Elevated anti-tuberculous glycolipid antibody titres in healthy adults and tuberculosis patients in Thailand.

OBJECTIVE: To evaluate immunoglobulin G (IgG) and immunoglobulin A (IgA) responses to tuberculous-glycolipid antigen (TBGL-IgG and -IgA) in pulmonary tuberculosis (TB) patients and healthy controls in Thailand. DESIGN: Anti-TBGL antibody titres and other TB related markers were measured in the serum samples of 24 adults with pulmonary TB (PTB), 28 healthy adults (HA), 23 children with TB (CTB) and 24 healthy children (HC). RESULT: Both TBGL-IgG and -IgA titres were significantly higher only in adult PTB cases compared to controls (P < 0.001 for all). TBGL-IgG was highly sensitive (92%) in PTB patients, but frequent positive proportions of TBGL-IgG (46%) and -IgA (36%) in HAs were the cause of low specificities of TBGL-IgG (54%) and -IgA (64%); that of TBGL-IgG+IgA (75%) was the highest. Antibody titres were positively correlated in TBGL-IgG+IgA double-positive HAs (HA+, 7/28, P < 0.01), but not in HA- (P > 0.05). Serum IgG and IgA levels were not correlated with TBGL-IgG or -IgA levels (P > 0.05). KL-6 and leptin levels were normal and were not different between HA+ and HA-, indicating absence of active TB in HAs. CONCLUSION: Enhanced TBGL-IgG+IgA responses in HAs could indicate latent TB infection. Careful follow-up studies in HAs could clarify the significance of elevated TBGL antibodies as early disease markers.

Secondary bronchiolitis obliterans organising pneumonia in a patient with carbamazepine-induced hypogammaglobulinaemia.

Here we describe a case of a secondary bronchiolitis obliterans organizing pneumonia (BOOP), which was associated with repeated respiratory infections caused by carbamazepine (CBZ)- induced hypogammaglobulinaemia. A 49-year-old woman had been treated with CBZ (400 mg/day). Two and a half years later, she developed of dyspnea with productive cough and high-grade fever. Chest roentgenogram and computed tomography showed bilateral infiltrates in lower lung fields. Her laboratory findings revealed severe hypogammaglobulinaemia, suggesting that an immune system disorder caused pulmonary infection. Histological examination by trans-bronchial lung biopsy (TBLB) demonstrated that many foamed alveolar macrophages were obstructing the alveolar ducts and adjacent alveoli, suggesting BOOP. After cessation of CBZ, the hypogammaglobulinaemia and chest roentgenogram findings markedly improved. The present case suggests that CBZ may have some adverse effects on the immune system and cause frequent airway infections, and that secondary BOOP could be induced by repeated infections caused by CBZ-induced hypogammaglobulinaemia.

Method for efficient storage and transportation of sputum specimens for molecular testing of tuberculosis.

SETTING: The polymerase chain reaction (PCR) is a highly sensitive method for the detection of Mycobacterium tuberculosis and is available in most countries, though to a lesser extent in rural areas. OBJECTIVE: To amplify M. tuberculosis DNA sequences of sputum spotted on FTA cards and compare them with the results of microscopic examination among culture-positive samples. DESIGN: A total of 102 sputum specimens of TB patients in treatment were spotted on FTA cards and stored at room temperature until DNA analysis. We assessed the IS6110 region of M. tuberculosis. The efficacy of the PCR assay for the direct detection of M. tuberculosis was evaluated and compared with the results of cultures (Middlebrook 7H9 broth) and smears of fresh sputum specimens. RESULTS: We were able to detect 10 fg/microl of mycobacterial DNA even after 6 months in storage. The PCR sensitivity and specificity using the FTA card system were 82% and 96%, while microscopic examination showed 41% and 95%, respectively. CONCLUSION: The FTA card system for the storage of bacterial DNA from sputum samples should be considered for the molecular diagnosis of tuberculosis. Samples can easily be obtained from geographically isolated populations and shipped by mail for accurate molecular diagnosis.

Low antibody response against tuberculous glycolipid (TBGL) in elderly gastrectomised tuberculosis patients.

To evaluate differences in anti-tuberculous glycolipid (TBGL) antibody titers in patients who developed tuberculosis (TB) with and without gastrectomy, 11 gastrectomised patients who developed TB after surgery (GS-TB), 19 TB patients without any other complications (TB), 12 gastrectomised patients who did not develop TB after surgery (GS) and 27 healthy subjects (H) with normal findings on chest X-ray were evaluated, although there were no differences in the clinical findings at admission between the TB and GS-TB groups. The assay used here allowed us to find low anti-TBGL antibody titers in GS-TB patients.

[Spontaneous regression of thymoma; report of a case].

A 44-year-old woman was admitted to our hospital with chest pain. Chest roentgenograms and computed tomography (CT) scan revealed an anterior mediastinal tumor and bilateral pleural effusion. However, CT scan 3 days after magnetic resonance imaging (MRI) revealed regression of the tumor. Extended thymo-thymectomy was performed via median sternotomy. The tumor was in the right lobe of the thymus. Pathologically the tumor was diagnosed as a mixed type non-invasive thymoma, but some parts of the tumor cells were necrotic. This is the 10th case of spontaneous regression of thymoma reported in the Japanese literature.

[Radiofrequency ablation for metastatic lung tumor].

BACKGROUND: Radiofrequency ablation (RFA) is a thermal ablation technique which results in coagulative necrosis. Several preliminary studies have evaluated the efficacy of RFA for liver tumor and benign prostate disease, but few studies for lung tumor. We experienced RFA for a metastatic lung tumor and it was effective. CASE: A 61-year-old woman was admitted to our hospital with chest pain. Extended thymothymomectomy with lymph node dissection was performed after diagnosis of thymic carcinoid. After 14 months, multiple small lung nodules, which had been 5-10 mm in diameter, were appeared and resected. However, 23 months after the first operation and 14 months after the second operation, multiple small lung nodules were appeared again and RFA was performed for 1 tumor without any complications. We used RITA 500 PA (RITA Medical Systems, INC.) and quadruple-hook radiofrequency probe with electrodes. Under local anaesthesia and ultrasound guidance, the probe was inserted into the target tumor and the hooks were deployed. The tumor became smaller (35 mm to 25 mm in diameter) in 2 months. CONCLUSION: RFA is an effective and minimally invasive technique to destruct local tumors.

Rapid alveolar liquid removal by a novel convective mechanism.

Although alveoli clear liquid by active transport, the presence of surface-active material on the alveolar surface suggests that convective mechanisms for rapid liquid removal may exist. To determine such mechanisms, we held the isolated blood-perfused rat lung at a constant alveolar pressure (PA). Under videomicroscopy, we micropunctured a single alveolus to infuse saline or Ringer solution in approximately 10 adjacent alveoli. Infused alveoli were lost from view. However, as the infused liquid cleared, the alveoli reappeared and their diameters could be quantified. Hence the time-dependent determination of alveolar diameter provided a means for quantifying the time to complete liquid removal (C(t)) in single alveoli. All determinations were obtained at an PA of 5 cmH(2)O. C(t), which related inversely to alveolar diameter, averaged 4.5 s in alveoli with the fastest liquid removal. Injections of dye-stained liquid revealed that the liquid flowed from the injected alveoli to adjacent air-filled alveoli. Lung hyperinflations instituted by cycling PA between 5 and 15 cmH(2)O decreased C(t) by 50%. Chelation of intracellular Ca(2+) prolonged C(t) and abolished the inflation-induced enhancement of liquid removal. We conclude that when liquid is injected in a few alveoli, it rapidly flows to adjacent air-filled alveoli. The removal mechanisms are dependent on alveolar size, inflation, and intracellular Ca(2+). We speculate that removal of liquid from the alveolar surface is determined by the curvature and surface-active properties of the air-liquid interface.

[Recurrence and pulmonary metastasis of extradural paraganglioma in thoracic vertebral canal: report of a case].

A 70-year-old female was operated on for extradural spinal cord tumor in 1982. Microscopic examination revealed the tumor as paraganglioma. Tumor recurred at paravertebral twice in 1985 and 1989, and they were also resected. In 1995, her chest X-ray film showed round tumor in the right upper field. Exploratory open lung biopsy was performed in 1996, and right upper lobectomy was performed according to for malignant lung tumor because intra-operative microscopic findings showed carcinoid or lung metastasis of paraganglioma. Chest wall tumor at paravertebral was resected at the same time. Postoperative microscopic examination revealed the tumors were same as operated paraganglioma. The 2nd thoracotomy was done in 1999, and two chest wall tumors and a pulmonary nodule in right S8 segment were resected. They were recurrence and pulmonary metastasis of paraganglioma. Now 18 years after initial operation, she is out of hospital in tumor free.

[Features of home care for patients with advanced breast cancer].

We examined the features of home care for patients with noncurable breast cancer. The patients were 21 women with advanced breast cancer who entered the home care program between April 1987 and May 2001. The first feature was that their young age: six of them were in their forties, five were in their fifties, and the mean age was 57.4 years old. The second feature was that the period home care was provided was long. The mean duration of home care from the beginning to their death was 143 days. This was because the period of sickness and the period until the breast cancer's relapsing were both long. The mean period until the relapse was 2.3 years, and the mean period of sickness was 4.1 years. The third feature was the great variety of symptoms. It is this cause that there are a lot of metastasis organs. The fourth feature was that no special treatment, such as infusion therapy, was really necessary to alleviate the symptoms. Pain control was important because there were a lot of patients whose main complaint was pain. However, pain could be controlled with morphine. In conclusion, if it is excluded not to have the nursing power because the age is generally young, home care can be comparatively offered to the person who has an advanced breast cancer for a long term.

[A patient with multiple pulmonary metastases from colonic cancer who survived for 5 years by effectual administration of 5'-DFUR].

The patient was a 69-year-old woman who had been diagnosed with a bowel obstruction due to colonic cancer, with simultaneous multiple pulmonary metastases. The primary lesion was resected and 5'-DFUR was administered for 2 years at an out-patient clinic. During those 2 years, there was no change in CEA value and the pulmonary lesions were fading on the roentogenograms. It then became doubtful whether the pulmonary shadows were real metastases or not, and 5'-DFUR administration was discontinued. After stopping the medication, her CEA value rose and the tumor shadows increased in intensity. 5'-DFUR was therefore re-administrated and her CEA value declined. Afterwards, a re-elevation in CEA value was seen, and low-dose FP therapy was added on an out-patient basis. Anti-cancer chemotherapy of 5'-DFUR (oral) and low-dose FP (i.v.) was contributed to her 5-year survival.

[Ca(2+)](i) oscillations regulate type II cell exocytosis in the pulmonary alveolus.

Pulmonary surfactant, a critical determinant of alveolar stability, is secreted by alveolar type II cells by exocytosis of lamellar bodies (LBs). To determine exocytosis mechanisms in situ, we imaged single alveolar cells from the isolated blood-perfused rat lung. We quantified cytosolic Ca(2+) concentration ([Ca(2+)](i)) by the fura 2 method and LB exocytosis as the loss of cell fluorescence of LysoTracker Green. We identified alveolar cell type by immunofluorescence in situ. A 15-s lung expansion induced synchronous [Ca(2+)](i) oscillations in all alveolar cells and LB exocytosis in type II cells. The exocytosis rate correlated with the frequency of [Ca(2+)](i) oscillations. Fluorescence of the lipidophilic dye FM1-43 indicated multiple exocytosis sites per cell. Intracellular Ca(2+) chelation and gap junctional inhibition each blocked [Ca(2+)](i) oscillations and exocytosis in type II cells. We demonstrated the feasibility of real-time quantifications in alveolar cells in situ. We conclude that in lung expansion, type II cell exocytosis is modulated by the frequency of intercellularly communicated [Ca(2+)](i) oscillations that are likely to be initiated in type I cells. Thus during lung inflation, type I cells may act as alveolar mechanotransducers that regulate type II cell secretion.

[Home anti-cancer therapy with a venous port].

Home anti-cancer chemotherapy and palliation in the terminal stage were performed for patients with advanced cancer of the digestive system, using a venous port implanted beneath the skin via the subclavian vein. Patients under 75 years of age (5 with esophageal, 61 gastric, 59 colorectal, 5 cholangio, 5 pancreatic, 1 hepatic and 1 ileal cancer) were treated. With two portable balloon pumps, continuous intravenous infusion of 5-FU (300 or 400 mg/body/day) combined low-dose injection of cisplatin (5 mg/body/day) was continued for 10 days, and repeated 3 times for 6 weeks. The response rate was 17.9% in 78 patients according to valuation of the tumor mass. In 119 patients also undergoing a tumor marker evaluation, an effect was seen in 26.1%. No severe side effects such as renal dysfunction or bone marrow suppression were seen, and no special infusion was needed. Therefore, such treatment can be continued for a long time. Use of a venous port should make easy the switchover to HPN and the amelioration of the symptoms of the terminal stage, such as pain, and helps patients cope with the worry. Therefore, the present technique is useful in a series of cancer treatments including surgery, chemotherapy and the amelioration of symptoms.

[Medical support system to enable advanced cancer patients to die at home].

Among 207 advanced cancer patients that received home care during the period from April, 1987 to December, 1998, 144 died in their own house, and 129 people were confirmed dead by a doctor of this department. Eighty (62%) of these 129 people died outside the hospital working hours. Moreover, 47 people (36%) died on a day the hospital was closed. The time difference between the actual death time and the doctor's death confirmation time was less than 60 minutes for 88 people, over 60 minutes for 41 people, over 120 minutes for 17 people, and over 180 minutes for seven people. The doctor in charge performed the death confirmation for 107 people (83%). Forty-seven people had received a visit by the doctor or nurse on the day of death, and 57 people had received a visit on the day before death. The existence of the medical support system of 24 hour correspondence and various guidance for the family on the method of making urgent reports when near death, how to spend the last hours, and the postmortem procedures were especially important in making home death possible.

[Home anti-cancer chemotherapy with continuous infusion of 5-FU combined with low-dose cisplatin injection via implantable venous port with portable balloon pump].

Home anti-cancer chemotherapy was performed for patients with advanced cancer of the digestive plantable venous port placed beneath the skin via the subclavian vein. 128 patients under 75 years old (enrolled: 6 patients with esophageal, 65 with gastric, 44 with colorectal, 5 with cholangio, 5 with pancreatic, one with hepatic and one with ileal cancer) were treated. Continuous intravenous infusion of 5-FU (300-400 mg/body/day) combined with low-dose injection of cisplatin (5 mg/body/day) was continued for 10 days, and repeated 3 times for 6 weeks. The response rate was 23.6% in 72 patients with valuation of tumor mass. In 83 patients for whom a tumor marker evaluation was also performed, an effect was seen in 30.1%. No severe side effects such as renal dysfunction were observed, and no special infusions were needed. Therefore, a quality of life was maintained in which bathing was possible and patients were released from the hospital. Hyperalimentation through the venous port, and palliation during the terminal stage, is easily accomplished. It is useful method for surgery, chemotherapy and palliative therapy in the treatment of cancer.

[Increase in pulmonary vascular permeability caused by increased adhesiveness of polymorphonuclear leukocytes and superoxide].

We report that mechanical stimulation of human neutrophils results in their accumulation in isolated rat lungs and in an increase in pulmonary vascular permeability. To determine whether reactive oxygen species were involved in this increase and, if so, whether it is mediate by xanthine oxidase metabolites, we assessed the effect of stimulated and unstimulated neutrophils, and of a superoxide scavenger, superoxide dismutase (SOD), and a xanthine oxidase inhibitor, allopurinol (ALLO) on pulmonary vascular permeability in isolated perfused lungs from Sprague-Dawley rats. Pulmonary vascular permeability in isolated rat lungs was assessed using a filtration coefficient determined by gravimetry. To quantify neutrophil accumulation in the lung, we measured myeloperoxydase (MPO). Neutrophils were stimulated by gentle agitation in a glass container for 10 s and Mac-1 was subsequently upregulated on the surface of the neutrophils. In lungs that received stimulated neutrophils, the pulmonary vascular filtration coefficient was about 5 times higher than in lungs that received unstimulated neutrophils. An increase in filtration coefficient was almost completely blocked by pretreatment with SOD or ALLO. However, the accumulation of stimulated neutrophils was not, or only partly, blocked by SOD or ALLO, respectively. We conclude that the increase in pulmonary vascular permeability caused by mechanically stimulated neutrophils was partly mediated by reactive oxygen species generated via the xanthine oxidase system.

[Home care for terminally ill cancer patients in 1997].

In 1997, home care was provided for thirty-seven terminally ill cancer patients, fifteen patients with gastric cancer, nine patients with colorectal cancer, four patients with breast cancer, and nine patients with other miscellaneous cancer. The shortest period of home care was three days, the longest was six hundred seventeen days, and the average was one hundred eight days. Medical treatment at home consisted of dosage of morphine for 30 patients, parenteral nutrition for 30 patients, dosage of steroids for 29 patients, infusion of haloperidol for 8 patients, continuous draining of ascites for 6 patients, and continuous draining of intestinal fluid through nasogastric tube for 3 patients. As of May 31, 1998, 3 patients were alive but 34 patients had died, 31 of them at home. The characteristic trends in this year were reinforcement of the home care system in our hospital, prolongation of mean at-home days, inhalation of nebulized morphine for management of dyspnea, restriction of indication of home infusion therapy and active cooperation with public health center and welfare office.