Directly observed intermittent short-course chemotherapy in the Kathmandu valley.

SETTING: Within the national tuberculosis control programme in Nepal, cure rates of only 30%-40% were achieved using standard chemotherapy. High cure rates are particularly difficult to achieve in the Kathmandu valley, because of the mobility of the population and the large numbers of private practitioners. Short-course chemotherapy (SCC) was not used in tuberculosis (TB) control programmes in Nepal before 1991. Therefore we started our pilot programme with a fully supervised, intermittent SCC regimen. In addition we established a mycobacteriological laboratory for routine culture and susceptibility tests. OBJECTIVE: The main objective was to demonstrate the high effectiveness of a three-times weekly SCC regimen and the feasibility of directly observed treatment (DOT). DESIGN: In our new out-patient department we put all active TB patients under SCC. The duration of therapy was 9 months or longer, depending upon bacteriological and radiological needs. The results were well recorded and evaluated by central supervision. Outcome of treatment was recorded at 24-48 months. RESULTS: From January 1990 to December 1993, 771 pulmonary TB patients (618 new cases and 153 old cases) commenced treatment. Of these, 645 (84%) were cured or completed treatment, 84 (11%) defaulted, 15 (2%) died, 15 (2%) were treatment failures and 12 (3.0%) relapsed. CONCLUSION: Directly observed intermittent SCC is highly cost-effective. The results of our service programme showed that it is possible to introduce such a regimen in an urban area of Nepal.

Increased levels of soluble serum interleukin-2 receptor in extrinsic allergic alveolitis correlate with interleukin-2 receptor expression on alveolar macrophages.

In a group of 20 patients with extrinsic allergic alveolitis (10 with farmer's lung, 9 with bird-breeder's lung, and 1 with humidifier's lung), we observed increased levels of soluble serum interleukin-2 receptor (ssIL-2R) with an average of 75.2 pmol (control group average, 40.6 pmol). Analysis of bronchoalveolar lavage cells by immunocytochemistry with a CD25 antibody revealed only a slight increase to 4.2% IL-2R+ cells among alveolar lymphocytes but a pronounced rise to 21.2% IL-2R+ cells among alveolar macrophages. Furthermore, cytometry revealed a fourfold higher IL-2R expression on a per cell basis for alveolar macrophages as compared with alveolar lymphocytes. A clear-cut positive correlation (p = 0.006) was found for ssIL-2R and IL-2R+ alveolar macrophages, but only a borderline correlation was found for ssIL-2R and IL-2R+ alveolar lymphocytes (p = 0.04). The finding of a concomitant decrease of IL-2R+ alveolar macrophages and of ssIL-2R on allergen avoidance further supports the notion that alveolar macrophages may be the main source of the increased ssIL-2R in patients with extrinsic allergic alveolitis.

Concomitant modulation of serum-soluble interleukin-2 receptor and alveolar macrophage interleukin-2 receptor in sarcoidosis.

Interleukin-2 receptor (IL-2R) expression on bronchoalveolar lavage (BAL) cells was studied in patients with sarcoidosis using immune cytochemistry and cytometric analysis. A low percentage of alveolar lymphocytes (AL) was found positive for IL-2R, with 7% in patients with impaired lung function and 6% in patients with normal lung function (0.4% in control subjects). Expression of IL-2R on alveolar macrophages (AM) was considerably higher, with 25% in patients with lung function impairment compared with 14% in patients without lung function impairment (1.5% in control subjects). Serum-soluble IL-2R (ssIL-2R) was significantly elevated only in patients with impaired lung function (140.0 pM), but not in patients with normal lung function (52.2 pM; control subjects, 40.0 pM). These elevated levels of ssIL-2R positively correlated with the percentage of IL-2R positive AM (p < 0.001). Immunosuppressive treatment in three patients resulted in a decrease of IL-2R+ AM and in a decrease of ssIL-2R, whereas IL-2R+ AL were unaffected. The positive correlation and the concomitant decrease of IL-2R+ AM and ssIL-2R are consistent with the idea that in sarcoidosis with clinically apparent lung involvement, elevated levels of ssIL-2R may be derived from AM and may thus be a useful indicator of the degree of activation of these cells.

A role for IgE in extrinsic allergic alveolitis?

Receptors for the Fc portion of immunoglobulin E (IgE; CD23) can be detected on the surface of alveolar macrophages (AM) in extrinsic allergic alveolitis (EAA), using monoclonal antibodies in immunocytology. More than 50% of AM were positive in 16 of the 20 patients reported here, while the remaining 4 had 11-47% positive cells. Staining with anti-IgE antibody can, in addition, demonstrate endogenous IgE bound to the AM. This suggests that IgE might be involved in the process. Since IgE-mediated asthma is associated with bronchoconstriction, we asked whether EAA patients do in fact exhibit an obstructive component. In 3 out of 10 patients we did indeed find clearly increased airway resistance (greater than 30 kPa x s x l-1). These findings are consistent with the observation of immediate bronchoconstriction observed in some patients upon allergen challenge. Since only 1 of the 20 patients studied was a smoker, and since in the literature the majority of reported cases of EAA are in nonsmokers, we speculate that smoking may interfere with immunological processes leading to EAA.

[Tracheobronchial stents--indications and possibilities]. / Tracheobronchiale Stents--Indikationen und Möglichkeiten.

16 silicone stents and 9 expandable metallic stents (Strecker-stents) were implanted in 22 patients (16 x tumors of central bronchial tree, 6 x stenosis of benign conditions). The silicone stents were mainly implanted in the trachea and main bronchi, the metallic stents in lobar bronchi. In all cases we succeeded in implantation without complications. With both stent models an immediate relief of dyspnea and respiratory failure was achieved in all cases. The average period of follow-up is 65 days, the longest 105 days (silicone stents) respectively 306 days (metallic stents). All stents were tolerated well besides one with a feeling of intrathoracic pressure. Complications were dislocation (1 x), occlusive tumor growth (1 x), granulations (1 x), suppurative bronchitis (2 x), growth of tissue through the wall of metallic stents (1 x) and restenosis by indurated secretions (2 x). Though the long term results were well with different types of stents, which are available today, the expandable stent woven of metallic wire, seems to fit best to clinical needs.

Expression of the Fc-receptor for IgE (Fc epsilon RII, CD23) on alveolar macrophages in extrinsic allergic alveolitis.

Expression of the Fc receptor for IgE (Fc epsilon R) was analyzed on alveolar macrophages (AM) in 10 patients with extrinsic allergic alveolitis (EAA) compared with 10 patients with sarcoidosis and to 6 apparently healthy controls. By using the anti-Fc epsilon RII mAb M-L25 in immunocytochemistry experiments, we found that greater than 60% of AM in 10 of 10 patients with EAA were strongly positive, as evidenced by visual analysis in light microscopy and by cytometry. By contrast, no significant staining was detected in sarcoidosis or in controls with either method. Similar results were obtained when Fc epsilon R were identified with preformed immune complexes consisting of NIP-specific human/mouse chimeric IgE antibody plus NIP-ovalbumin. Furthermore, greater than 60% of AM in patients with EAA stained positive for IgE, demonstrating that endogenous IgE is bound to the AM. Our data suggest that IgE antibodies bound to Fc epsilon RII on AM may be involved in pathophysiology of extrinsic allergic alveolitis by activation of the AM after binding of allergen to the cell surface IgE. Furthermore, with the clearcut pattern of Fc epsilon RII expression in extrinsic allergic alveolitis it may be possible to use CD23 antibodies for differential diagnosis of inflammatory lung disease.

[Photodynamic therapy of bronchial cancer]. / Photodynamische Therapie des Bronchialkarzinoms.

Photodynamic therapy (PDT) with porphyrin derivatives (haematoporphyrin and dihaematoporphyrin äther/ester) and laser light of the wavelength 640 nm, is a new procedure for the treatment of carcinomas. This form of therapy is selective, can be applied through the bronchoscope, and is aimed at accomplishing curative elimination of central tumours of the lung. To date, we have successfully applied PDT in four selected patients. Our first patient was treated in April, 1987. The irradiation modalities and the clinical course are described.