health care decisions. We examined patients' information needs from the perspective of clinicians, educational software vendors, and patients. The most instructive information came directly from patients in focus groups. The participants in our focus groups clearly sought more information about their health than they had received during visits with their physicians. Patients' needs were specific to their individual clinical situation, and timing was critical. Although physicians spend a significant amount of time on patient education during an encounter, patients typically formulate their questions after the encounter. We used the results of focus groups to develop desired characteristics of patient education material that addresses patients' information needs. Providers who understand and address these needs will be in a better position to effectively engage patients' active participation in their health care.

Trimeric interactions of the invariant chain and its association with major histocompatibility complex class II alpha beta dimers.

The invariant chain (I chain) associates with major histocompatibility complex class II alphabeta heterodimers upon synthesis, preventing them from binding peptides and unfolded proteins in the endoplasmic reticulum and directing class II transport to post-Golgi endosomal compartments. To assess which regions of the I chain are involved in binding class II molecules, we have studied proteolytic fragments of the I chain generated both by natural proteolytic degradation of alphabeta dimer-invariant chain complexes (alphabeta.I) within human B cells and by in vitro digestion of purified alphabeta middle dotI complexes with proteinase K. The 18-kDa luminal I chain fragment generated by proteinase K, called K3, remains associated with alphabeta dimers and retains the complex (alphabeta.K3) in a high molecular mass nonameric configuration. The N terminus of the K3 fragment was identified as glycine 110. This indicates that the K3 fragment lies outside of the class II-associated invariant chain peptide region (amino acids 81-104) of the I chain, shown to be important for initial alphabeta.I assembly. An N-terminal 12-kDa I chain fragment called p12, generated intracellularly, was also analyzed and was found to remain associated with alphabeta dimers in a high molecular mass form analogous to the nonameric alphabeta.I complex. These results demonstrate that at least two class II contact points exist along the length of the I chain and that different regions of the I chain can stabilize the alphabeta.I nonamer. Additional evidence suggests that the O-linked glycan(s) characteristic of the I chain is added to the short C-terminal region absent from the K3 fragment.

Assembly and intracellular transport of HLA-DM and correction of the class II antigen-processing defect in T2 cells.

MHC class II molecules expressed in T2 cells fail to acquire a normal complement of endocytically generated peptides. The defect is repaired by introducing HLA-DMA and HLA-DMB cDNA expression vectors, determined by the restoration of SDS stability of class II alpha beta dimers, restoration of a normal conformation for HLA-DR3 as detected by a monoclonal antibody, and by a reduction in class II-associated invariant chain peptides. The intracellular distribution of class II and invariant chain molecules is also restored to that of wild-type cells. The HLA-DMA and HLA-DMB products appear to form a heterodimer that, although transported at least to the medial Golgi, is not expressed at the cell surface. These findings are consistent with HLA-DM functioning intracellularly to facilitate class II-restricted antigen processing.

The role of magnetic resonance for assessing radiation-induced lung damage.

PURPOSE: To investigate the potential role of Magnetic Resonance for assessing radiation-Induced lung damage. METHODS AND MATERIALS: T1 and T2 relaxation times were measured for lungs excised from Sprague-Dawley rats at various times following thoracic irradiation. RESULTS: Although on average a 10% increase was observed in the T2 relaxation times between 30 and 80 days after irradiation, this is too small to affect image contrast. CONCLUSIONS: The results indicate that relaxation measurements are unlikely to yield new information to characterize changes in lung tissue caused by radiation.

Radiation-induced lung damage in rats: the influence of fraction spacing on effect per fraction.

PURPOSE: When the linear-quadratic model is used to predict fractionated treatments which are isoeffective, it is usually assumed that each (equal size) treatment fraction has an equal effect, independent of the time at which it was delivered during a course of treatment. Previous work by our group has indicated that this assumption may not be valid in the context of radiation-induced lung damage in rats. Consequently we tested directly the validity of the assumption that each fraction has an equal effect, independent of the time it is delivered. METHODS AND MATERIALS: An experiment was completed in which fractionated irradiation was given to whole thoraces of Sprague-Dawley rats. All treatment schedules consisted of eleven equal dose fractions in 36 days given as a split course, with some groups receiving the bulk of the doses early in the treatment schedule, before a 27-day gap, and others receiving most of the dose toward the end of the treatment schedule, after the time gap. To monitor the incidence of radiation-induced damage, breathing rate and lethality assays were used. RESULTS: The maximum differences in the LD50s and breathing rate ED50s for the different fractionation schedules were 4.0% and 7.7% respectively. The lethality data and breathing rate data were consistent with results expected from modelling using the linear-quadratic model with the inclusion of an overall time factor, but not the generalized linear-quadratic model which accounted for fraction spacing. CONCLUSION: For conventional daily fractionation, and within the range of experimental uncertainties, the results indicate that the effect of a treatment fraction does not depend on the time at which it is given (its position) in the treatment. The results indicate no need to extend isoeffect formulae to consider the effect of each fraction separately for radiation-induced lung damage.

Ultrasonic measurements of breathing rate in rats and computer assisted analysis.

PURPOSE: An ultrasound breathing rate measurement technique and a computer analysis algorithm have been developed to reduce the amount of time needed to collect and analyze animal breathing rate data, as well as to improve the testing environment. The system is not airtight, therefore, acclimatization and collection time is not limited, and the technique makes use of a top loading apparatus to facilitate animal entry. METHODS AND MATERIALS: Breathing rate is measured using two ultrasound transducers housed directly above the rat thorax in the plexiglass jig. The breathing rate signal is stored and evaluated by computer. The ultrasound technique was tested using a loud speaker driven by a signal generator, over a range of 30 to 450 cycles/min. In addition, the ultrasonic breathing rate method was used to record the breathing rate response of Sprague Dawley rats, treated with graded single doses of radiation, over a period of 170 days. RESULTS: For the loud speaker tests, the measured frequency agreed with that of the input signal with a maximum deviation of 1%. For the animal irradiations, all breathing rate data were analyzed by both user and computer selection of regular breathing. The techniques gave the same results at the 95% confidence limit. Using the computer program to assess the traces, 240 breathing rates can be determined per hour, from previously measured data. CONCLUSION: A new technique for measuring breathing rate has been developed and enhances both the collection and analysis of data.