Recent Publications by CFE Educators

PURPOSE

The purpose of this work was to describe the radiographic and CT findings in patients with respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) and to correlate them with clinical, physiologic, and pathologic features.

METHOD

RB-ILD was proved pathologically in all 21 patients. Sixteen (76%) patients were current smokers, and five (24%) patients were ex-smokers. The mean cigarette consumption was 38.7 pack-years. Chest radiographs and CT scans were semiquantitatively analyzed and correlated with clinical findings, physiologic measures, and a pathologic score of disease extent.

RESULTS

The major radiographic findings were bronchial wall thickening in 16 patients (76%) and ground-glass opacity in 12 patients (57%). The predominant initial CT findings were central bronchial wall thickening (proximal to subsegmental bronchi) in 19 patients (90%), peripheral bronchial wall thickening (distal to subsegmental bronchi) in 18 patients (86%), centrilobular nodules in 15 patients (71%), and ground-glass opacity in 14 patients (67%), None of these CT findings had a significant zonal predominance. Other findings were upper lung predominant centrilobular emphysema (57%) and patchy areas of hypoattenuation (38%) with a lower lung predominance. Radiologic findings were similar in both current and ex-smokers. The amount of ground-glass opacity correlated inversely with arterial oxygen saturation ( r = -0.67, p = 0.04), and the areas of hypoattenuation correlated with alveolar-arterial oxygen gradient ( r = 0.56, p = 0.04). The extent of centrilobular nodules correlated with the extent of macrophages in respiratory bronchioles ( r = 0.53, p = 0.03) and with chronic inflammation of respiratory bronchioles ( r = 0.57, p = 0.02). The extent of ground-glass opacity correlated with the amount of macrophage accumulation in the alveoli and alveolar ducts ( r = 0.56, p 0.01 and r = 0.54, p = 0.04, respectively). At follow-up CT after steroid treatment and smoking cessation, in nine patients, the extent of bronchial wall thickening, centrilobular nodules, and ground-glass opacity had decreased, but the areas of hypoattenuation had increased (p 0.05).

CONCLUSION

The CT findings of RB-ILD are centrilobular nodules, ground-glass opacity, and air trapping. These radiologic features, in patients with a history of heavy cigarette smoking, may differentiate RB-ILD from other interstitial lung diseases.

A variety of second messenger systems have been implicated in the intracellular mechanisms of tolerance development to the analgesic actions of morphine, a mu opioid, and clonidine, an alpha-2 adrenergic receptor agonist. Here, we studied mice that carry a null mutation in the gene encoding a neuronal specific isoform of protein kinase C (PKC), namely, PKC gamma. We used the tail-flick test to construct dose-response curves before and 4 days after chronic morphine (75-mg pellets, subcutaneously (s.c.)) or clonidine treatment (0.3mg/kg, s.c., twice daily). Baseline tail-flick latencies did not differ in PKC gamma mutant and wild-type mice (3-4s). Both morphine and clonidine produced a dose-dependent suppression of the tail-flick response with an ED(50) (effective dose resulting in a 50% reduction of the control response) value (2.0mg/kg for morphine and 0.1mg/kg for clonidine) that was similar for naive mutant and wild-type mice. In contrast, after 4 days of drug delivery, mutant mice showed significantly less rightward shift in the dose-response curve to morphine (six-fold for wild-type and three-fold for mutant mice) and to clonidine (five-fold for wild-type and no shift for the mutant mice). These results indicate that PKC gamma contributes to the development of tolerance to the analgesic effects of both morphine and clonidine. Chronic morphine treatment can also result in sensitization of spinal cord neurons and increased pain behaviors following a noxious insult. To assess the contribution of PKC gamma to this process, we studied the responses of wild-type and mutant mice to an intraplantar injection of formalin (a model of persistent pain) following chronic morphine treatment. Although morphine tolerance increased formalin-evoked persistent pain behavior and Fos-LI in wild-type mice, there was no difference between placebo- and morphine-treated mutant mice, suggesting that PKC gamma also contributes to chronic morphine-induced changes in nociceptive processing.

BACKGROUND

Although noninvasive pharmacologic stress tests are widely used, their relative performance is not clear. We compared the performance of pharmacologic stress tests combined with echocardiography or nuclear imaging for the diagnosis of coronary disease.

METHODS

We performed a regression meta-analysis of published data. We included studies published between January 1975 and June 1999 in which subjects underwent echocardiographic or single-photon emission computed tomography (SPECT) stress testing with adenosine, dipyridamole, or dobutamine for diagnosis of coronary artery disease. All subjects also underwent coronary angiography. Two independent reviewers abstracted population characteristics, technical factors, methodologic factors, and results and calculated test sensitivity and specificity.

RESULTS

Eighty-two studies met the inclusion criteria. The sensitivity of dipyridamole SPECT imaging, 89% (95% CI, 84%-93%), was higher than that of dipyridamole echocardiography, but the specificity of dipyridamole SPECT imaging, 65% (95% CI, 54%-74%), was lower than that of dipyridamole echocardiography. Dipyridamole and adenosine tests had similar sensitivities and specificities. The sensitivity of dobutamine echocardiography, 80% (95% CI, 77%-83%) was similar to that of dobutamine SPECT imaging, but dobutamine echocardiography had a higher specificity, 84% (95% CI, 80%-86%) than dobutamine SPECT imaging did.

CONCLUSIONS

The findings of our study can be used to guide the selection of the optimal pharmacologic stress test for each patient. Maximum sensitivity can be attained by use of a vasodilator combined with SPECT imaging. Maximum specificity can be attained by use of a vasodilator with echocardiography. The highest combination of sensitivity and specificity can be attained with dobutamine echocardiography.

This study was designed to investigate the levels of IL-2 and its soluble receptor (sIL-2R) in bronchoalveolar lavage fluid (BALF) from patients with systemic sclerosis (SSc). We studied 18 patients with SSc and 10 healthy volunteers. Based on high-resolution computed tomography lung scans the patients were divided into two groups, those with (SSc-ILD group, n= 10) and those without (SSc group, n = 8) evidence of interstitial lung disease (ILD). Both groups showed significantly higher total cell and neutrophil counts in the BALF than controls. The SSc group also showed significantly higher levels of lymphocytes than controls. IL-2 was not detectable in BALF. The patients showed significantly higher levels of sIL-2R than controls (77.8% vs 20%, P=0.005). The median sIL-2R levels detected did not differ between the two patient groups (SSc-ILD 270 pg/ml, SSc 232 pg/ml). This study suggests that SSc patients with or without ILD have elevated levels of sIL-2R in BALF and that in some of these patients this finding could be explained by subclinical pulmonary inflammation.

The risks and benefits of structured treatment interruption (STI) in HIV-1-infected subjects are not fully understood. A pilot study was performed to compare STI with continuous highly active antiretroviral therapy (HAART) in chronic HIV-1-infected subjects with HIV-1 plasma RNA levels (VL) 400 copies per ml and CD4(+) T cells >400 per microl. CD4(+) T cells, VL, HIV-1-specific neutralizing antibodies, and IFN-gamma-producing HIV-1-specific CD8(+) and CD4(+) T cells were measured in all subjects. STIs of 1-month duration separated by 1 month of HAART, before a final 3-month STI, resulted in augmented CD8(+) T cell responses in all eight STI subjects (P = 0.003), maintained while on HAART up to 22 weeks after STI, and augmented neutralization titers to autologous HIV-1 isolate in one of eight subjects. However, significant decline of CD4(+) T cell count from pre-STI level, and VL rebound to pre-HAART baseline, occurred during STI (P = 0.001 and 0.34, respectively). CD4(+) T cell counts were regained on return to HAART. Control subjects (n = 4) maintained VL 400 copies per ml and stable CD4(+) T cell counts, and showed no enhancement of antiviral CD8(+) T cell responses. Despite increases in antiviral immunity, no control of VL was observed. Future studies of STI should proceed with caution.