Spinal tuberculosis: a report of five cases and a review.

Spinal tuberculosis (TB) is an uncommon occurrence in developed countries. We present five cases of spinal TB illustrating some of the problems that can be encountered in clinical practice. Delay in diagnosis due to physicians unawareness of TB as a diagnostic possibility in patients with persistent back pain was observed in two patients. A high clinical index of suspicion is, therefore, needed for diagnosis. Tuberculin skin testing was positive in four patients. Computed tomography (CT) has become the examination of choice. It allows precise location of lesions and their extension to paraspinal soft tissue. Furthermore, abscess aspiration and biopsy specimens can be obtained under CT guidance. Magnetic resonance imaging in patients with neurological involvement may provide better information than CT. Definitive diagnosis depending on histological examination, smear and culture of biopsy material, however, may be difficult to obtain. In three patients, diagnosis was based on clinical presentation and response to therapy. Antituberculosis chemotherapy was highly effective in curing all patients. Management of patients should be ensured by experts in antituberculosis chemotherapy, usually chest physicians.

Lymph node perforation into the airway in AIDS-associated tuberculosis.

A 27 year old African woman infected with the human immunodeficiency virus (HIV) presented with pulmonary complaints. Her sputum smears were positive for acid-fast bacilli (AFB). Chest roentgenogram showed right mediastinal and hilar adenopathy with a right pulmonary infiltrate. At fibreoptic bronchoscopy, mucosal infiltration with perforation and presence of thick caseum was detected in the bronchus intermedius confirming the diagnosis of a perforated lymph node. This case demonstrates that a more liberal indication of bronchoscopy helps in evaluating the impact of enlarged intrathoracic lymph nodes on neighbouring bronchi, leading to earlier detection of endobronchial tuberculosis in patients with the acquired immune deficiency syndrome (AIDS).

T-cell-epitope mapping of the major secreted mycobacterial antigen Ag85A in tuberculosis and leprosy.

Lymphoproliferation and gamma interferon (IFN-gamma) secretion in response to 28 overlapping 20-mer synthetic peptides covering the complete sequence of the mature (295-amino-acid) 85A component of the major secreted, fibronectin-binding antigen 85 complex from Mycobacterium tuberculosis and Mycobacterium bovis BCG (MTAg85A) was examined by using peripheral blood mononuclear cell (PBMC) cultures from healthy tuberculin- and lepromin-positive volunteers and from patients with tuberculosis and leprosy. Peptide recognition was largely promiscuous, with a variety of human leukocyte antigen haplotypes reacting to the same peptides. PBMC from all tuberculin-positive subjects reacted to Ag85, and the majority proliferated in response to peptide 6 (amino acids 51 to 70), peptides 13, 14, and 15 (amino acids 121 to 160), or peptides 20 and 21 (amino acids 191 to 220). PBMC from tuberculosis patients demonstrated a variable reactivity to Ag85 and its peptides, and the strongest proliferation was observed against peptide 7 (amino acids 61 to 80). MTAg85A peptides were also recognized by PBMC from healthy lepromin-positive volunteers and paucibacillary leprosy patients (again in a promiscuous manner), but despite a 90% homology between the 85A proteins of M. leprae and M. tuberculosis, the peptides recognized were different. PBMC from lepromin-positive healthy contacts reacted against peptide 2 (amino acids 11 to 30), peptide 5 (amino acids 41 to 60), and peptides 25 and 26 (amino acids 241 to 270). PBMC from paucibacillary patients reacted preferentially against peptide 1 (amino acids 1 to 20) and peptide 5. Multibacillary patients were not reactive to Ag85 or the MT85A peptides. IFN-gamma production was generally detected simultaneously with positive lymphoproliferative responses, although peptide 1 mostly stimulated proliferation and peptides 27 and 28 mostly elicited an IFN-gamma response. In conclusion, regions 41 to 80 and 241 to 295 demonstrated powerful and promiscuous T-cell-stimulatory properties, resulting in proliferative responses and IFN-gamma secretion, respectively, in the majority of reactive subjects tested in this study. These results could be of value in the development of a subunit vaccine for tuberculosis and leprosy.

Are tuberculous patients at a great risk from hypercalcemia?

The risk of tuberculous patients to develop hypercalcemia was investigated in 33 patients aged 19 to 80. Twenty-two of the 33 received no vitamin D supplements. Before antituberculous chemotherapy serum calcium corrected for albumin and urinary calcium levels were normal, serum 25-hydroxyvitamin D (25(OH)D) levels were low, but serum 1,25(OH)2D levels, oral calcium load test and intestinal 47Ca absorption were normal. After 17 to 34 days of chemotherapy serum calcium corrected for albumin and 1,25(OH)2D levels were lower without change in serum D-binding protein. In 11 patients 25(OH)D, 50 micrograms/day, was given orally for two months. 25(OH)D given three days before chemotherapy in five patients induced an increase of levels of 1,25(OH)2D which was greater than in 10 control patients with similar serum levels of 25(OH)D. When chemotherapy was added to 25(OH)D, the five patients showed high normal 1,25(OH)2D levels. The last six patients received 25(OH)D together with or after starting chemotherapy. None of the 33 patients developed hypercalcemia, even when supplemented with 25(OH)D for two months. It appears that hypercalcemia is uncommon in tuberculosis.

Humoral immune response in human tuberculosis: immunoglobulins G, A, and M directed against the purified P32 protein antigen of Mycobacterium bovis bacillus Calmette-Guérin.

The P32 protein antigen of Mycobacterium bovis BCG, identified as antigen 85A in the BCG reference system, was used to investigate the humoral immune response in human tuberculosis (TB). Immunoglobulin G (IgG), IgA, and IgM directed against P32 were measured by an enzyme-linked immunosorbent assay. Mean IgG and IgA antibody levels differed significantly (P less than 0.001) between active-TB patients (50 untreated and 52 treated) and healthy control subjects (111 unvaccinated tuberculin negative, 38 unvaccinated tuberculin positive, and 72 recently BCG vaccinated). Mean IgG antibody levels, but not mean IgA antibody levels, were higher (P less than 0.05) in patients with positive microscopic examination for acid-fast bacilli than in patients with negative microscopic examination. A positive relation was found between mean levels and the extent of disease. There was no difference in mean IgM antibody levels between patients and controls. By setting the upper normal limit at the 95th percentile of the 221 healthy subjects, the sensitivities were 46% in untreated and 63% in treated patients for IgG and 30 and 50%, respectively, for IgA. Of the untreated patients, 56% were positive for either IgG or IgA antibodies. Among the untreated patients with negative direct smear, 35% were positive for IgG and 24% were positive for IgA. When both immunoglobulin classes were combined, the serological test was positive in 47% of those patients. Neither naturally acquired tuberculin hypersensitivity nor BCG vaccination affected positivity frequencies in healthy subjects. Only active TB seemed to induce significant anti-P32 antibody levels and to be associated with positivity. A serological test with P32 as the antigen might therefore be helpful for the rapid diagnosis of TB.

Detection of lytic antimycobacterial antibodies by immune lysis of liposomes sensitized to tuberculin.

Two procedures were used in order to incorporate purified protein derivative tuberculin (PPD) from M. tuberculosis, strain H37Rv, into calcein-containing liposomes: formation of multilamellar vesicles (MLV) in a PPD solution or exposure of preformed MLV to this solution. Immune lysis of these PPD-sensitized MLV was studied in the presence of a hyperimmune anti-M. tuberculosis sheep serum using a specific pathogen-free rabbit serum as a source of complement. A 50% release of encapsulated calcein was observed spectrofluorometrically after 30 min and remained unchanged up to 2 h. The release of calcein in the absence of complement or of anti-H37Rv serum or by liposomes which did not contain PPD never exceeded 1-2%. Liposomes formed in PPD solution were more sensitive to anti-H37Rv serum than preformed liposomes exposed to PPD. Trials with human sera from ten tuberculous patients revealed the presence of specific lytic immunoglobulins. In the presence of sera from skin test negative, non-tuberculous subjects, calcein release was significantly lower. This opens the way to a new method for the study of the humoral immunity in tuberculosis.

Specific lymphoproliferation, gamma interferon production, and serum immunoglobulin G directed against a purified 32 kDa mycobacterial protein antigen (P32) in patients with active tuberculosis.

Twenty-one patients treated for active tuberculosis were examined for immune reactivity to purified protein derivative (PPD) and to a purified 32-kDa protein antigen (P32) from Mycobacterium bovis, strain BCG. Lymphoproliferation of peripheral blood leucocytes to PPD and P32 was positive in 95% and 71% of the patients respectively. A positive IFN-gamma response was detected in 62% against PPD and in 48% against P32. Low blastogenesis and IFN-gamma production were observed, especially in patients with poor general health and advanced tuberculous lesions. Twelve out of twelve (100%) of the tuberculin-positive healthy volunteers responded to PPD and P32 with mean lymphoproliferation and IFN-gamma values that were higher than in the patient group. Twelve tuberculin-negative control subjects were completely unreactive to PPD and P32 antigen. On the other hand, IgG antibodies in the serum were detected in 95% of the patients against PPD, in 77% of the patients against P32 but in none of the tuberculin-positive or negative healthy volunteers. The highest IgG levels against PPD were found in those patients with the lowest in vitro lymphoproliferation and IFN-gamma production (r = -0.54; P less than 0.05). Nonspecific interferon production following induction with Newcastle disease virus, Corynebacterium parvum, or phytohaemagglutinin was comparable in the control and patient groups. Finally, low IFN-alpha titres were detected in the serum of about 50% of the patients.

Double-blind study of glaucine in chronic cough.

Thirty-eight patients, affected by chronic cough and hospitalized in 14 different rooms, entered a double-blind cross-over trial aimed at evaluating efficacy and tolerance of single oral doses of glaucine (eo mg) versus single oral doses of codeine (30 mg) and placebo. Patients occupying the same room were administered on 3 consecutive nights, and an objective evaluation of efficacy was ensured by means of a tape recorded. The mean cough counts during the 8-h interval after drug administration were 269.3 after placebo, 241.8 after glaucine, and 201.9 after codeine (p less than 0.05). The antitussive effects of glaucine and codeine were practically superimposable up to the 6th h, when glaucine effect declined. Treatments were well tolerated by all the patients, they themselves were not able to detect any difference in cough suppression among the three treatments.

Asthma from plexiglas powders.

A patient with severe asthma induced by the inhalation of plexiglas dusts is reported. Inhalation testing against various industrial products to which he was exposed at work, showed a specific and reproducible asthmatic reaction to plexiglas dusts. Complete pulmonary investigations after positive challenge excluded associated alveolitis and demonstrated an immediate and a late obstructive response. The patient was not atopic and his clinical history did not suggest occupational disease due to chronic exposure. Reduction of the plexiglas dust exposure resulted in progressive improvement.