Interferon gamma for diagnosing tuberculous pleural effusions.

BACKGROUND: A study was undertaken to evaluate the diagnostic value of pleural fluid concentrations of interferon gamma (IFN-gamma) as a marker of tuberculosis. METHODS: Patients admitted to King Chulalongkorn Memorial Hospital between April 1997 and January 1998 with a lymphocytic exudative pleural effusion were enrolled into the study. The pleural fluids were examined for cytology, staining for acid fast bacilli, and mycobacterial culture. Pathological examination and mycobacterial culture were performed on each pleural biopsy specimen. The diagnosis of tuberculosis was made when one of the following criteria was met: (1) Mycobacterium tuberculosis was isolated from either the pleural fluid or pleural tissue; (2) granulomas were demonstrated in the pleural tissue which stained positive for acid fast bacilli (AFB); or (3) in the presence of granulomas negative on staining for AFB in pleural tissue there was a response to antituberculous treatment on follow up. All pleural fluid samples were stored at -70 degrees C and the IFN-gamma level was measured by immunoassay. Analysis was made using sensitivity, specificity, and likelihood ratio for a positive test result. The best cut off point was determined by the highest likelihood ratio and receiver operating characteristic curve. RESULTS: A total of 66 patients were enrolled and tuberculosis was confirmed in 39 of them. The diagnoses in the non-tuberculous group included malignancy (15), paramalignancy (11), and chronic pleuritis secondary to infective endocarditis (1). The mean (SE) IFN-gamma level in the pleural fluid was significantly higher in the tuberculous group than in the non-tuberculous group (1493.3 (131.3) pg/ml versus 80.1 (50.4) pg/ml, p<0.001). The overlap between the two groups was minimal. At the cut off value of 240 pg/ml the sensitivity was 94.9% (95% CI 86.6 to 100), the specificity was 96.3% (95% CI 89.2 to 100), and the likelihood ratio for a positive test result was 25.6. CONCLUSIONS: The pleural fluid concentration of IFN-gamma is a good and useful diagnostic marker of tuberculosis presenting as a lymphocytic exudative pleural effusion.

The role of the methacholine inhalation challenge in adult patients presenting with chronic cough.

One hundred and twenty two patients who were presenting with chronic persistent cough for more than 3-4 weeks were studied. Using anatomical and stepwise approach, we could identify the cause of chronic cough in 96% of the patients. The most common causes were due to postnasal drip syndrome (PND) (45%) and bronchial asthma (26%). We also demonstrated the important role of methacholine inhalation challenge in the diagnostic work up. The procedure could identify the patients who had bronchial hyperresponsiveness (BHR) in 52% of the cases. The severity degree of the BHR was classified into three levels. Mild or nonspecific BHR was defined as PC20 16-25 mg/ml. This could be found in many diseases such as PND and bronchiectasis. Moderate degree of BHR (PC20 8-16 mg/ml) was found in patients with PND and asthma. PC20 of less than 8 mg/ml was considered to be the most severe degree and it seemed to be specific for the diagnosis of asthma (positive predictive value 100%). Other condition that caused chronic cough were drug-induced, especially angiotensin-converting enzyme inhibitors, gastroesophageal reflux disease (GERD), idiopathic pulmonary fibrosis, subgottic cancer and idiopathic cough. These conditions may require invasive diagnostic work up, such as fiberoptic bronchoscopy and tissue biopsy. The treatment of chronic cough was according to the etiology. Thus, the patients presenting with chronic cough should be investigated to identify the cause, and it was not just only the administration of cough suppressant drugs in these patients.

Management of thai cobra bites with a single bolus of antivenin.

Between January 1981 and December 1991, 68 adults were treated at Chulalongkorn University for cobra bites. Respiratory failure developed in the bite victims even when an adequate genus-specific antivenin was administered at the onset of neuromuscular paralysis. The duration of time spent on a respirator was, however, significantly less in patients treated with an intravenous 100-ml antivenin bolus given at the onset of neurotoxic signs. We found that a bolus of 100 ml of purified equine antivenin produced by the Queen Saovabha Memorial Institute, Bangkok, from Naja kauthia venom was adequate and that increasing the dose did not lead to added benefits. Time spent on a respirator was approximately 10 h in antivenin-treated groups and 40 h if no antivenin or an inadequate dose was used. Competent respiratory and nursing care alone without antivenin will lead to eventual recovery and prevent death. Local bite site tissue necrosis and duration of hospitalization were not related to the dose of antivenin given. Hospitalization was prolonged in subjects who developed sepsis or who had severe tissue necrosis or other surgical or medical complications.

Spontaneous recovery from severe neurotoxic envenoming by a Malayan krait Bungarus candidus (Linnaeus) in Thailand.

A patient bitten by Bungarus candidus (Malayan krait) developed nausea, vomiting, weakness, and myalgia 30 minutes after being bitten. One hour later, ptosis and occulomotor palsies as well as tightness of his chest were noted. Respiratory failure requiring mechanical respiration appeared 8 hours after the bite and lasted for nearly 96 hours. The two bite sites were virtually painless and resulted in slight transient erythema and edema. No specific antivenin was available, and treatment consisted of respiratory support and management of aspiration pneumonitis. Recovery was complete.

Effect of inhaled corticosteroids on bronchial hyperresponsiveness in patients with mild asthma.

We studied the effect of inhaled budesonide on bronchial hyperresponsiveness (BHR) in twenty mild asthmatic patients. The study was conducted as a randomized, double-blind, placebo-controlled study. Before entering the study, the patients performed methacholine inhalation challenge (MIC) using a reservoir method to assess BHR. Then, they were randomly allocated to receive budesonide turbuhaler (200 micrograms/dose) or placebo turbuhaler two inhalations, twice daily for eight weeks. During the study, each patient recorded daily asthma score and daily number of puffs of beta 2 agonist and they were assessed at weeks 4 and 8. At the end of the treatment, MIC was repeated again. Patients receiving budesonide showed a significant improvement in airway responsiveness compared with those receiving placebo (p < 0.05). They also showed a significant improvement in asthma severity score and a significant decrease in beta 2 agonist bronchodilator use. This study also suggested that inhaled corticosteroids may be the primary treatment in patients, even with mild asthmatic and well-controlled symptoms.

Prognostic factors in patients hospitalized with pneumonia.

Prognostic factors in patients hospitalized with pneumonia was analysed from 526 non-immunocompromised host patients who were admitted to the Medical Department of Chulalongkorn Hospital during the period of January 1987 to December 1991. The overall mortality was 30.5 per cent. The causes of death were 12.7 per cent of progressive or uncontrolled pneumonia, 10.1 per cent of underlying diseases and 7.2 per cent of complications of assisted ventilation. Patients aged 60 or older than 60 years, abnormal host, mental status changes, respiratory failure, shock, bronchopneumonia, g-ve pneumonia had significantly higher mortality than those who had no such conditions. Patients with pneumonia who had respiratory failure and shock had highest mortality at 70.2 and 85.1 per cent, respectively. Our study indicated that the presence of pleuritic chest pain and pleural effusion had a favourable effect on the outcome.

Pneumonia with pleural effusions.

One hundred and forty three among five hundred and twenty-six cases of bacterial pneumonia in adults (27.2%) who had pleural effusion (parapneumonic effusion) admitted to Chulalongkorn Hospital during the period January 1987 to December 1991 were analyzed. There were 40 cases with effusion that was less than 10 mm thick on chest decubitus film, 44 cases of uncomplicated exudative phase, 40 cases of complicated exudative phase (early empyema) and 19 cases of empyema. Most patients in our study required thoracocentesis (72%), had early empyema and emyema (41.3%) as well as high incidence of positive organisms on Gram stain in pleural fluid. This indicates that our patients may have had a prolonged clinical course before coming to the hospital. About half of our patients had pleuitic chest pain or signs of pleural effusion. Among the various stages of parapneumonic effusion, the empyema group had the most delayed response to treatment and needed intercostal drainage for twice the duration of the early empyema group (15.69 vs 7.55 days). The overall mortality was 22.4 per cent. Factors associated with death were advanced age, hospital acquired and broncho-pneumonia, abnormal host, no pleuritic chest pain, no signs of consolidation, respiratory failure, shock and complications of assisted ventilation.

Bacterial pneumonia in the elderly.

Five hundred and twenty-six cases of bacterial pneumonia in adults admitted to Chulalongkorn Hospital during the period January 1987 to December 1991 were studied, comparing the elderly aged > or = 60 years (241 cases) with the nonelderly < 60 years of age (285 cases). The study indicates that there was a significantly increased number of community and hospital-acquired pneumonia in the elderly than previously reported. Pneumonia in the elderly might present with no fever, no cough no signs of parenchymal infiltration, but significant mental changes. There was a higher incidence of pleural involvement, but lower incidence of septic shock in the non-elderly than the elderly, which suggests that the nonelderly had better systemic resistance against bacterial infection than the elderly. There was no significant difference in complete blood count between the two groups. However, sputum specimens to be collected through endotracheal tube and Gram-negative bacilli on Gram stain were found more in the elderly than the non-elderly. The elderly had more respiratory failure requiring mechanical ventilation, septic shock, and had higher mortality than the non-elderly. They also required longer duration of treatment and hospitalization. There were parameters which indicated the high-risk factors for mortality among the elderly. These included hospital-acquired pneumonia, bronchopneumonia, Gram-negative pneumonia, abnormal status of host, sputum specimens requiring collection by suction, respiratory failure and septic shock.

Management of cobra bite by artificial respiration and supportive therapy.

During the period when the hospital ran out of cobra antivenom, 4 patients bitten by cobra with neuromuscular symptoms and respiratory depression were treated with artificial respiration. Complete recovery was noted within 36 to 72 hours. The data are interpreted to indicate the reversible binding of the venom to receptors. Artificial ventilation appears to be another alternative to specific antivenom treatment and may be used when the antivenom is not available or if there is antivenom hypersensitivity.

Community- and hospital-acquired pneumonia in medical intensive care unit.

Seventy-four cases of pneumonia admitted to the Medical Intensive Care Unit of Chulalongkorn Hospital from January 1986 to December 1988 were analyzed. There were 52 males and 22 females with 46, 26 and 2 cases of community-, hospital- and combined-acquired pneumonia, respectively; the average age on admission was 58 +/- 18.1 years. The majority of the patients had abnormal host or underlying pulmonary diseases. Most of the cases with community-acquired pneumonia were admitted to the ICU because of respiratory failure (85%) and most of the cases with hospital-acquired pneumonia had ventilator-associated pneumonia (71.4%). The dominating pathogens in community- and hospital-acquired pneumonia were Gram-positive and Gram-negative organisms, respectively. There were no significant differences in initial clinical manifestations, laboratory data, complications, between the two groups. However, the duration on antibiotic, respirator, leukocytosis and stay in hospital were significantly longer in hospital acquired than community acquired pneumonias. Overall mortality was 63.5 per cent, the causes of which were progressive or uncontrolled pneumonia and mechanical ventilation complications in 37.8 and 25.7 per cent of the cases, respectively. High-risk factors of the non-surviving groups included pneumonia on assisted ventilation, mechanical ventilation complications, shock and the presence of Gram-negative bacilli. Our study indicates that the patients required assisted ventilation because of the severity of the underlying pulmonary conditions rather than the extent of the pneumonia itself. Gram-negative pneumonia predisposed the patients requiring mechanical ventilation to develop complications. The duration on mechanical ventilation, ICU admission and hospitalization were 13.84, 13.21 and 29.08 days, respectively.

Mechanical and non-mechanical ventilation of respiratory failure in chronic obstructive pulmonary disease.

Among 182 episodes with ARF (PaCO2 > 50 torr) in 400 episodes of COPD patients who were admitted to Chulalongkorn Hospital during the period 1982 to 1986, despite conservative treatment, 66 developed severe acute respiratory failure requiring assisted ventilation. Patients with a history of chronic cough, pneumonia as a precipitating factor and more severe ARF on admission, as indicated by palpitation, headache, cyanosis, alteration of consciousness, cor-pulmonale and decompensated acidosis (pH < 7.30), were likely to require mechanical ventilation. Indications for mechanical ventilation were carbon dioxide narcosis (43 episodes), severe hypoxemia despite on a high FIO2 (one episode), various combination parameters of respiratory muscle fatigue, cardiovascular instability (22 episodes). The major complications of mechanical ventilation were pneumonia, sepsis, pneumothorax, UGI bleeding of 16, 8, 5 and 9 episodes, respectively. The average duration of assisted ventilation and hospitalization were 15.8 and 19.02 days, respectively. The mortality rate was 50 per cent in the mechanical ventilation group compared with 9.8 per cent in the non-mechanical ventilation group. Increased mortality rate was found in those with pneumonia as the precipitating factor (68.4 vs 14.3%, respectively, in comparing the two groups). Complications of mechanical ventilation, which included pneumonia, sepsis, fluid overload, hyponatremia and persistent acidosis, were high-risk factors for the non-surviving group.

Spontaneous pneumothorax in chronic obstructive pulmonary disease.

There were 34 episodes of pneumothorax out of 400 episodes of COPD (i.e. 8.5% of the total) among patients who were admitted to Chulalongkorn Hospital during the period 1982 to 1986; the episodes of pneumothorax occurred among 22 males and one female, with the average age on admission being 64.0 +/- 8.5 years. All patients had a long history of smoking (average 40 years) with a history of recurrent pneumothorax (47.8%) and two episodes of pneumothorax per patient. Since only about one third of our patients had chest pain or positive signs of pneumothorax on physical examination, the possibility of pneumothorax should be considered in every patient who develops sudden and increasing shortness of breath, especially during mechanical ventilation, or even in association with other obvious precipitating factors, e.g. URI. With regard to complications, there were eight, four, two, two and five episodes of severe respiratory failure requiring assisted ventilation, tension pneumothorax, bilateral simultaneous pneumothorax, pneumomediastinum with subcutaneous emphysema, and plural effusion, respectively. The death rate was 23.5 per cent. Patients who had a pneumothorax requiring assisted ventilation or who developed a pneumothorax during assisted ventilation had a grave prognosis because of multiple complications from mechanical ventilation. Two episodes with minimal pneumothoraxes achieved re-expansion after conservative treatment. The treatment required 3.3 days for the lung to fully expand, 9.6 days when the air-leak stopped and the duration of tube drainage was 10.8 days. Our study indicates that the longer the duration of lung collapse the longer the time required for re-expansion of the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic obstructive pulmonary disease at Chulalongkorn Hospital: an analysis of 400 episodes.

Four hundred episodes of COPD among patients admitted to Chulalongkorn Hospital between 1982 and 1986 were analyzed. There were 193 males and 45 females with 325 and 75 episodes of admission, respectively; the average age on admission was 68.4 +/- 0.5 years. The most significant associated underlying factor was cigarette smoking in 94 per cent of the cases, with the patients smoking an average of 1.15 packs of cigarettes per day for 43 years. In our study, 26.8 per cent of the patients had a cough, with the average age at onset being 47.4 +/- 2.1 years. The most common clinical manifestation was dyspnea with 58.5, 35.2 and 0.5 per cent having dyspnea functional class II, III, IV and with the average age at onset being 61.1 +/- 0.7, 66.6 +/- 0.7 and 71.0 +/- 1.0 years, respectively. An important manifestation on admission was dyspnea functional class III and IV, which were present in of 89 per cent of the cases. The main precipitating factors which led to the patients' admission were upper respiratory tract infection, pneumonia, bronchospasms and congestive heart failure, which accounted for 48.0, 10.0, 8.5, 31.8 and 18.3 per cent of the cases, respectively. With regard to these complications, there were 16.5, 48.3, 31.1 and 12.5 per cent of the patients who suffered respiratory failure requiring assisted ventilation, corpulmonale, polycythemia and peptic ulcer, respectively. Arterial blood gas on admission revealed a pH level of 7.36 +/- 0.1, pCO2 of 53.3 +/- 23.7 torr, and PO2 of 54.2 +/- 19.9 torr.(ABSTRACT TRUNCATED AT 250 WORDS)

Elucidation on acidity and low glucose concentration in parapneumonic effusion.

Studies were conducted on three consecutive patients with parapneumonic effusions by (a) serial analyses of plasma -pleural fluid glucose, pH, PCO2, and antimicrobial levels, and (b) serial analyses to determine the pH and PCO2 levels of pleural fluids that underwent in vitro incubation, before and after antimicrobial administration. The pleural fluid pharmacokinetics of the three antimicrobials followed a large reservoir model by increasing drug levels gradually, reaching the peak values at about two to seven hours following administration, while serial pleural fluid glucose levels showed a delayed rise or no rise in concentration, respectively. The molecular weights of the three antimicrobials are greater than that of the glucose, thus suggesting that over-utilization of glucose within the pleural cavity is more likely the cause of this situation than the transport defect. In the in vitro incubation study, the serial pleural fluid pH and PCO2 levels before antimicrobial administration progressively decreased, while those following the administration of antimicrobials were stable during the first few hours. The results indicate that, in cases of parapneumonic effusion, the inflamed pleurae and the infectious pleural fluid (empyema) over-utilizes pleural fluid glucose leading to increased fluid acidity.

Status asthmaticus: an analysis of 560 episodes and comparison between mechanical and non-mechanical ventilation groups.

An analysis and comparison of 286 adult patients involving 560 episodes of status asthmaticus admitted to the Medical Service of Chulalongkorn Hospital during the years 1984 through 1988 were examined. There were 58 patients who required mechanical ventilation 75 times compared with 228 patients with 485 episodes of attack who did not require the use of mechanical ventilation. The increased risk factors for status asthmaticus among those who required assisted ventilation were as follows: younger age at onset of asthma, younger age of severe attack, chronic asthma (especially unstable asthma), previous history of intubation and mechanical ventilation, shorter duration of severe attack and extremely severe attack in the sitting position before arriving at the emergency room, receiving beta 2 adrenergic inhaler, mistakenly taking beta blockers, high fever (over 38 degrees C) as a result of respiratory tract infection, increased initial pulse rate (over 125 beats/minute) and white blood cell count of over 16,000/mm3, and pneumothorax on admission. Simple asthma and history of taking franol or tedral in status asthmaticus indicated a low risk for mechanical ventilation. The taking of glucocorticoids did not pose a risk to status asthmaticus requiring mechanical ventilation.

Relationships between pleural fluid pH, PCO2 to pleural fluid PO2, amylase, protein, glucose and white cells in tuberculous and malignant effusions.

The relationships between pleural fluid pH and PO2 to pleural fluid PO2, amylase, protein, glucose, white cell count were examined in 110 cases of tuberculous and 140 cases of malignant pleural effusions. Pleural fluid amylase concentrations of 200 or more units/ml indicated malignant effusions rather than tuberculous effusions with a specificity of 92.7 per cent and sensitivity of 27.1 per cent. There was evidence which suggested that the increasing pleural fluid amylase concentrations were due to the excessive leakage of serum amylase into the pleural cavity secondary to the break-down of capillaries by tuberculosis and malignancy as well as the production of amylase by tumor cells invading the pleura. The decreasing pleural fluid pH and increasing pleural fluid PCO2 had a significant linear relationship with decreasing fluid PO2, increasing pleural fluid protein and decreasing fluid glucose. These indicated a leakage of serum protein into the pleural cavity and the over-utilization of glucose relative to the transport defect of low pleural fluid glucose concentrations in the acidotic fluid of tuberculous and malignant effusions. No relationship between pleural fluid pH and PCO2 to pleural fluid and white cell count was found in the present study.

Mechanical ventilation in status asthmaticus: experience with 75 episodes.

Mechanical ventilation in 75 out of 560 status asthmaticus episodes during a five-year period (1984-1988) at Chulalongkorn Hospital were analyzed. There were 58 patients with an average age of onset of first asthmatic attack of 18.5 years and an average age when requiring mechanical ventilation of 33 years, which is significantly younger than among those who did not require assisted ventilation. At the time of intubation, four patients were in sudden unexpected arrest and 19 patients were urgently ventilated because of respiratory muscle fatigue or carbon dioxide narcosis; the remaining 52 patients required elective mechanical ventilation. The arterial blood gas of 52 patients revealed a pH of 7.11 +/- 0.66, PaCO2 of 58.0 +/- 5.5 mmHg, and HCO3 of 15.0 +/- 5.8 mEg/L. Controlled mechanical ventilation was maintained for a mean of 38.68 hours. Fifty-one patients required intravenous diazepam (average dose = 24.3 mg) and 37 required morphine (average dose = 11.1 mg) for good syncronization in controlling mechanical ventilation. Pneumothorax was the most common complication with four, nine and one episodes occurring prior to, during and after assisted ventilation, respectively. Four, one and two patients developed the complications of pneumonia, atelectasis of the left lung due to mucous plugging and upper gastrointestinal hemorrhage, respectively. There were six patients who died of complications: four of brain anoxia, one of pneumothorax and another of unexplained cause.

The pathogenesis of low pleural fluid glucose in acidotic malignant pleural effusions.

To clarify the pathogenesis of low glucose concentrations in acidotic pleural fluid of malignant effusion, simultaneous studies of 1) serial plasma-pleural fluid glucose, pH, PCO2, gentamicin, tobramycin and netilmicin in vivo, and 2) serial in vitro incubation of pleural fluid pH and PCO2 were conducted in 19 cases. In all effusion samples, the pleural fluid pH and PO2 levels were lower and the CO2 levels were higher than those of arterial blood, respectively. The pleural fluid aminoglycoside levels increased gradually, reaching the maximum values after about four to seven hours, thereafter, it gradually decreased. There were three types of serial pleural fluid-plasma glucose concentrations, of which types 2 and 3 showed either a delayed rise or no rise in pleural fluid glucose concentrations, respectively. Serial pleural fluid pH and PCO2 levels remained stable during the in vitro incubation study, especially during the first three hours. The pleural fluid kinetics of the three aminoglycosides followed a large reservoir model without any relationships to pleural fluid pH, PCO2, fluid-volume and no significant differences of the kinetics among the three aminoglycosides. This indicated that the diffusion block of the antibiotics did not depend on molecular weight nor pH, PCO2 dependent. Since the molecular weight of three aminoglycosides is greater than that of glucose, lactic acid, CO2 and O2, it may be concluded, therefore, that an over utilization of glucose and O2 with an over production of lactic acid and CO2 by the pleura, rather than glucose transport defect, results in a low glucose concentration in malignant effusions.

Emergency room assessment and adrenaline treatment of patients with acute asthma of different severity.

The adequacy of emergency room assessment and treatment of patients with acute severe asthmatic attacks was evaluated by analyzing the course of 451 visits of 348 patients to Chulalongkorn hospital's Emergency Room. Eighty-five per cent of the patients had an initial index score of greater than or equal to 4 and an average peak expiratory flow rate of 92.16 +/- 46.3 L/min. The discharge index score was 85 per cent with a score of less than or equal to 3 and an average peak expiratory flow rate of 192 +/- 40.3 L/min. Our study indicated that the predictive index proposed by Fischl et al correlated with the severity of airway obstruction; however, the initial index did not help with emergency room decision-making in predicting which patients might be hospitalized, have a relapse or be discharged. In fact, in our emergency room department, the index score to determine airway obstruction and the pattern of response to treatment were better predictors of the outcome, which was classified into three categories: non-responsive or minimally responsive, responsive, and partially responsive. By using conventional clinical criteria (i.e. recumbent position with elimination of laboured breathing, disappearance of dyspnea and reduction of wheezing), there was a 93 per cent accurate determination in the episodes of patients who responded sufficiently to the emergency room treatment to allow their discharge. The remaining 7 per cent of those seeking emergency treatment were hospitalized, which is a lower incidence than that of others series.(ABSTRACT TRUNCATED AT 250 WORDS)

Fiberoptic bronchoscopy in diagnosis of patients with suspected active pulmonary tuberculosis.

Patients suspected of having active pulmonary tuberculosis, in whom acid-fast bacilli (AFB) are not demonstrated on sputum direct smear, present a difficult diagnostic and therapeutic problem. Flexible fiberoptic bronchoscopy is a useful procedure in evaluating these patients. Within five years, during the period of January 1983 to December 1987, 112 patients who were suspected of having active pulmonary tuberculosis underwent fiberoptic bronchoscopy. The diagnosis of pulmonary tuberculosis was established by using this procedure in 76 per cent of cases. Immediate diagnosis were made from microscopic specimens obtained from bronchoscopy in 38 of 65 patients (58%). It is concluded that fiberoptic bronchoscopy should be performed in evaluating patients with negative smears for AFB who are clinically suspected of having tuberculosis before initiating a trial of antituberculous drugs. The technique is safe and markedly efficacious in making an immediate diagnosis and uncovering other diseases that present themselves like tuberculosis.