Treatment outcome and follow-up of multidrug-resistant tuberculosis patients, West Coast/Winelands, South Africa, 1992-2002.

SETTING: Brooklyn Chest Hospital, Western Cape, South Africa. OBJECTIVE: To evaluate the treatment outcome and 2- and 5-year follow-up of patients treated for multidrug-resistant tuberculosis (MDR-TB) with individualized regimens. DESIGN: Retrospective cohort study of all MDR-TB patients starting treatment during 1992-2002. Patients were evaluated every 6 months for 2 years after treatment and at 5 years when possible. RESULTS: Over 11 years, 491 (66%) of 747 MDR-TB patients received treatment with two or more second-line drugs; 239 (49%) were cured or completed treatment, 68 (14%) died, 144 (29%) defaulted from treatment, 27 (5%) failed, 10 (2%) transferred out and 3 (<1%) remained on treatment. Only 176 (36%) were tested for human immunodeficiency virus and 15 were positive. The proportion with a successful MDR-TB treatment outcome declined over time, while the proportion who defaulted remained stable. Among 410 patients who had not transferred out or died, 281 (69%) had 2-year data available: 185 (66%) were cured or completed treatment, 32 (11%) were retreated for TB and 64 (23%) died. CONCLUSIONS: Under program conditions in the West Coast/Winelands District, default rates were high and treatment success rates low. Outreach strategies for MDR-TB treatment should only be implemented if adequate resources are committed to the program.

Dynamic heterodimer-functionalized surfaces for endothelial cell adhesion.

The functionalization of hydrogels for receptor-mediated cell adhesion is one approach for targeted cell and tissue engineering applications. In this study, polyacrylamide gel surfaces were functionalized with specific cell adhesion ligands via the self-assembly of a peptide-based heterodimer. The system was comprised of a cysteine-terminated monomer, A (MW approximately 5400), grafted to the polyacrylamide gels and a complementary ligand presenting monomer, B(X) (MW approximately 5800) that was designed to heterodimerize with A. Two ligand presenting monomers were synthesized: one presenting the RGDS ligand, B(D), for receptor-mediated cell adhesion, and the other, a control monomer presenting the nonadhesive RGES ligand, B(E). Assembly of the peptide pair A-B(X) by association of the monomers into a coiled coil was verified by circular dichroism in solution. Binding studies were conducted to determine the dissociation constant of the pair A-B(X), which was found to be K(D) approximately 10(-8) m. Polyacrylamide gels functionalized with A-B(X) heterodimers were evaluated for cell adhesion using bovine aortic endothelial cells (BAECs). Endothelial cells cultured on the A-B(D) functionalized surfaces demonstrated typical cell morphologies and expected spreading behavior as a function of the density of RGDS ligand, calculated as the amount of B(D) associated with grafted A on the surface of the gels. In contrast, A-B(E) linked surfaces supported no cell adhesion. The adhesion of the substrate was dynamically altered through the reassembly of A-B(X) dimers as B(D) molecules in the solution replaced B(E) molecules at the substrate. The molecular constructs described here demonstrate the potential to design a broad family of switchable peptides that impart the dynamic control of biofunctionality at an interface, which would be useful for precise manipulation of cell physiology.

Interplay between rolling and firm adhesion elucidated with a cell-free system engineered with two distinct receptor-ligand pairs.

The firm arrest of leukocytes to the endothelium during inflammation is known to be mediated by endothelial intercellular adhesion molecules (ICAMs) binding to activated integrins displayed on leukocyte surface. Selectin-ligand interactions, which mediate rolling, are believed to be important for facilitating firm adhesion, either by activating integrins or by facilitating the transition to firm adhesion by making it easier for integrins to bind. Although leukocytes employ two distinct adhesion molecules that mediate different states of adhesion, the fundamental biophysical mechanisms by which two pairs of adhesion molecules facilitate cell adhesion is not well understood. In this work, we attempt to understand the interaction between two molecular systems using a cell-free system in which polystyrene microspheres functionalized with the selectin ligand, sialyl Lewis(X) (sLe(X)), and an antibody against ICAM-1, aICAM-1, are perfused over P-selectin/ICAM-1 coated surfaces in a parallel plate flow chamber. Separately, sLe(X)/P-selectin interactions support rolling and aICAM-1/ICAM-1 interactions mediate firm adhesion. Our results show that sLe(X)/aICAM-1 microspheres will firmly adhere to P-selectin/ICAM-1 coated surfaces, and that the extent of firm adhesion of microspheres is dependent on wall shear stress within the flow chamber, sLe(X)/aICAM-1 microsphere site density, and P-selectin/ICAM-1 surface density ratio. We show that P-selectin's interaction with sLe(X) mechanistically facilitates firm adhesion mediated by antibody binding to ICAM-1: the extent of firm adhesion for the same concentration of aICAM-1/ICAM-1 interaction is greater when sLe(X)/P-selectin interactions are present. aICAM-1/ICAM-1 interactions also stabilize rolling by increasing pause times and decreasing average rolling velocities. Although aICAM-1 is a surrogate for beta(2)-integrin, the kinetics of association between aICAM-1 and ICAM-1 is within a factor of 1.5 of activated integrin binding ICAM-1, suggesting the findings from this model system may be insightful to the mechanism of leukocyte firm adhesion. In particular, these experimental results show how two molecule systems can interact to produce an effect not achievable by either system alone, a fundamental mechanism that may pervade leukocyte adhesion biology.

Drug-resistant tuberculosis: worldwide trends, problems specific to Eastern Europe and other hotspots, and the threat to developing countries.

Although it had been appreciated that high levels of antituberculous drug resistance existed in some regions of the world, the full extent of the problem was not known. A combined initiative by the World Health Organization and the International Union Against Tuberculosis and Lung Disease was launched in 1994 to address this. A second report was issued in March 2000, in which surveillance of drug resistance had been extended to 72 countries and regions. A number of drug resistant "hotspots," where there are high levels of combined multidrug-resistant tuberculosis (> 3% prevalence), have been identified. Particular areas of concern are countries of the former Soviet Union, India, and China, because these countries have the highest burden of multidrug-resistant tuberculosis. For the first time, information on trends in global drug resistance is available.

A prospective, randomized, multicenter comparative study of clinafloxacin versus a ceftriaxone-based regimen in the treatment of hospitalized patients with community-acquired pneumonia.

In an open-label, phase 3, randomized, multicenter study, clinafloxacin (200 mg/d) was compared to ceftriaxone (2 g/d; with or without erythromycin) in 527 patients with acute community-acquired bacterial pneumonia (CAP). Primary efficacy parameters were clinical cure rate and microbiologic eradication rates (by pathogen and by patient) determined 5-9 d post-therapy (test of cure; TOC). Clinical cure rates at TOC for the 2 treatment groups were equivalent in the intention-to-treat (clinafloxacin 79.3, ceftriaxone 78.6%), clinically evaluable (clinafloxacin 88.1, ceftriaxone 85.0%), modified intention-to-treat (clinafloxacin 82.6, ceftriaxone 86.9%) and microbiologically evaluable populations (clinafloxacin 86.2, ceftriaxone 86.2%). Microbiologic eradication rates were similar in the 2 treatment groups. Both drugs were tolerated. Treatment of hospitalized CAP patients with clinafloxacin is a reasonable choice, especially when a resistant pathogen is anticipated.

Drug-resistant tuberculosis.

There is increasing concern in many countries about the problem of drug-resistant tuberculosis, particularly so because no new classes of drugs have been developed for the treatment of tuberculosis since the 1960s. Although drug resistance is thought to be fairly common in some countries and rare in others, the global extent of this condition is not precisely known. This problem is currently being investigated by a combined initiative of the World Health Organization and the International Union Against Tuberculosis and Lung Disease. Recently, there have been advances in the understanding of the genetic basis of drug-resistant tuberculosis. With the sequencing of the whole genome of Mycobacterium tuberculosis, the possibility of new targets for drug development has emerged. For the present, however, cure rates on average remain modest, and nonadherence with chemotherapy remains a major problem. Drug resistance is a man-made problem and efforts to prevent it through directly observed therapy, short course are essential.

Transition from paediatric to adult care for persons with cystic fibrosis: patient and parent perspectives.

OBJECTIVES: To gauge the perspectives of adolescents and adults with cystic fibrosis (CF) and their parents regarding the transition from paediatric to adult-oriented health care. METHODS: Cross-sectional survey using an anonymous, semi-structured questionnaire. The study population consisted of adolescents and adults attending a paediatric and an adult CF clinic in Cape Town, South Africa and their parents. RESULTS: Forty-seven of the 61 subjects completed the questionnaire (response rate 77%). Autonomy in health care was 'extremely important' to most persons with CF. Transfer at the age of 16-18 years of age was the preferred option for most respondents. Whereas over 80% of parents felt their children needed more CF-related information, only 38% of adolescents expressed this need (P < 0.05). Adolescents also reported little need for general health information. More than 80% of respondents were 'unsure' about transfer. Over 90% felt that a transition clinic would be useful. As viewed by the respondents, its main purpose would be to provide information about the adult clinic and an opportunity to meet the CF doctor in the adult clinic. CONCLUSION: There are significant concerns about the transition process in this population. Given the expressed need for autonomy and a transition clinic, the basis for a smoother transition in the future has been laid.

Tuberculous tenosynovitis and carpal tunnel syndrome as a presentation of HIV disease.

We describe a patient who presented with carpal tunnel syndrome secondary to tuberculous tenosynovitis and who was subsequently shown to have HIV infection. Recognition of this atypical presentation of tuberculosis is important for early, effective treatment.

A comparative study of levofloxacin and ceftriaxone in the treatment of hospitalized patients with pneumonia.

A multinational, multicentre, open, randomised study in hospitalised patients with pneumonia compared levofloxacin 500 mg twice daily with ceftriaxone 4 g i.v. once daily. Levofloxacin patients started on i.v. treatment and switched to oral on d 3-5 of therapy if signs and symptoms had improved. The minimum treatment duration was 5 d, except for treatment failure, and the median 8 d. The primary efficacy analysis was based on the per-protocol assessment of the clinical cure rate determined 2-5 d after the end of treatment in the per-protocol (PP) population (levofloxacin 127, ceftriaxone 139). Of 625 patients enrolled and randomized, 6 received no treatment, giving an intention-to-treat (ITT) population of 619 (levofloxacin 314, ceftriaxone 305). At the clinical endpoint, 2-5 d after the end of treatment, the cure rates for levofloxacin and ceftriaxone were similar in both the ITT (76% and 75%, respectively) and PP (87% and 86%, respectively) populations. Both drugs were well tolerated. Twice-daily levofloxacin 500 mg, either i.v. or as sequential i.v./oral therapy, was as effective as i.v. once-daily ceftriaxone 4 g in the treatment of hospitalized patients with pneumonia and offers the advantage of sequential therapy.

Differential gene expression in response to adjunctive recombinant human interleukin-2 immunotherapy in multidrug-resistant tuberculosis patients.

Administration of low-dose recombinant human interleukin 2 (rhuIL-2) in combination with multidrug chemotherapy to patients with multidrug-resistant tuberculosis (MDR TB) induces measurable changes in in vitro immune response parameters which are associated with changes in the clinical and bacteriologic status of the patients. To determine the molecular basis of these changes, we have used semiquantitative reverse transcriptase-initiated PCR (RT-PCR) and differential display technology. During rhuIL-2 treatment of MDR TB patients, decreased levels of gamma interferon (IFN-gamma) mRNA in peripheral blood mononuclear cells (PBMC) relative to baseline levels were observed. However, at the site of a delayed-type hypersensitivity (DTH) response to purified protein derivative of tuberculin (PPD), the expression of cellular IFN-gamma and IL-2 mRNAs was increased during rhuIL-2 therapy. Levels of other cytokine mRNAs were not significantly affected by rhuIL-2 administration. Using differential-display RT-PCR, we identified several genes expressed at the DTH skin test site which were up- or down-regulated during rhuIL-2 treatment. Cytochrome oxidase type I mRNA was increased in response to rhuIL-2 therapy relative to baseline levels, as was heterogeneous nuclear ribonuclear protein G mRNA. CD63, clathrin heavy chain, and beta-adaptin mRNAs, all of which encode proteins associated with the endocytic vacuolar pathway of cells, were also differentially regulated by rhuIL-2 administration. The differential effects of IL-2 were confirmed in vitro by using PBMC obtained from PPD-positive individuals stimulated with Mycobacterium tuberculosis and IL-2. The differential expression of genes may provide a surrogate marker for leukocyte activation at a mycobacterial antigen-specific response site and for the development of an enhanced antimicrobial response which may result in improved outcomes in MDR TB patients.

Community-acquired Staphylococcus aureus bacteraemia in patients who do not abuse intravenous drugs.

Despite advances in antimicrobial therapy and intensive care support, Staphylococcus aureus continues to cause significant morbidity and mortality. We studied community-acquired S. aureus bacteraemia in a population where intravenous drug abuse is extremely uncommon, prospectively reviewing all such patients (n = 113) admitted to Groote Schuur Hospital from February 1986 to January 1991. Overall mortality was 35%. Factors associated with poor outcome were: confusion on presentation, failure to mount a febrile response, acute renal failure, adult respiratory distress syndrome, shock, endocarditis, disseminated intravascular coagulation and platelet count of < 100 x 10(9)/l. Only confusion, acute renal failure and shock were independently associated with death by stepwise regression analysis. Skin infections were the most commonly identified source of bacteraemia (22%), but in 58% of patients the source was not determined. Twenty-six percent of patients were diabetic. Almost all patients (90%) developed one or more complications. In those who survived, therapy was generally prolonged, with a median of 70 days and range of 7-393 days, depending on the associated complications. Community-acquired S. aureus bacteraemia is a serious condition associated with a high complication rate and mortality.

Pulmonary resection as an adjunct in the treatment of multiple drug-resistant tuberculosis.

BACKGROUND: Over the past decade the incidence of pulmonary disease due to drug-resistant strains of Mycobacterium tuberculosis has increased worldwide. We reviewed our local experience to clarify the benefits and risks of pulmonary resection in the management of drug-resistant strains of Mycobacterium tuberculosis. METHODS: A retrospective review was performed of 62 patients undergoing pulmonary resection for drug-resistant strains of Mycobacterium tuberculosis between January 1990 and November 1995. RESULTS: Fifty-three percent were men and 47% women with an average age of 34 years (range, 16 to 72 years). There was one postoperative death, for a perioperative (30-day) mortality of 1.6%. Sixteen complications occurred in 14 patients for an overall morbidity of 23%. Eighteen of 24 patients (75%) who were persistently sputum positive at the time of operation immediately converted to a negative sputum smear and culture. For all patients who were sputum negative after operation 80% remain relapse-free by actuarial analysis. CONCLUSIONS: We believe that operation plays an important ancillary role in the treatment of drug-resistant strains of Mycobacterium tuberculosis. The operation can be performed with acceptable morbidity and mortality and must be combined with appropriate and well-monitored pre- and postoperative antituberculous drug therapy.

rhuIL-2 adjunctive therapy in multidrug resistant tuberculosis: a comparison of two treatment regimens and placebo.

SETTING: Low-dose recombinant human interleukin 2 (rhuIL-2) adjunctive immunotherapy in multidrug resistant tuberculosis (MDR-TB) patients. OBJECTIVE: Evaluation of the effects of daily versus pulse-administered rhuIL-2 compared to placebo. DESIGN: MDR-TB patients on best available antituberculous chemotherapy received rhuIL-2 for 30 consecutive days (daily therapy), or for 5 days followed by a 9-day 'rest', for three cycles (pulse therapy). Placebo control patients received diluent. The cumulative total dose of rhuIL-2 given to each patient in either rhuIL-2 treatment group was the same. Patient immunologic, microbiologic, and radiologic responses were compared. RESULTS: The three treatment schedules induced different results. Immune activation was documented in patients receiving daily rhuIL-2 therapy. Numbers of CD25+ and CD56+ cells in the peripheral blood were increased in these patients, but not in patients receiving pulse rhuIL-2 or placebo. In addition, 5/8 (62%) patients receiving daily rhuIL-2 demonstrated reduced or cleared sputum bacterial load while only 2/7 (28%) pulse rhuIL-2 treated and 2/8 (25%) controls showed bacillary clearance. Chest radiographs of 7/12 (58%) patients receiving daily rhuIL-2 indicated significant improvement over 6 weeks. Only 2/9 (22%) pulse rhuIL-2-treated patients and 5/12(42%) placebo controls showed radiologic improvement. CONCLUSION: Daily low dose rhuIL-2 adjunctive treatment stimulates immune activation and may enhance the antimicrobial response in MDR-TB.

A prospective randomised study in limited disease small cell carcinoma--doxorubicin and vincristine plus either cyclophosphamide or etoposide.

A prospective randomised study was undertaken in patients with limited disease small cell carcinoma of the lung (SCCL), which compared doxorubicin, 50 mg/m2, and vincristine, 2 mg i.v. (intravenously) on day 1, with either cyclophosphamide, 800 mg/m2 on day 1 (CAV) or etoposide, 60 mg/m2 i.v. on day 1 and 120 mg/m2 orally on days 2-5 (AVE). Responding patients were to receive six cycles of chemotherapy at 3 weekly intervals followed after 2 weeks by mediastinal irradiation. Response rates and toxicity were evaluated by the chi square or Fisher's exact test and survival by the logrank test. 81 patients were entered into the study, 38 of whom received CAV and 43 received AVE. In the patients treated with CAV and AVE, the overall response rate was 61% (confidence limit (CL), 45-71%) and 74% (CL, 61-87%) respectively, the complete response rate was 32% (CL, 17-47%) and 51% (CL, 36-66%), respectively (P = 0.07) and the median survival was 12 and 14.5 months, respectively (P = 0.15). In the patients treated with CAV and AVE, the incidence of grade 3 and 4 leucopenia was 29% (CL, 15-43%) and 9% (CL, 0-18%), respectively (P = 0.025). No patient developed doxorubicin cardiomyopathy. These findings support the role of etoposide in first line chemotherapy for SCCL. AVE is among the more efficacious regimens for SCCL and also has a relatively low toxicity.

Clinical and immune responses of tuberculosis patients treated with low-dose IL-2 and multidrug therapy.

The immune response to infection with M. tuberculosis depends on cytokine activation of effector cells. We therefore conducted a pilot study of recombinant human interleukin-2 (rhuIL-2) as an adjunct to multidrug therapy (MDT) to evaluate the safety of this approach and to determine whether IL-2 can enhance the cellular immune response in patients with pulmonary tuberculosis (TB). Patients included in this study presented with a wide range of extent and duration of infection, and were grouped into three categories for data analysis: (1) patients with newly diagnosed, acute-stage TB who were just beginning MDT; (2) patients who had received a minimum of 45 days MDT before the start of the study and who had responded to treatment; and (3) patients with multidrug-resistant (MDR) TB who had been on MDT for at least seven months without apparent beneficial clinical response. Twenty patients received 30 days of twice-daily intradermal injections of 12.5 micrograms of IL-2. Patients from all three groups showed improvement of clinical symptoms over the 30-day period of treatment with IL-2 and MDT. Results of direct smear for acid fast bacilli (AFB) demonstrated conversion to sputum-negative following IL-2 and MDT treatment in all newly diagnosed patients and in 5/7 MDR TB patients. (The size of the skin test response to purified protein derivative (PPD) of tuberculin increased during the 30-day IL-2 adjunctive therapy in newly diagnosed patients, but decreased or disappeared in the other two groups of treated patients.) Assays in vitro for phenotype distribution, natural killer (NK) cell activity, frequency of cells proliferating in response to exogenous IL-2, and antigen-induced blastogenesis demonstrated systemic responses to intradermally administered rhuIL-2. Levels of interferon-gamma (IFN-gamma) in plasma, peripheral blood mononuclear cell (PBMC) IFN-gamma mRNA and IFN-gamma mRNA in biopsy of site of skin test response to purified protein derivative (PPD) were highest in those patients with the most acute symptoms at the beginning of the study, and decreased during rhuIL-2 and MDT. IL-2 immunotherapy did not modify levels of mRNA expression for other cytokines. Patients receiving IL-2 did not experience clinical deterioration or significant side effects. These results suggest that IL-2 administration in combination with conventional MDT is safe and may potentiate the antimicrobial cellular immune response to TB.

The effect of irradiation on lung function and perfusion in patients with lung cancer.

PURPOSE: To prospectively study the changes in lung function in patients with lung carcinoma treated with relatively high doses of irradiation. METHODS AND MATERIALS: Lung function was assessed prior to and at 6 and 12 months following radiation therapy by a clinical dyspnea score, formal pulmonary function tests (lung volume spirometry and diffusion capacity) as well as an ipsilateral hemithorax lung perfusion scan. Changes in dyspnea score were evaluated by the chi-square and the Fishers exact test. Changes in formal lung function tests were compared with the t-test for dependent data and correlations with the t-test for independent data. Fifty-one patients were entered into the study. There were 42 evaluable patients at 6 months after irradiation and 22 evaluable patients at 12 months after irradiation. RESULTS: A worsening of dyspnea score from 1 to 2, which is clinically acceptable, occurred in 50% or more of patients. However, a dyspnea score of 3, which is a serious complication, developed in only 5% of patients. The diffusion capacity (DLCO) decreased by 14% at 6 months and 12% at 12 months) (p < 0.0001). The forced vital capacity and total lung capacity decreased between 6% and 8% at 6 months and 12 months, which was statistically significant. The forced expiratory volume in 1 s decreased between 2 and 3% at 6 month and 12 months, which was not statistically significant. The ipsilateral hemithorax perfusion decreased by 17 and 20% at 6 and 12 months (p < 0.0001). There was no correlation between the initial hemithorax perfusion, or its decrease at follow up and the decrease in DLCO. CONCLUSION: Lung irradiation results in some loss of lung function in patients with lung cancer with a projected survival of 6 months or more. The pretreatment DLCO assessment should be useful in predicting clinical tolerance to irradiation.

Mycobacterial infection in renal transplant recipients.

STUDY OBJECTIVE: To determine the prevalence and presentation of mycobacterial infection as well as the influence on outcome in graft function and patient survival in renal transplant recipients at our institution. DESIGN: A retrospective review of case records of all renal transplant recipients from 1980 to 1992. SETTING: Groote Schuur Hospital, a large teaching hospital and regional tertiary referral center in Cape Town, South Africa. PATIENTS: During the period reviewed, 857 transplants were performed. The records of 487 patients who had remained in Cape Town were examined. RESULTS: There were 22 cases of mycobacterial infection (21 confirmed or presumed Mycobacterium tuberculosis and 1 unidentified Mycobacterium other than tuberculosis). In seven cases, immunosuppression had been intensified within 3 months of diagnosis. The median time from transplantation to diagnosis was 14 months (range, 2 to 74). Chest radiograph findings included consolidation (14), miliary pattern (4), pleural effusion (3), tuberculoma (2), cavitation (2), and hilar lymphadenopathy (1). Diagnosis of tuberculosis was made on sputum smears (eight), pleural biopsy specimen (two), fine-needle aspiration (one), and fiberoptic bronchoscopy in ten cases (brushings, eight; transbronchial biopsy specimen, three). Extrapulmonary tuberculosis (in addition to pulmonary tuberculosis) occurred in five patients (tuberculous meningitis, one; renal tuberculosis, one; and dissemminated infection, four). Five of the seven patients in whom immunosuppression had been intensified had concurrent infections; two of these died and the remainder returned to dialysis within 6 months. All but one patient received three antituberculosis drugs, including rifampin and isoniazid, for between 6 and 18 months. At the end of the period of review, 12 (59 percent) patients were alive, 10 with functioning grafts and 2 receiving dialysis. Four patients died while receiving antituberculosis treatment, but death was only directly related to tuberculosis in one case. CONCLUSIONS: Tuberculosis is an important infection in renal transplant recipients in Cape Town, but disseminated disease is less common than reported elsewhere.

Changes in lung function and perfusion after irradiation in patients with lung cancer.

The changes in lung function were prospectively studied for patients with lung carcinoma who were treated with relatively high doses of irradiation. Their dyspnoea score, lung volume spirometry, diffusion capacity and ipsilateral hemithorax perfusion were measured at presentation, again between 5 and 6 months after irradiation (Group 1, 36 evaluable patients), and once more between 11 and 12 months (Group 2, 16 evaluable patients). There was a worsening of the dyspnoea score from 1 to 2, in a large percentage of patients, but only 6% developed a dyspnoea score of 3. The largest change in lung function tests was a decrease in the diffusion capacity (DLCO) to 14% at 6 months and 12% at 12 months (statistically significant, P < 0.0001 paired t-test). The forced vital capacity (FVC) and the total lung capacity (TLC) showed a lesser decrease at 6 and 12 months, and the smallest decrease, which was not statistically significant, was in the forced expiratory volume in 1 s (FEV1). There was also a statistically significant decrease in the ipsilateral hemithorax lung perfusion of 16% at 6 months and 20% at 12 months. There was a weak correlation between the decrease in the DLCO and the FEV1 at follow-up. There was no statistically significant correlation between initial perfusion or decreased perfusion and the decrease in lung function. Lung irradiation should be regarded as an ablative form of therapy, analogous to surgery, in patients with a projected survival of 6 months or more. The DLCO is the most sensitive indicator of clinical damage and its pretreatment assessment should be useful in predicting clinical tolerance to irradiation.

The spectrum of endocrine dysfunction in active pulmonary tuberculosis.

OBJECTIVE: Substantial variation in the prevalence (0-55%) of hypoadrenalism in tuberculosis (TB) has been reported. The aim of this study was to prospectively evaluate adrenal, thyroid and gonadal function in patients presenting with active pulmonary TB. DESIGN: A prospective study of 50 patients admitted to a single hospital. PATIENTS: Fifty hospitalized adults with newly diagnosed sputum positive pulmonary TB (mean age 38 years, mean body mass index 18 kg/m2, mean albumin 28 g/l) were studied. MEASUREMENTS: Adrenal reserve was assessed by intravenous tetracosactrin administration with measurement of basal and stimulated cortisol concentrations. Basal ACTH, thyroid and gonadal hormones were also measured. RESULTS: The mean basal serum cortisol was 625 nmol/l (range 394-1185). Basal plasma ACTH was undetectable (< 4.4 pmol/l) in 32, normal in 17 (mean 11.45, range 4.4-24.9 pmol/l) and elevated in one (54.2 pmol/l) subjects and did not correlate with cortisol. The mean increment in cortisol following tetracosactrin was 256 nmol/l (range 0-650) and was unrelated to basal cortisol or ACTH. All 50 patients had a stimulated plasma cortisol exceeding 550 nmol/l, indicating intact adrenal reserve. Ninety-two per cent of patients had the sick euthyroid syndrome, 72% of males had hypogonadotrophic hypogonadism and 4% of patients tested positive for the human immunodeficiency virus. CONCLUSIONS: Hypoadrenalism is uncommon in active pulmonary TB despite frequent dysfunction of the thyroid and gonadal axes.