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Biomedical subjects

A M Bernard

Publications and source records attributed to A M Bernard.

At least 37 records · Page 2Linked to original sources
PubMed1998

Correlation between interictal regional cerebral blood flow and depth-recorded interictal spiking in temporal lobe epilepsy.

PURPOSE: Single photon emission computed tomography (SPECT) is used as an adjunctive method in preoperative localization of epileptic foci. In temporal lobe epilepsy (TLE), interictal hypoperfusion is observed in 60-70% of cases. Correlation with ictal EEG changes is observed in approximately 50-60% of cases. Relationships with interictal EEG have been studied less. We compared interictal SPECT data obtained in 20 patients with their interictal intracerebral electrical activity recorded by depth electrodes to evaluate a potential relationship. METHODS: We studied 20 sequential patients whose clinical, surface, and depth EEG data indicated seizure originating in the temporal lobe and who had interictal [99mTc]hexamethylpropylene amine oxime (HMPAO)-SPECT stereo-EEG (SEEG). Intracerebral electrodes were placed according to the patient's profile. The interictal extent of epileptiform activity allowed delineation of the irritative zone. Interictal spike frequency was also analyzed semiquantitatively. Visual and numerical SPECT analysis was performed blind to SEEG data. RESULTS: Interictal hypoperfusion was observed in 16 patients, involving the epileptogenic temporal lobe in 14. Except for 1 patient who manifested lateral temporal hypoperfusion corresponding to a mass lesion, two distinctive patterns of hypoperfusion were noted: (a) mesial hypoperfusion (5 patients), and (b) global temporal hypoperfusion (8 patients). In 8 patients, hypoperfusion had also extended into the adjacent cortex. Temporal mesial hypoperfusion was associated with spiking limited to the mesial structures, whereas global temporal hypoperfusion or hypoperfusion extending beyond the temporal lobe was associated with a similar topographic pattern of spikes. CONCLUSIONS: Comparison between SPECT and SEEG data collected in the interictal phase indicated that the extent of the hypoperfused area correlated topographically with that of the underlying irritative zone.

Adolescent↗
PubMed1997

Thymocytes in Thy-1-/- mice show augmented TCR signaling and impaired differentiation.

Thy-1, a single variable-like immunoglobulin superfamily domain anchored in the plasma membrane by a glycosyl phosphaditylinositol tail [1], is a major surface glycoprotein in adult mammalian neurons and rodent thymocytes [2]; the function of Thy-1 has remained enigmatic since its discovery [3]. Studies in vitro have implicated Thy-1 in homotypic and heterotypic cell-cell interactions [2,4]. Ligation of Thy-1 initiates transmembrane signaling pathways that lead to diverse physiological outcomes in different cells [2,5-7]. In rodents, Thy-1 is highly expressed on the surface of CD4+CD8+ double-positive immature thymocytes and downregulated in mature T cells. Here, we report that thymocytes from Thy-1-/- mice [8] had altered cell-cell contacts, and hyperresponsiveness to T-cell receptor (TCR) triggering as demonstrated by the heightened activation of p56lck, phosphorylation of TCR subunits, Ca2+ fluxes and cell proliferation. Thy-1-/- thymocytes exhibited impaired maturation from the double positive to single positive stage of thymocyte development, possibly due to inappropriate negative selection, and were prone to T lymphomas in aged mice. These observations indicate that Thy-1 negatively regulates TCR-mediated signaling and controls activation thresholds during thymocyte differentiation.

Animals↗
PubMed1997

The assessment of biomarkers to detect nephrotoxicity using an integrated database.

Groups of industrial workers exposed to heavy metals (cadmium, mercury, and lead) or solvents were studied together with corresponding control groups. The cohorts were collected from several European centers (countries). Eighty-one measurements were carried out on urine, blood, and serum samples and the results of these analyses together with questionnaire information on each individual were entered into a central database using the relational database package Rbase. After the completion of the database construction phase, the data were exported in a format suitable for analysis by the statistical package SAS. The potential value of each test as an indicator of nephrotoxicity was then assessed. Rigorous exclusion criteria were applied which resulted in the elimination of some tests and samples from the dataset. The measurable contributions of smoking, gender, metal exposure, and site were either singly or in combination assessed by biomarkers for nephrotoxicity. The parameters measured included three urinary enzymes, six specific proteins, total protein, two extracellular matrix markers, four prostaglandins and anti-GBM antibodies, and beta 2-microglobulin in serum. The most sensitive renal tests included the urinary enzymes N-acetyl-beta-D-glucosaminidase (NAG) and intestinal alkaline phosphatase (IAP), brush border antigens, and urinary low-molecular-weight proteins. Of the newer tests investigated the prostaglandins were the most promising. Different patterns of biomarker excretion were observed following exposure to lead, cadmium, or mercury. The dataset provides a unique repository of data which could provide the basis of an enlarging source of information on normal human reference ranges and on the effects of exposure to toxins and the use of biomarkers for monitoring nephrotoxicity.

Biomarkers↗
PubMed1997

Proximal tubular injury in Chinese herbs nephropathy: monitoring by neutral endopeptidase enzymuria.

Neutral endopeptidase (NEP) is a 94 kDa ectoenzyme of the proximal tubule brush border, physiologically released into the urine with apical membrane fragments. As proximal tubular atrophy was a histological hallmark of Chinese herbs nephropathy (CHN), this study firstly determined renal excretion of NEP in healthy control subjects (N = 31), in patients with CHN (N = 26) and in women having consumed Chinese herbs and whose renal function was normal but running the risk of developing CHN (N = 27). Another patient group consisted of female patients with glomerular diseases (N = 12). At the same time, measurements of urinary microproteins (Clara cell protein, retinol binding protein, beta 2-microglobulin and alpha 1-microglobulin) were performed, as indicators of tubular dysfunction. Cell damage was estimated by the excretion of N-acetyl-beta-D-glucosaminidase (NAG). In the control group, the physiological NEP enzymuria was 43.1 micrograms/24 hr (geometric mean). In CHN patients, levels of urinary NEP were significantly decreased in those with moderate renal failure (26.7 micrograms/24 hr; N = 21; P < 0.05) and almost abolished in end-stage renal failure patients (4.35 micrograms/24 hr; N = 5; P < 0.05). In patients at risk as well as in patients with glomerular diseases, urinary NEP levels were not statistically different from those observed in control subjects (40.68 micrograms/24 hr and 48.5 micrograms/24 hr, respectively). Several degrees of tubular dysfunction and injury were noted in patients groups, as attested by increased urinary microproteins and NAG excretions. Considering the data from control and CHN patients, NEP enzymuria positively correlated with individual creatinine clearance values (r = 0.76; P = 0.0001) and negatively correlated with urinary microproteins levels (r = -0.55; P = 0.00001). Finally, NEP was regularly quantitated in the urine of 6 CHN patients for a period ranging from six months to two years and in 19 patients at risk during two years, respectively. In the first group, renal function progressively deteriorated in 3 patients, leading them to renal replacement therapy after 38 to 115 weeks. Stable parameters were observed in the remaining 3 patients. A direct correlation between creatinine clearance and NEP excretion was found longitudinally in each case. In the second group, no significant change of urinary NEP levels was observed (45.9 micrograms/24 hr), in parallel with stable renal function. Taken together, these results indicate that, in CHN patients, NEP enzymuria provides a rapid and noninvasive determination of the degree of structural impairment affecting the proximal tubular population and further reflecting the severity of the renal disease. The interest of this urinary marker in monitoring the progression of other tubulointerstitial diseases remains to be assessed.

Adult↗
PubMed1997

Impact of percutaneous oestradiol gels in postmenopausal hormone replacement therapy on clinical symptoms and endometrium.

OBJECTIVE: To compare the effects on endometrium, climacteric symptoms and the menstrual cycle, and the clinical and biological tolerance of two percutaneous oestradiol gels used as hormone replacement therapy. DESIGN: A large open randomised multicentre study. SETTING: France and Belgium. PARTICIPANTS: Two-hundred and fifty-four women with an intact uterus and who had experienced a natural menopause received either Oestrogel (n = 126) or Estreva, a new formulation of oestradiol gel (n = 128), (1.5 mg of oestradiol/day) for the 24 first days of each calendar month during six consecutive months. Nomegestrol acetate (Lutenyl), a norprogesterone derivative, was administered (5 mg/day) from day 11 to day 24 of each oestradiol cycle. MAIN OUTCOME MEASURES: Examination of endometrial biopsies taken before treatment and between days 18 and 24 of the last treatment cycle, climacteric symptoms assessed using a modified Kupperman index, control of menstrual cycle evaluated by diary cards, and clinical and biological tolerance. RESULTS: Both treatments lowered the frequency and intensity of hot flushes and the global Kupperman index. 96% of the cycles were followed by withdrawal bleeding. Breakthrough bleeding or spotting resulted in premature discontinuation of treatment in one volunteer. Mastodynia occurred in 20 women and contributed to the premature termination of treatment in three of them. Endometrial biopsies taken at the end of treatment showed identical histologies in both groups, with a secretory pattern in the majority of women, and absence of hyperplasia. CONCLUSIONS: This trial confirmed that, when the two oestradiol gels tested were administered cyclically with nomegestrol acetate to postmenopausal women, they were well tolerated, effective and suitable for the treatment of oestrogen deficiency syndrome.

Administration, Cutaneous↗
PubMed1997

Ictal single photon emission computed tomography in occipital lobe seizures.

PURPOSE: Ictal single photon emission computed tomography (SPECT) has been evaluated as an adjunctive localizing technique in temporal lobe epilepsies and, to a lesser degree, in some extratemporal epilepsies. The purpose of this study was to determine whether occipital lobe seizures are associated with distinctive ictal cerebral blood perfusion (rCP) patterns. METHODS: SPECT was used with the tracer 99mTc HMPAO to image ictal rCP in 6 patients in whom clinical, EEG, and imaging data indicated occipital lobe seizures. RESULTS: Two patterns of rCP were seen. Four patients had hyperperfusion that was restricted to the occipital lobe, and two patients had hyperperfusion of the occipital lobe and the ipsilateral mesial temporal lobe, with hypoperfusion of the lateral temporal lobe. The latter 2 patients had clinical and surface EEG evidence of temporal lobe involvement in the seizure discharge. CONCLUSIONS: Ictal rCP patterns in occipital lobe seizures are distinct from those in temporal lobe seizures and may vary according to whether or not ipsilateral temporal lobe structures are involved in the ictal discharge.

Adolescent↗
PubMed1997

Diabetes in urban African-Americans. IX. Provider adherence to management protocols.

OBJECTIVE: Staged diabetes management should permit glycemic goals to be attained in a timely manner, but the success of such an approach requires conformity by health care providers. To test performance, we analyzed the adherence of practitioners to a protocol for staged management of NIDDM patients. RESEARCH DESIGN AND METHODS: Records of patients treated at the Grady Memorial Hospital Diabetes Clinic were reviewed retrospectively over a 3-year period. For each patient, intensification of therapy was indicated if fasting plasma glucose was > 7.8 mmol/l and a prior HbA1c was > 7.0%. Protocols dictated a progression from dietary therapy alone to increasing dosages of sulfonylureas to increasing dosages of insulin. Patients were seen at bimonthly intervals. RESULTS: During the 3-year period, 1,051 patient visits met protocol criteria for intensification. Adherence to the protocol improved significantly in the 3rd year compared with the first 2 years (30, 31, and 47% adherence in the 1st, 2nd, and 3rd years, respectively). Patients treated with diet alone were significantly less likely to have their therapy intensified than patients on sulfonylureas or insulin (intensification rates 25, 41, and 47%, respectively). In the management of patients treated with diet alone, practitioners were reluctant to intensify therapy at early visits, but were more likely to do so later, 19% of patients beyond goal range at the 2-month visit were started on pharmacological therapy vs. 28% at the 4-month visit, and 39% at the 6-month visit (P < 0.01). In contrast, there was no significant difference in the frequency of therapy intensification between early and late visits for patients on sulfonylureas or insulin. Practitioners appeared to base the decision to intensify on the fasting plasma glucose level more than on the most recent HbA1c. Age did not appear to be a significant factor in the decision to intensify. CONCLUSIONS: Although staged management protocols constitute critical tools to achieve glycemic goals, the adherence of health care providers may be suboptimal. Special efforts may be needed to assure compliance.

Black or African American↗
PubMed1996

Effect of oral protein load on urinary protein excretion in workers exposed to cadmium and to lead.

An acute oral protein load causes a transient hyperfiltration that might reveal a loss of glomerular permselectivity properties. The effect of an oral protein load on the urinary excretion rate of albumin (UAE), beta-2-microglobulin (UB2MGE), and retinol-binding protein (URBPE) was thus examined in cadmium- and lead-exposed workers. The results show a transient increase in UB2MGE and URBPE without relevant changes in UAE. These changes were also observed in control groups and are due to competitive inhibition of tubular protein reabsorption by absorbed cationic amino acids. These results do not support the hypothesis that the acute protein load test is of great utility in revealing a silent glomerular filtration disturbance in lead- or cadmium-exposed workers. However, it might disclose imminent renal tubular dysfunction in cadmium workers not yet showing increased microproteinuria under baseline conditions.

Adult↗
PubMed1996

Comparing the hospitalizations of transfer and non-transfer patients in an academic medical center.

BACKGROUND: By accepting and caring for patients transferred from other institutions, academic medical centers have been able to develop comprehensive training and research programs. Whether academic institutions can continue to do this in the future is questionable. To the extent that transfer patients are more complex and severely ill than non-transfer patients, they are likely to consume more resources, and in managed care payment systems, they could place accepting hospitals in financial jeopardy. METHOD: Between July 1989 and December 1993, the internal medicine, surgery, and pediatrics services of the 880-bed University Hospital of the University of Michigan accepted 8,740 patients from other hospitals. The hospitalizations of these patients were compared with those of the 76,047 non-transfer patients on these services. The statistical methods used were Student's t-test, chi-square, Cochran-Mantel-Haenszel chi-square, and analysis of variance. RESULTS: The hospitalizations of the transfer patients were more complex and resource-use intensive. The transfer patients were more likely (p<.0000) to be length-of-stay outliers as defined by Medicare standards (28% vs 10%) and to suffer in-hospital death (9.4% vs 2.5%). After case-mix adjustment and exclusion of length-of-stay outliers, transfer patients on the three services (surgery, medicine, and pediatrics) remained in the hospital 1.62, 1.15, and 0.84 days longer (p<.0001) than non-transfer patients. Ancillary-service resource use was assessed using a relative-value-unit (RVU) scale based on direct-cost dollars. The transfer patients' case-mix-adjusted resource use exceeded that of the non-transfer patients by 1,155,850 and 957 RVUs for surgery, pediatrics, and medicine (p<.0001). Although the transfer patients were more likely to have Medicaid insurance, the differences in lengths of stay and use of ancillary services persisted throughout all insurance groups. Indeed, transfer status, compared with age, sex, and insurance status, was the best predictor of high resource use. CONCLUSION: The transfer patients stayed longer and consumed more hospital resources than did the non-transfer patients. Age, sex, case-mix, and insurance status did not account for these differences. To limit the financial liability that transfer patients pose, academic medical centers could be forced to abandon their traditional role of caring for such patients. The consequences of this possibility should be explored.

Academic Medical Centers↗
PubMed1996

Clara cell protein (CC-16) and surfactant-associated protein A (SP-A) in asbestos-exposed workers.

Asbestos-exposed workers (Asb) can sometimes develop lung impairments resembling idiopathic pulmonary fibrosis (IPF). Smoking is often a troubling confounder in the natural history of these lung diseases. Distal airspace epithelial cells, which are also altered in asbestosis, secrete Clara cell protein (CC-16, also designated CC-10) and surfactant-associated protein A (SP-A). By inhibiting phospholipase A2 (PLA2), CC-16 and SP-A are putative candidates for controlling lung inflammatory events. Both were measured with PLA2 activity in alveolar fluids (and sera for CC-16) of smoker and nonsmoker Asb and compared with smoking-matched normal subjects (N). CC-16 (in mg/L) was slightly increased in Asb and affected by smoking: nonsmoker Asb: 3.1 +/- 0.5 vs nonsmoker N: 1.9 +/- 0.2 (p < 0.05), smoker Asb: 1.7 +/- 0.3 vs smoker N: 0.6 +/- 0.1 (p < 0.05). SP-A (in microgram/mL) was enhanced in Asb but not affected by smoking: 5.4 +/- 1.5 in Asb vs 1.6 +/- 0.4 in N (p < 0.05), whereas SP-A to phosphorus ratio was increased in Asb but affected by smoking. CC-16 to albumin and CC-16 in serum to alveolar fluid ratios were altered by cigarette consumption in Asb (p < 0.05 vs N). Secretory PLA2 activity was slightly enhanced in Asb (p < 0.05 vs N). All data were similar between stages of disease. In summary, alveolar CC-16, SP-A, and secretory PLA2 activity were increased in Asb. Smoking affected several parameters. By this habit, Asb might reinforce lung profibrotic factors and increase their risk in developing lung alterations resembling IPF.

Adult↗
PubMed1996

[Pulmonary metastases with a prolonged development. Two cases of thyroid cancers].

The authors report two cases of differentiated carcinoma of the thyroid with pulmonary involvement showing as miliary shadowing radiologically which preceded the diagnosis of the thyroid neoplasm by 35 and 6 years respectively. The two patients had undergone cervical radiotherapy in infancy for lymphadenopathy whose aetiology had not been determined. The scintigraph with iodine 131 showed tht in two cases there was a bilateral and diffuse pulmonary uptake in keeping with pulmonary lesion of metastatic origin. Our observations recall the possibility of a slow evolution of pulmonary metastases and carcinoma of the thyroid and the role of cervical irradiation in the development of such cancers. With miliary shadowing a metastatic origin, in particular that of the thyroid, should be considered and in the majority of cases the proof could be supported using iodine 131 scintigraphy. The delay in appearance of pulmonary metastases during the course of cancer of the thyroid is variable. They occur most often after the initial diagnosis or more rarely preceding the discovery of a primary thyroid cancer. The pulmonary metastases may be asymptomatic. This neoplasm may benefit from a specific effective therapy and prolonged remissions have been described even with metastases.

Adult↗
PubMed1996

Ictal cerebral blood flow in seizures originating in the posterolateral cortex.

UNLABELLED: In selecting patients for epilepsy surgery, it is important to distinguish mesial temporal seizures from seizures originating in the posterolateral cortex. We studied ictal cerebral perfusion in five patients with complex partial seizures with clear posterior EEG ictal onsets and clinical seizures semiology suggesting seizure origin in the posterolateral cortex. METHODS: Ictal SPECT was performed during video EEG monitoring using 99mTc-HMPAO as a cerebral perfusion tracer and a rotating gamma camera to acquire images. RESULTS: Three patterns of ictal hyperperfusion were seen: pattern A = temporoparieto-occipital junction extending into the lateral temporal cortex, involving the mesial temporal cortex and basal ganglia to a lesser degree and a small area of hyperperfusion in the contralateral parietal cortex (two patients); pattern B = pattern A but with no hyperperfusion of the mesial temporal cortex (one patient); and pattern C = localized hyperperfusion in the area of the temporoparieto-occipital junction (two patients). CONCLUSION: Our results suggest distinct patterns of ictal perfusion in seizures with posterolateral ictal EEG onsets. Ictal SPECT may be useful in distinguishing such seizures.

Adolescent↗
PubMed1995

Biokinetics and stability aspects of biomarkers: recommendations for application in population studies.

The knowledge of the toxicokinetics of chemicals is an important prerequisite of biological monitoring of exposure. Kinetic data allow to determine whether the test is likely to reflect the recent exposure or to integrate the exposure over a certain period of time. They are necessary to select the appropriate parameter, biological specimen and sampling time by taking into account the type of exposure and the sensitivity of the analytical method. Various mathematical models have been developed to provide a global and quantitative description of the behavior of the chemical in the organism. In practice, however, the parameter to which one usually refers is the elimination half-life of the biomarker which reflects both the affinity of the chemical for the biological matrix and the efficiency of excretory or metabolic processes. Since chemically-induced diseases usually develop following repeated exposures over many years, markers which are the most useful for population studies are those integrating the dose received by the organism or by the target organ(s) over a toxicologically relevant period of time exposure. For a reliable application of biological monitoring in population studies, information must be collected on the stability of the biomarker and the precautions to be taken during transportation and storage of samples. The factors most likely to affect the stability of the parameter are evaporation, chemical deterioration, precipitation, adsorption on vessel surfaces and contamination. This paper formulates a series of practical recommendations to prevent or minimize variations in the pre-analytical phase which might be caused by these factors.

Biomarkers↗
PubMed1995

Renal effects in children living in the vicinity of a lead smelter.

A cross-sectional study was carried out to determine whether environmental exposure of children to lead may cause renal effects. The study involved a total of 195 children aged 12 to 15 years. One hundred forty-four children (63 boys and 81 girls) were recruited from two schools in the vicinity of a lead smelter and 51 (25 boys and 26 girls) from a school in a rural area. Compared to their referents, boys and girls from the two schools in the polluted area had significantly higher levels of lead in blood (PbB) but similar levels of cadmium (CdB) and zinc protoporphyrins (ZPP). The functional integrity of the kidney was assessed by measuring the urinary excretion of beta 2-microglobulin, Clara cell protein, retinol-binding protein (RBP), albumin and beta-N-acetyl-D-glucosaminidase. The most significant and consistent finding of the study was that children from the two schools in the polluted area showed a significant elevation of the urinary excretion of RBP that paralleled the level of lead in blood or in the dust collected on the school playgrounds. A similar pattern was observed for the prevalence of elevated values of urinary RBP which increased from 3.9% in the control area up to 17% in the most polluted school. Urinary RBP was found to be associated with PbB (partial r2 = 0.046, P = 0.005) in a stepwise regression analysis testing also the influence of age, sex, CdB, and ZPP. In conclusion, the present study suggests that lead contaminating the environment may cause slight effects on the proximal tubule function in children at exposure levels close to those associated with CNS deficit.

Adolescent↗
PubMed1995

The integrated inpatient management model. Lessons for managed care.

The Integrated Inpatient Management Model was a 2.5-year controlled prospective trial of using a clinical information system to direct and monitor physician and hospital practice on general medicine services of an 880-bed university hospital. For the over 2,000 admissions on both a control service and the intervention service, the mean length of stay (LOS) decreased when compared with historic norms (0.68 and 0.95 days respectively; P < 0.01 for both). This difference in mean LOS represents a savings of 580 hospital days for the intervention over the control service; (95% confidence interval, 300 to 1420 days). There also was a trend for the intervention service to have fewer LOS outliers than expected (P = 0.14). Ancillary service use decreased by 17% on both control and intervention services (a trend that disappeared after the study was terminated), while other internal medicine services experienced a 29% increase in this measure of resource use. The intervention service experienced fewer preventable deaths (P = 0.04), but there were no differences in global quality of care measures, readmission and mortality rates, and patient satisfaction. This use of a clinical information system is a prototype for the systems that will be needed for all forms of managed care.

Ancillary Services, Hospital↗
PubMed1994

Structure of the mouse dipeptidyl peptidase IV (CD26) gene.

Dipeptidyl peptidase IV (DPP IV, EC 3.4.14.5) is an ectopeptidase whose expression is modulated during thymocyte differentiation and T cell activation. We describe here the organization of the mouse DPP IV gene. This gene, which encompasses more than 90 kb, is composed of 26 exons separated by introns, the lengths of which vary from 100 bp to more than 20 kb. Reverse PCR performed on RNA from different tissues indicated that DPP IV transcripts do not contain alternatively spliced CDS sequences and, therefore, are supposed to yield a single polypeptide. However, two types of specific mRNA have been detected that differ in their 3'UTR sequences. They derive from alternative polyadenylation of the DPP IV primary transcript, since the different 3'UTR sequences are contiguous in the mouse DPP IV gene. Sequence analysis of the gene 5'-flanking region revealed several structural features found in the TATAA-box-less promoters, including a G+C-rich segment, a high frequency of dinucleotide CpG, and an imperfect symmetrical dyad. The DPP IV gene was assigned by in situ hybridization to the mouse [2C2-2D] region, which is syntenic with human chromosome 2. These data indicate that the human Dpp4 locus is located within this synteny region (i.e., 2q14-q37). The genomic organization of the mouse DPP IV gene is compared to that of classical serine proteases and serine hydrolases. As structural and mechanistic conservation in the absence of sequence similarity is the most remarkable feature among alpha/beta hydrolases [Ollis, D. L., et al. (1992) Protein Eng. 5, 197-211], we report the possible evolutionary link between the DPP IV related family and alpha/beta hydrolases.

Alternative Splicing↗
PubMed1994

Serum Clara cell protein: an indicator of bronchial cell dysfunction caused by tobacco smoking.

Clara cell protein (CC16) is a 16-kDa protein secreted by Clara cells and other nonciliated cells of both the bronchiolar and bronchial epithelium. CC16 is present in high concentrations in the respiratory tract secretions but occurs also in other fluids such as serum. In this study, CC16 has been measured in the sera from 65 female and 69 male current smokers and in a sex- and age-matched control group of 135 neversmokers. Lifetime smoking averaged (geometric mean) 12.7 (range, 0.6 to 61.3) and 17.9 (range, 0.8 to 126) pack-years in female and male smokers, respectively. A significant reduction of Clara cell protein was found in the sera of smokers of both sexes. In neversmokers serum CC16 was independent of sex but significantly increased with age. In current smokers serum CC16 was also negatively correlated with both the current and lifetime cigarette consumption and with the 24-h urinary excretion of thiocyanate. After adjustment for age, a linear dose-response relation was apparent between smoking history and serum CC16, the latter decreasing on average by about 15% for each 10 pack-year smoking history. The present study supports the concept that CC16 in serum is a marker of bronchial dysfunction caused by tobacco smoke. As CC16 appears to be a natural immunosuppressor of the respiratory tract, its decreased production might explain some inflammatory changes associated with smoking.

Adult↗