Depression and Engagement in Care Among Newly Diagnosed HIV-Infected Adults in Johannesburg, South Africa.

Delayed engagement in HIV care threatens the success of HIV treatment programs in sub-Saharan Africa and may be influenced by depression. We examined the relationship between depression prior to HIV diagnosis and engagement in HIV care at a primary care clinic in Johannesburg, South Africa. We screened 1683 patients for depression prior to HIV testing using the Patient Health Questionnaire-9. Among patients who tested positive for HIV we assessed linkage to HIV care, defined as obtaining a CD4 count within 3 months. Among those who linked to care and were eligible for ART, we assessed ART initiation within 3 months. Multivariable Poisson regression with a robust variance estimator was used to assess the association between depression and linkage to care or ART initiation. The prevalence of HIV was 26 % (n = 340). Among HIV-infected participants, the prevalence of depression was 30 %. The proportion of linkage to care was 80 % among depressed patients and 73 % among patients who were not depressed (risk ratio 1.08; 95 % confidence interval 0.96, 1.23). Of the participants who linked to care, 81 % initiated ART within 3 months in both depressed and not depressed groups (risk ratio 0.99; 95 % confidence interval 0.86, 1.15). Depression was not associated with engagement in HIV care in this South African primary care setting. Our unexpected findings suggest that some depressed HIV-infected patients might be more likely to engage in care than their counterparts without depression, and highlight the complex relationship between depression and HIV infection. These findings have led us to propose a new framework relating HIV infection, depression, and the population under study.

Structure of the C-terminal domain of the prokaryotic sodium channel orthologue NsvBa.

Crystallographic and electrophysiological studies have recently provided insight into the structure, function, and drug binding of prokaryotic sodium channels. These channels exhibit significant sequence identities, especially in their transmembrane regions, with human voltage-gated sodium channels. However, rather than being single polypeptides with four homologous domains, they are tetramers of single domain polypeptides, with a C-terminal domain (CTD) composed of an inter-subunit four helix coiled coil. The structures of the CTDs differ between orthologues. In NavBh and NavMs, the C-termini form a disordered region adjacent to the final transmembrane helix, followed by a coiled-coil region, as demonstrated by synchrotron radiation circular dichroism (SRCD) and double electron-electron resonance electron paramagnetic resonance spectroscopic measurements. In contrast, in the crystal structure of the NavAe orthologue, the entire C-terminus is comprised of a helical region followed by a coiled coil. In this study, we have examined the CTD of the NsvBa from Bacillus alcalophilus, which unlike other orthologues is predicted by different methods to have different types of structures: either a disordered region adjacent to the transmembrane region, followed by a helical coiled coil, or a fully helical CTD. To discriminate between the two possible structures, we have used SRCD spectroscopy to experimentally determine the secondary structure of the C-terminus of this orthologue and used the results as the basis for modeling the open and closed conformations of the channel.

Validity of the Patient Health Questionnaire-9 to screen for depression in a high-HIV burden primary healthcare clinic in Johannesburg, South Africa.

BACKGROUND: Integration of depression screening into primary care may increase access to mental health services in sub-Saharan Africa, but this approach requires validated screening instruments. We sought to validate the Patient Health Questionnaire-9 (PHQ-9) as a depression screening tool at a high HIV-burden primary care clinic in Johannesburg, South Africa. METHODS: We conducted a validation study of an interviewer-administered PHQ-9 among 397 patients. Sensitivity and specificity of the PHQ-9 were calculated with the Mini International Neuropsychiatric Interview (MINI) as the reference standard; receiver operating characteristic (ROC) curve analyses were performed. RESULTS: The prevalence of depression was 11.8%. One-third of participants tested positive for HIV. HIV-infected patients were more likely to be depressed (15%) than uninfected patients (9%; p=0.08). Using the standard cutoff score of ≥10, the PHQ-9 had a sensitivity of 78.7% (95% CI: 64.3-89.3) and specificity of 83.4% (95% CI: 79.1-87.2). The area under the ROC curve was 0.88 (95% CI: 0.83-0.92). Test performance did not vary by HIV status or language. In sensitivity analyses, reference test bias associated with the MINI appeared unlikely. LIMITATIONS: We were unable to conduct qualitative work to adapt the PHQ-9 to this cultural context. CONCLUSION: This is the first validation study of the PHQ-9 in a primary care clinic in sub-Saharan Africa. It highlights the potential for using primary care as an access point for identifying depressive symptoms during routine HIV testing. The PHQ-9 showed reasonable accuracy in classifying cases of depression, was easily implemented by lay health workers, and is a useful screening tool in this setting.

Medication use is associated with fatigue in a sample of community-living individuals who have a spinal cord injury: a chart review.

OBJECTIVES: To investigate the relationship between medications known to cause fatigue in spinal cord injury (SCI) and fatigue severity and to describe the pattern of prescription of these medications. STUDY DESIGN: Retrospective chart review. SETTING: GF Strong Rehabilitation Centre, Vancouver, British Columbia, Canada. METHODS: Medical charts of 136 individuals admitted to the GF Strong Outpatient SCI Program between December 2004 and May 2007 were reviewed. Data collected included information on medications, clinical and demographic characteristics and Fatigue Severity Scale (FSS) scores. Multiple linear regression techniques were used to analyse the data. RESULTS: Fifty-two percent of the subjects had clinically relevant fatigue. As a group, the subjects were taking 147 different medications; 41/147 medications were identified as causing fatigue. The two most commonly prescribed categories of medications were antispasticity medications (75 subjects) and analgesic medications (61 subjects). Although several variables were found to contribute to the FSS scores including the use of fatigue-causing medications, the presence of pain (7.6% of variance) and the use of fatigue-causing analgesics (4.2% of variance) explained the most variance in the scores. CONCLUSION: Fatigue is prevalent in outpatients with SCI. Fatigue-causing medications contribute to a higher FSS score. Clinicians treating persons with SCI should be aware that fatigue is a common and significant problem. Clinicians should be aware that fatigue may be exacerbated by the use of medication and should enquire about the effects of medication on fatigue when assessing and prescribing new medications.

Clinical correlates of fatigue in spinal cord injury.

STUDY DESIGN: Retrospective chart review. OBJECTIVES: To determine the prevalence of fatigue in an outpatient spinal cord injury population and to examine the clinical variables contributing to that fatigue. SETTING: GF Strong Rehabilitation Centre, Vancouver, British Columbia, Canada. METHODS: Medical charts of 76 individuals admitted to the GF Strong Outpatient SCI Program between December 2004 and December 2005 were reviewed. Data collected included information on clinical characteristics, demographics and Fatigue Severity Scale (FSS) scores. Multivariable analysis was completed to determine the independent association between these variables and fatigue severity. RESULTS: A total of 57% (95% confidence interval (CI)=45-67%) of the sample were found to have fatigue severe enough to interfere with function. People that were admitted for medical reasons; had pain, spasticity, incomplete injuries, and/or were on more that one medication with a known side effect of fatigue had significantly higher FSS scores. Multivariable analysis indicated incomplete injury was the only statistically significant predictor of a higher FSS scores; pain approached significance (P=0.07, CI=-0.09, 2.06). Together these variables account for 18% of the variance in FSS scores in this sample. CONCLUSION: Fatigue among individuals with spinal cord injury who are seeking outpatient rehabilitation is very common. The severity of fatigue was greater for individuals with incomplete lesions. Pain was also a potentially important covariate of fatigue. Further research is required to determine what else contributes to fatigue severity beyond these clinical variables as only minimal variance was accounted for in our model.

Tuberculin reactivity in bacille Calmette-Guérin vaccinated populations: a compilation of international data.

SETTING: The effect of previously administered bacille Calmette-Guérin (BCG) vaccine on subsequent tuberculin skin tests (TSTs) complicates screening for latent tuberculosis infection (LTBI) in foreign-born persons. OBJECTIVE: To determine the usefulness of the TST as a screening test for LTBI in foreign-born persons. DESIGN: A literature search was performed of published studies that compared tuberculin reactivity amongst BCG-vaccinated and non-vaccinated groups. The percentages of positive reactors in the two groups were then used to calculate a prevalence ratio. RESULTS: The prevalence ratio varied with the age of the groups tested and the incidence of TB in their countries of origin. The TST performed poorly in vaccinated persons of all ages from countries of low TB incidence, but was a useful screen for LTBI in vaccinated adults from countries of high and intermediate incidence. The test performed poorly as a screening method for vaccinated children under 2 years of age. Its usefulness in vaccinated children aged 2-14 years varied considerably. CONCLUSIONS: The usefulness of the TST as a screening method for LTBI depends on the age of the patient and the incidence of TB in their country of origin.

LCR testing for gonorrhoea and chlamydia in population surveys and other screenings of low prevalence populations: coping with decreased positive predictive value.

OBJECTIVE: Nucleic acid amplification tests have facilitated field based STD studies and increased screening activities. However, even with highly specific tests, the positive predictive value (PPV) of such tests may be lower than desirable in low prevalence populations. We estimated PPVs for a single LCR test in a population survey in which positive specimens were retested. METHODS: The Baltimore STD and Behavior Survey (BSBS) was a population based behavioural survey of adults which included collecting urine specimens to assess the prevalence of gonorrhoea and chlamydial infection. Gonorrhoea and chlamydial infection were diagnosed by ligase chain reaction (LCR). Nearly all positive results were retested by LCR. Because of cost considerations, negative results were not confirmed. Predicted curves for the PPV were calculated for a single testing assuming an LCR test sensitivity of 95%, and test specificities in the range 95.0%-99.9%, for disease prevalences between 1% and 10%. Positive specimens were retested to derive empirical estimates of the PPV of a positive result on a single LCR test. RESULTS: 579 participants age 18-35 provided urine specimens. 20 (3.5%) subjects initially tested positive for chlamydial infection, and 39 (6.7%) tested positive for gonococcal infection. If positive results on the repeat LCR are taken as confirmation of a "true" infection, the observed PPV for the first LCR testing was 89.5% for chlamydial infection and 83.3% for gonorrhoea. This is within the range of theoretical PPVs calculated from the assumed sensitivities and specificities of the LCR assays. CONCLUSIONS: Empirical performance of a single LCR testing approximated the theoretically predicted PPV in this field study. This result demonstrates the need to take account of the lower PPVs obtained when such tests are used in field studies or clinical screening of low prevalence populations. Repeat testing of specimens, preferably with a different assay (for example, polymerase chain reaction), and disclosure of the non-trivial potential for false positive test results would seem appropriate in all such studies.

Rational testing of the HIV-exposed infant.

OBJECTIVES: The objectives of this study were 1) to evaluate testing regimens of human immunodeficiency virus (HIV)-exposed infants and 2) to determine optimal methods of follow-up by enzyme-linked immunosorbent assay (ELISA) testing. METHODS: We reviewed the results from 742 HIV-exposed infants in the state of North Carolina; 2474 samples were tested for HIV by DNA polymerase chain reaction (PCR) at the University of North Carolina Retrovirology Core Laboratory. We then reviewed the utility and costs of ELISA testing of all HIV-exposed infants who were seen at the Duke University Pediatric Infectious Disease Clinic between January 1, 1993, and May 5, 1998. We used likelihood ratios to model probability of HIV infection given 3 negative DNA (PCR) tests and to provide recommendations on the use of ELISA follow-up. RESULTS: The overall sensitivity of the DNA PCR was 87.1%, and its specificity was 99.9%. We evaluated 224 HIV-exposed infants who were seen at Duke University and who had at least 3 negative diagnostic tests using either DNA PCR tests or HIV blood cultures. All 178 infants who subsequently underwent ELISA testing ultimately demonstrated seroreversion. The Duke University Pediatric Infectious Disease Clinic transferred the care of 65 patients to primary care physicians before ELISA testing and retained the care of the remaining 159 patients. Children who remained in Duke's care were more likely to have documentation of seroreversion (158 of 159 vs 20 of 65). We reviewed costs of travel, physician appointment, and HIV antibody testing in a tertiary care setting. Given 3 negative PCR tests, the expected cost per case of HIV detected by a positive ELISA assay is $23.8 million. CONCLUSIONS: Documentation of seroreversion in this cohort was nearly complete in the multidisciplinary subspecialty clinic but not when such responsibility was left to the primary care physician. Given the low probability of disease in patients who have had 3 negative PCR tests, documentation of a negative ELISA may not be an appropriate use of medical resources.

Selective screening for cervical neoplasia: an approach for resource-poor settings.

BACKGROUND: Cervical malignancies are the leading cause of cancer-related morbidity and mortality among women in developing countries. Although early detection programmes using cytological methods, followed by aggressive treatment of precursor lesions are accepted as the main disease control strategy, fiscal limitations make this strategy unfeasible in many countries. METHODS: To screen selectively, we developed two risk scores using data from a population-based case-control study in Jamaica with 202 cases and 363 controls. Independent risk factors for cervical neoplasia were determined using logistic regression. An unweighted risk score for each subject was developed by a simple count of risk factors present and a weighted risk score was calculated by summing regression coefficients for each risk factor. RESULTS: Four patient characteristics were independently predictive of cervical neoplasia, older age (OR = 3.4, 95% CI : 1.8-6.7), > or = 4 pregnancies (OR = 5.6, 95% CI : 1.2-18.7), poverty (OR = 2.1, 95% CI : 1.3-3.3) and cigarette smoking (OR = 1.9, 95% CI : 1.2-3.2). Using cut-off points of > or = 20 for the weighted scores and > 3 for unweighted scores, the sensitivity and specificity were 65% and 69% for the unweighted score and 75% and 61%, respectively, for the weighted score. Areas under the receiver operating characteristic (ROC) curves for the weighted versus the unweighted scores were similar, suggesting similar overall accuracy. CONCLUSION: Selective screening using risk assessment strategies is potentially useful, particularly in resource-poor settings. However, whether weighting factors is essential is dependent on prevalence of factors in a given setting. Although this approach needs validation in other populations, women at highest risk for cervical neoplasia can be identified using demographic factors available during a regular clinic visit.

Selective screening for chlamydial infection: which criteria to use?

BACKGROUND: Screening sexually active women for Chlamydia trachomatis is necessary to detect asymptomatic infections. Selective screening is a common strategy because universal screening is too costly in many settings. In order to guide local programs in the choice of selective screening criteria, we examined the performance of previously proposed screening criteria for C. trachomatis. METHODS: A clinic-based, cross-sectional study was conducted in public family planning and sexually transmitted disease (STD) clinics in ten counties in North Carolina. Women (n = 4471 in family planning and n = 2201 in STD clinics) undergoing pelvic examination were enrolled consecutively. Nine sets of screening criteria, including age alone, were compared using sensitivity, specificity, number of tests required and receiver-operator characteristic (ROC) analysis. All women underwent testing with ligase chain reaction assay of cervical specimens to identify C trachomatis infection. RESULTS: The prevalence of C. trachomatis was 7.8% and 11.0% in family planning and STD clinics, respectively. The sensitivities of published criteria ranged from 0.50 to 0.97. Specificities ranged from 0.05 to 0.66. In family planning clinics, the best performing criteria would detect 84% of infections while screening 51% of women. In STD clinics, the same criteria would detect 83% of infections but require testing 67% of women. Testing women aged < or =22 would detect 77% of infections in family planning and 74% of infections in STD clinics, while testing 51% and 48% of the women, respectively. CONCLUSIONS: When site-specific criteria cannot be developed, age alone is an acceptable strategy for selective screening for chlamydial infection.

Reassessing the role of epidemiology in public health.

This commentary examines the scope of epidemiology and delineates the role of epidemiology in relation to public health. Epidemiology is a science; public health is a mission that is implemented through societal action. The implications of this difference are considered, and the sufficiency of epidemiology for guiding public health is evaluated in relation to other scientific disciplines and nonscientific considerations. The authors conclude that epidemiology is not the basic science of public health but one of many contributors to guiding action. The need for public health decisions despite scientific uncertainty and the potential for epidemiologic certainty's failing to provide clear guidance to public health action emphasize the distinctiveness of these endeavors. Criticisms that epidemiology fails to solve major public health problems, such as tobacco use; that it overemphasizes methods; that it fails to meet the needs of public health practitioners; and that it isolates itself from public health ethics are unwarranted. However, epidemiology should focus on addressing issues that directly affect public health decisions and should clearly communicate information about such issues to public health workers. Public health is far more complex than merely applying epidemiology.

Effective health promotion and clinical care for large people.

Health and fitness professionals most often approach health care for large people in the context that health improvement can only be attained through weight loss. Unequivocal acceptance of the notion that thinness equals health and fitness presents an obstacle for large people who want to improve their health through lifestyle changes in eating and activity patterns and also weakens the working relationship between the health care professional and the large client. Since the health benefits of exercise and sound nutrition are significant for people of all sizes, the strategy for health care professionals should be to assist people of all sizes in eating healthier and becoming more active. Because large people face even more barriers to exercise than smaller people, we address the special needs of large people trying to become more physically active, outline an approach sensitive to their needs, and suggest how health and fitness professionals can improve their effectiveness with this population.

Biopersistence of synthetic vitreous fibers and amosite asbestos in the rat lung following inhalation.

Fiber biopersistence as a major mechanism of fiber-induced pathogenicity was investigated. The lung biopersistence of 5 synthetic vitreous fibers (SVFs) and amosite asbestos was evaluated using the rat inhalation model. In contrast to several previous studies, this study examined fibers that dissolve relatively slowly in vitro at pH 7.4. Fisher rats were exposed for 5 days by nose-only inhalation to refractory ceramic fiber (RCF1a), rock (stone) wool (MMVF21), 2 relatively durable special application fiber glasses (MMVF32 or MMVF33), HT stonewool (MMVF34), amosite asbestos, or filtered air. Lung burdens were analyzed during 1 year post-exposure. Fiber aerosols contained 150-230 fibers/cc longer than 20 micrometer (>20 micrometer). On post-exposure Day 1, long-fiber lung burdens for the 6 test fibers were similar (12-16 x 10(5) fibers/lung >20 micrometer). After 1 year, the percentage of fibers >20 micrometer remaining in the lung was 0.04-10% for SVFs but 27% for amosite. Lung clearance weighted half-times (WT1/2) for fibers >20 micrometer were 6 days for MMVF34, 50-80 days for the other 4 SVFs, and >400 days for amosite. This study and 3 previous studies demonstrate a broad range of biopersistences for 19 different SVFs and 2 asbestos types. Ten of these fibers also have been (or are being) tested in chronic inhalation studies; in these studies, the very biopersistent fibers were carcinogenic (amosite, crocidolite, RCF1, MMVF32, and MMVF33), while the more rapidly clearing fibers were not (MMVF10, 11, 21, 22, and 34). These studies demonstrate the importance of biopersistence as an indicator of the potential pathogenicity of a wide range of fiber types.

Screening for chlamydial infection. A model program based on prevalence.

BACKGROUND: Chlamydial infection accounts for substantial health care costs. The high frequency of asymptomatic infections necessitates screening to detect affected persons. Selective screening using risk assessment criteria attempts to target limited resources to women at increased risk. However, most risk assessment criteria have not accounted for prevalence of infection. OBJECTIVES: To describe currently available screening options, to demonstrate the relationship between prevalence and probability of infection, and to propose a model program incorporating clinic prevalence in selective screening decisions. STUDY DESIGN: A simple model demonstrating the relationship between clinic prevalence, a risk score based on risk assessment, and probability of infection was developed using basic clinical epidemiological principles. RESULTS: The probability of infection can be estimated from the clinic prevalence and risk score. If the estimated probability of infection exceeds previously established test thresholds, laboratory testing is warranted. As the clinic prevalence increases, the risk score necessary to justify laboratory testing decreases. Thus, the cutoffs for risk assessment criteria should be adjusted to account for clinic prevalence. In the proposed model program, the availability of resources, such as the number of tests available to a screening program, can be accommodated by appropriate adjustment of thresholds for laboratory testing. CONCLUSION: The prevalence-based chlamydial screening program may provide a pragmatic strategy for areas with limited resources.

Monitoring behavioral changes in diabetes care with the diabetes self-management record.

An evaluation instrument called the diabetes self-management record has been developed to better document the positive behavioral changes associated with diabetes education programming. This record is a simple behavior monitoring system that awards points for positive behaviors associated with exercise, glucose monitoring, and nutrition management. A group of 39 adults with diabetes monitored their behaviors with the record prior to, immediately after, and 4 to 6 weeks following a diabetes education programming course. Overall diabetes management scores were higher (mean +/- SEM = 56.2 +/- 3.5 vs 66.3 +/- 2.9) following the educational intervention, as well as specific behavioral scores for exercise, glucose monitoring, fat consumption, refined sugar/carbohydrate consumption, and eating behavior. These behaviors were maintained for at least 4 to 6 weeks postprogramming. The diabetes self-management record can be used as an adjunct to diabetes education programming, as an evaluator of the educational intervention, and/or as a behavior monitoring tool for diabetes self-management.

Diagnosis and screening of HIV/AIDS using clinical criteria in Tanzanian adults.

The clinical utility of the World Health Organization (WHO) clinical case definition (CCD) of acquired immune deficiency syndrome (AIDS) in Africa, several proposed modifications of the WHO CCD, and two proposed screening algorithms for human immunodeficiency virus (HIV) infection were examined in adult medical inpatients in Dar es Salaam, Tanzania. Sensitivity, specificity, and positive and negative predictive values were determined for the CCDs and screening algorithms. Multivariable analysis identified factors with high accuracy for HIV infection. Of 223 patients enrolled in the study, 95 were seropositive for HIV infection. The WHO CCD and the modified CCDs had low sensitivities (14.7-32.6%) but high specificities (95.3-99.2%) and positive predictive values (83.8-94.7%). The screening algorithms had moderate sensitivities (66.3-77.9%) and poor specificities (46.1-79.7%). Multivariable analysis consistently identified oral candidiasis and lymphadenopathy as the best predictors of HIV infection. Although patients with asymptomatic or early HIV infection may be missed by clinical criteria, in a high prevalence population, AIDS may be diagnosed accurately clinically because of the effect of prevalence on the positive predictive values of the CCDs. Furthermore, selection of patients for HIV serologic testing may be guided by simple combinations of clinical features.

Cryptococcus neoformans fails to induce nitric oxide synthase in primed murine macrophage-like cells.

Nitric oxide (NO) is a microbiostatic gas generated by activated murine macrophages. Cytokine signals, gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) act synergistically to induce production of a macrophage nitric oxide synthase (NOS). A variety of intracellular pathogens, when recognized by macrophages primed with IFN-gamma, induce NOS by eliciting TNF-alpha secretion, which then functions as a positive autocrine signal. In cell culture assays, a murine macrophage cell line (J774), primed with IFN-gamma, was tested for NOS induction upon challenge with virulent Cryptococcus neoformans. C. neoformans failed to induce macrophage NOS as measured by nitrite production. This was true irrespective of the C. neoformans-to-J774 ratio. Other nonpathogenic Cryptococcus species likewise failed to induce NOS, yet Saccharomyces cerevisiae, Histoplasma capsulatum, and Candida albicans were efficient inducers of NOS. Conditions which promoted attachment and/or phagocytosis of C. neoformans did not lead to NOS induction (including opsonization with specific antibodies against C. neoformans). Assays for transcriptional repressors of NOS were negative. Tests for consumption of nitrite by measurement of additional products of NOS induction were negative. No TNF-alpha was detected by enzyme-linked immunosorbent assay in supernatants from C. neoformans-J774 cocultures. A mutant C. neoformans strain with a minimal, but visible, polysaccharide capsule also failed to induce NOS; however, several nonencapsulated mutants of C. neoformans did induce NOS. Failure of C. neoformans to act as an inducer of NOS may be related to the virulence of this pathogen in mice; C. neoformans is a unique example of a facultative intracellular pathogen which fails to induce NOS in primed macrophages. The mechanism appears to involve the failure of TNF-alpha secretion once the macrophage comes in contact with the fungus. The presence of the polysaccharide capsule appears to mask the signal necessary for TNF-alpha secretion and, ultimately, NOS induction.

Pulmonary toxicity of inhaled polypropylene fibers in rats.

This study was initiated to assess the pulmonary toxicity of a polyolefin fiber composed of polypropylene in male Fischer 344 rats after 90 days of inhalation exposure. To increase fiber respirability in the rodent, polypropylene fibers were size-selected before aerosolization to have a geometric mean diameter of 1.6 microns (46% < 1 micron) and a geometric mean length of 30.3 microns. Three groups of animals were exposed in nose-only inhalation chambers, 6 hr/day, 5 days/week, for 90 days to 15, 30, or 60 mg/m3 of polypropylene, or filtered air (negative control). Microscopic examination of the polypropylene fiber-exposed lungs revealed that, at all time points examined in the study, there was a dose-dependent increase in pulmonary macrophages. These minimal or mild increases in cellularity appeared to be reversible, especially at the lower doses 30 days post exposure. No fibrosis was observed in any of the groups. A strong correlation was found between the external exposure concentration, the time of exposure, and the lung fiber burden. The number of partially degraded (segmented) fibers within the lung increased with the exposure concentration and period of exposure, as well as with the period of recovery after termination of exposure at 90 days. Fibers were recovered from exposed lungs using a hypochlorite digestion technique.