Correlation of susceptibility of Cryptococcus neoformans to amphotericin B with clinical outcome.

Testing of Cryptococcus neoformans for susceptibility to antifungal drugs by standard microtiter methods has not been shown to correlate with clinical outcomes. This report describes a modified quantitative broth macrodilution susceptibility method showing a correlation with both the patient's quantitative biological response in the cerebrospinal fluid (CSF) and the survival of 85 patients treated with amphotericin B (AMB). The Spearman rank correlation between the quantitative in vitro measure of susceptibility and the quantitative measure of the number of organisms in the patient's CSF was 0.37 (P < 0.01; 95% confidence interval [95% CI], 0.20, 0.60) for the first susceptibility test replicate and 0.46 (P < 0.001; 95% CI, 0.21, 0.62) for the second susceptibility test replicate. The median in vitro estimated response (defined as the fungal burden after AMB treatment) at 1.5 mg/liter AMB for patients alive at day 14 was 5 CFU (95% CI, 3, 8), compared to 57 CFU (95% CI, 4, 832) for those who died before day 14. These exploratory results suggest that patients whose isolates show a quantitative in vitro susceptibility response below 10 CFU/ml were more likely to survive beyond day 14.

Surgery for control of recurrent life-threatening ventricular tachyarrhythmias within 2 months of myocardial infarction.

Twenty-seven patients (mean age 57 +/- 7 years) underwent surgery for control of recurrent drug-refractory ventricular tachyarrhythmias (uniform ventricular tachycardia alone in 9 patients, ventricular tachycardia and ventricular fibrillation in 15 and ventricular fibrillation alone in 3) within 2 months of acute myocardial infarction. The mean number of major arrhythmic episodes per patient was 15 (range 2 to 200) and of drug failures 4 +/- 2. Left ventricular function was severely impaired in the majority (ejection fraction 29%; range 14% to 47%) and 18 patients (66%) had a left ventricular aneurysm. Endocardial resection guided by a combination of endocardial activation mapping during tachycardia and fragmentation mapping during sinus rhythm was performed in all patients. All electrically abnormal left ventricular endocardium was excised. Eight patients (29.6%) died within 30 days of surgery. Death was not related to age, time of surgery after infarction, ventricular function, bypass time or type of arrhythmia. Patients requiring emergency surgery had a higher early postoperative mortality rate than did those undergoing planned surgery (43% versus 15%). During a follow-up period of 32 +/- 20 months, there have been no arrhythmic deaths and only three patients (16%) have required antiarrhythmic drug therapy. When required in the early weeks after infarction, surgery for ventricular arrhythmias offers a high cure rate at a risk related to the patient's preoperative arrhythmia frequency, which in turn relates to the risk of arrhythmic death.

Importance of lead selection in QT interval measurement.

The influence of lead selection on QT estimation in the 12-lead electrocardiogram was assessed in 63 patients (21 control subjects, 21 with anterior myocardial infarction, 21 with inferior myocardial infarction). QT estimates varied between leads. The variation was greater in patients with myocardial infarction than in control subjects (mean dispersion of QT: control subjects, 48 +/- 18 ms [+/- standard deviation]; anterior myocardial infarction, 70 +/- 30 ms; inferior myocardial infarction, 73 +/-32 ms). The maximum QT in any lead (QTmax) was determined and the deviation of each lead from this maximum value calculated. In all 3 groups, anteroseptal leads (V2 or V3) provided the closest approximation to QTmax. Interlead variability was found to be mainly due to variation in timing of the end of the T wave, rather than the onset of the QRS complex. The variability due to leads was considerably greater than the variability due to cycles, observers or measurement error. Implementation of a variety of current lead selection practices resulted in widely divergent estimates of QT interval. It is concluded that there is a need for standardization of lead selection practice for QT measurement. If measurements are confined to one or a few leads, anteroseptal leads provide the closest approximation to QTmax.

Restriction fragment length polymorphism study of Mycobacterium tuberculosis in Thailand using IS6110 as probe.

SETTING: Three referral hospitals in central Thailand. OBJECTIVE: To determine the population structure of Mycobacterium tuberculosis isolated from the referral hospitals. DESIGN: Study of 211 isolates of the bacteria received from the hospitals in central Thailand by Southern hybridization, with IS6110 probe and other probes when indicated. RESULTS: In 43 isolates only one copy of IS6110 was observed. These could be further differentiated by DR- and PGRS-specific probes. Two large groups of isolates with similar hybridization patterns were identified. The Beijing family, comprising 80 isolates, was previously reported to be commonly found in China, Mongolia, Thailand and Korea. The Nonthaburi group, comprising 29 isolates, were local strains. The age, sex and HIV status of the patients did not significantly correlate with the chance of being infected by isolates of any particular hybridization pattern. However, clustered isolates were found more commonly among the members of both the Beijing family and the Nonthaburi group. CONCLUSION: Southern hybridization with IS6110 was found to be useful in studying the epidemiology of tuberculosis in Thailand. The existence of the Beijing family was confirmed. The unusually wide spread of the Beijing family in several countries in Asia merits further investigation.

Frequency of angina pectoris and coronary artery disease in severe isolated valvular aortic stenosis.

Angina pectoris is a frequent symptom of severe valvular aortic stenosis (AS), even in the presence of normal coronary arteries. To determine the prevalence of angiographically significant coronary artery disease (CAD) and its relation to angina pectoris and coronary risk factors in severe isolated valvular AS patients. All cases of symptomatic AS patients who underwent aortic valve replacement and preoperative cardiac catheterization at the Central Chest Hospital between January 1, 1986 and December 31, 1996 were retrospectively analyzed. Excluded were those with multiple valvular disease, aortic regurgitation of grade 2 or more, and prior coronary or valve surgery. A total of ninety consecutive patients with severe AS (64 men and 26 women, mean age 58.94 years, range 38 to 71) were studied. Significant CAD (coronary diameter stenoses > or = 50%) was found in 15 patients (16.7%). Typical angina was present in 66.7 per cent of them but it was also found in 46.7 per cent of the non-CAD patients. This symptom had low positive predictive value (22%). Of the patients without angina (n = 45) 11.1 per cent had significant CAD, The negative predictive value of angina alone was thus 89 per cent. By univariate logistic regression, the statistically significant variables to discriminate those with or without significant CAD were age, history of hypertension, positive familial history of premature CAD, and cholesterol level. However, only age and hypertension were statistically significant by multivariate logistic regression analysis. Coronary arteriography can probably be omitted in severe valvular AS, especially those without a history of hypertension and < 40 years of age in men and < 50 years in women. For all other cases, coronary arteriography is recommended. In our study, angina pectoris is not a significant predictor for associated CAD.

Transesophageal echocardiography during percutaneous mitral commissurotomy in patients with left atrial thrombus.

BACKGROUND: Transesophageal echocardiography (TEE) is used routinely before percutaneous transvenous mitral commissurotomy (PTMC) to detect left atrial appendage thrombus (LAAT) to avoid the risk of embolic complications. The issue of whether patients with small and fixed LAAT should be denied the potential benefit of PTMC is worth examining. OBJECTIVE: To evaluate the safety and efficacy of PTMC with Inoue balloon catheter in mitral stenosis patients with LAAT using TEE continuous monitoring during the procedure. MATERIAL AND METHOD: All TEE studies performed during PTMC and transthoracic echo-cardiography (TTE) performed the same day and repeated on the day after the procedure between March 1995 and January 2000 were reviewed. RESULTS: A total of 1,238 consecutive TEE during PTMC were reviewed. LAAT was detected in 111 patients (mean age 43.7 +/- 10.1 years, male:female = 1:2, atrial fibrillation : sinus rhythm 2.47:1). LAAT were grossly oval with the largest measuring 3.5 x 2.8 centimeters. Mobile LAAT was detected in 3 patients (2.7%), one of whom developed a transient ischemic attack and another had an episode of stroke after PTMC. Mitral valve area (by 2D Echocardiography) pre PTMC was 0.8 +/- 0.2 cm2 and post-PTMC was 1.5 +/- 0.3 cm2. Most of our patients became fully ambulatory and could be discharged from the hospital the day after the procedure, except for two patients who developed severe mitral regurgitation and needed elective mitral valve surgery thereafter. CONCLUSION: PTMC with the Inoue-balloon catheter can be carefully and safely performed in patients with small, fixed LAAT under continuous TEE guidance with acceptable risk.

Recovery of Cryptococcus neoformans from the nasopharynx of AIDS patients.

Nasopharyngeal swabbings, obtained from AIDS patients, were plated onto Niger seed agar containing antibiotics Cryptococcus neoformans was isolated from 35 out of 84 patients (41.7%) diagnosed as primary cryptococcal cases before antifungal administration, and 8 out of 86 (9.3%) cryptococcosis patients on antifungal therapy. The fungus could not be isolated from any of 447 samples from 194 AIDS patients not diagnosed with cryptococcosis. These findings are novel in that the presence of C. neoformans in AIDS patients at this site has never been looked at previously.

Ciprofloxacin and loperamide in the treatment of bacillary dysentery.

OBJECTIVE: To compare the safety and efficacy of loperamide plus ciprofloxacin with those of ciprofloxacin alone in the treatment of bacillary dysentery. DESIGN: Double-blind, placebo-controlled, randomized clinical trial. SETTING: Hospital in Thailand. PARTICIPANTS: Eighty-eight adults with dysentery seeking medical care between November 1990 and February 1992. Patients who had received prior antibiotics or antimotility drugs were excluded. INTERVENTION: All 88 patients with dysentery were treated with ciprofloxacin, 500 mg twice daily for 3 days. Forty-two of these patients were randomly assigned to receive loperamide, a 4-mg initial dose followed by 2 mg after every loose stool (as many as eight caplets [16 mg] daily), and 46 were randomly assigned to receive placebo. MEASUREMENTS: Stools were collected daily until resolution of diarrhea and again after 10 days. The time to passage of the last unformed stool, number of unformed stools, and symptoms were recorded after treatment. RESULTS: Shigella or enteroinvasive Escherichia coli (53%), Vibrio parahaemolyticus (16%), and Salmonella (7%) were the most common bacterial enteric pathogens identified in 88 patients with dysentery. In patients infected with Shigella or enteroinvasive E. coli, the median duration of diarrhea was 19 hours (25th to 75th percentiles, 6 to 42 hours) for those receiving loperamide plus ciprofloxacin compared with 42 hours (21 to 46 hours) for those receiving ciprofloxacin alone (P = 0.028). The median number of diarrheal stools for those receiving ciprofloxacin and loperamide was 2.0 (1 to 5 stools) compared with 6.5 (2 to 9 stools) for those receiving ciprofloxacin alone (P = 0.016). None of the participants had a temperature greater than 38 degrees C after 24 hours of treatment. None of the patients was infected with the same bacterial enteric pathogen more than 1 day after receiving treatment. CONCLUSIONS: Loperamide decreases the number of unformed stools and shortens the duration of diarrhea in dysentery caused by Shigella in adults treated with ciprofloxacin.

Survival of AIDS patients in the emerging epidemic in Bangkok, Thailand.

Survival from the time of AIDS diagnosis to death was determined retrospectively among Thai patients (> or = 13 years old) who attended a public tertiary care infectious disease hospital in a suburb of Bangkok, Thailand, from February 1987 through February 1993. An AIDS diagnosis was based on the 1987 Centers for Disease Control (CDC) definition, except Penicillium marneffei infection was included as an AIDS-defining condition. Of 329 AIDS patients, 152 (46.2%) had died. The median age at diagnosis was 31.5 years (range, 18-74) 306 patients (93.0%) were males. Reported risk categories were heterosexual contact (55.2%), injecting drug use (IDU, 22.6%), male homosexual or bisexual contact (9.5%), and unidentified risk or other (12.7%). Median survival time (Kaplan-Meier) for all patients was 7.0 months; 1-year survival probability was 39.2% (95% confidence interval [CI] = 31.5-46.9%). Cox's proportional hazards model showed three factors associated with survival: age, reported risk category, and presenting diagnosis. Patients aged 26 to 35 years survived longer (median survival time, 10.6 months; relative hazard [RH] = 0.61, 95% CI = 0.44-0.85, referent: others), as did patients in sexual risk categories (median survival time, 7.3 months; RH = 0.59, 95% CI = 0.40-0.78, referent: IDU and other categories). A single presenting diagnosis of extrapulmonary tuberculosis was also associated with longer survival (median survival time, 19.9 months, RH = 0.55, 95% CI = 0.35-0.86, referent: other diagnoses). AIDS patients in the early phase of the epidemic in Bangkok have much shorter survival times than patients in developed countries, in part perhaps because they are often diagnosed late in the course of HIV infection. Increased attention should be given to the early diagnosis and treatment of these patients.

Epicardial repolarization mapping in man.

A simple method was developed for recording epicardial monophasic action potentials intraoperatively in man. Potentials were recorded rapidly and reliably from multiple epicardial sites using a hand-held probe. The feasibility of repolarization mapping was assessed in 30 patients. It was possible to record technically adequate signals from most left ventricular and posterior right ventricular sites (success rates 72% and 61%, respectively), but it was more difficult to achieve satisfactory recordings over the free wall of the right ventricle (success rate 36%). The onset of cardiopulmonary bypass resulted in a transient rise in action potential duration of approximately 30-40 ms in the first minutes of bypass. An approximate steady state was achieved thereafter. Reproducibility of the method was assessed by mapping a small number of sites repeatedly. The 95% confidence limits for an estimate of repolarization time, based on a single potential, were +/- 21 ms. With 4 probe applications at each site, the confidence limits of the estimated site mean were reduced to +/- 8 ms. Based on this approach, statistically significant differences between sites were demonstrated in 9 of 10 patients, confirming that the method is sensitive enough to provide information on regional differences in repolarization. Intraoperative epicardial repolarization mapping has been shown to be a practical possibility. The technique holds promise as a means of assessing the role of dispersion of repolarization in arrhythmogenesis in man.

Phenotypic switching and genetic diversity of Cryptococcus neoformans.

Niger seed agar was used as a primary plating medium for the isolation of Cryptococcus neoformans from cerebrospinal fluid specimens from AIDS patients with untreated primary cryptococcosis. The medium was used as the primary means to detect variations in the colony morphology of the yeast. To search for phenotypic and genetic variations, nine patients individually harboring two or three types of colony morphology were studied. Intraindividual isolates from nine patients had minor variations in the API 20C profile, and the MICs of one or more antifungal agents (amphotericin B, fluconazole, and itraconazole) for isolates from three patients were significantly different. Intraindividual isolates from three patients had minor karyotype differences, and one showed a dramatic chromosomal length polymorphism. In addition, three serial isolates from a patient with two episodes of infection showed similar karyotypes, confirming persistent infection by the same strain. Random amplified polymorphic DNA products were identical for all isolates (including three isolates from a relapse case). Our results provided evidence suggesting that (i) in humans, C. neoformans may undergo phenotypic and genetic changes during early infection prior to antifungal agent administration; (ii) dramatic variations in electrophoretic karyotypes and in phenotypes, as demonstrated during the early infection of one patient, may be due to infection by different strains; and (iii) the use of niger seed agar as a primary plating medium is useful for studying antifungal susceptibility, phenotypic switching, genetic diversity, and multiple-strain infections.

Sequence of epicardial repolarisation and configuration of the T wave.

Epicardial activation and repolarisation sequences were investigated in patients with upright or inverted T waves in left ventricular leads of the surface electrocardiogram. Fifteen patients were studied: 10 were undergoing coronary artery bypass grafting (upright T waves) and five aortic valve replacement (four patients with T inversion). Monophasic action potentials were recorded intraoperatively from eight to 10 left ventricular sites in each patient. In patients with upright T waves there was an inverse relation between the duration of the monophasic action potential and the activation time (mean slope -1.44). As a consequence, activation and repolarisation proceeded in opposite directions. Dispersion of repolarisation time (14 ms) was less than dispersion of activation time (23 ms). In patients with T wave inversion caused by aortic stenosis there was no relation between the duration of action potential and activation time; the repolarisation sequence resembled the activation sequence, and the dispersion of repolarisation time was greater than the dispersion of activation time (31 and 26 ms respectively). These results show that there are epicardial repolarisation gradients in man and that these are related to the configuration of the T wave. In patients with upright T waves an inverse relation between the duration of the action potential and the activation time reduces the dispersion of the repolarisation time. When the T wave was inverted this relation was no longer found and the dispersion of repolarisation increased.

Unrecognised Mycobacterium tuberculosis bacteraemia among hospital inpatients in less developed countries.

BACKGROUND: Nosocomial transmission of Mycobacterium tuberculosis is a global public-health concern. Although early clinical recognition of M. tuberculosis in hospital inpatients is critical for effective infection control, such recognition may be difficult in patients with HIV infection. To find out whether M. tuberculosis bacteraemia frequently goes unrecognised, we did a prospective blood-culture survey in an infectious-diseases hospital in Thailand and a general hospital in Malawi. METHODS: Consecutive febrile (> or = 37.5 degrees C axillary or > or = 38.0 degrees C orally) hospital inpatients (aged > or = 18 years) were enrolled; blood was obtained for mycobacterial culture and HIV testing. Simple diagnostic tests, such as chest radiographs and sputum smears, were ordered by clinicians as deemed necessary, and were carried out with existing local resources. FINDINGS: Of 344 patients enrolled, 255 (74%) were HIV infected, the median age was 33 years (range 18-87), and 208 (61%) were male. 34 (10%) patients had M. tuberculosis bacteraemia; five of these patients were already on antituberculosis therapy. Only HIV-infected patients had M. tuberculosis bacteraemia. Of the 29 patients with M. tuberculosis bacteraemia who were not already receiving antituberculosis therapy, 13 (45%) had an abnormal chest radiograph or a positive sputum smear. 16 (55%) patients had no additional diagnostic test results to indicate M. tuberculosis infection; 18 (81%) of these had a cough. INTERPRETATION: In less developed countries where both M. tuberculosis and HIV infections are prevalent, M. tuberculosis bacteraemia may frequently go unrecognised among febrile hospital inpatients.

PIP: A blood-culture survey was conducted in Thailand and Malawi to measure the prevalence of Mycobacterium tuberculosis bacteremia among adult inpatients. A total of 344 febrile patients, aged 18 years or older, were recruited. Blood samples were taken for mycobacterial culture and HIV testing. Simple diagnostic tests, such as chest radiographs and sputum smears, were also carried out. Findings revealed that 255 (74%) patients were infected with HIV, and 34 (10%) patients had M. tuberculosis bacteremia. All patients who had M. tuberculosis bacteria were HIV-infected. Out of the 29 patients with M. tuberculosis bacteria who were not receiving antituberculosis therapy, 13 (45%) had an abnormal chest radiograph or a positive sputum smear; 16 (55%) patients did not manifest M. tuberculosis infection in their test results and were defined to have an unrecognized active disease. Moreover, oral thrush, chronic cough, fever or weight loss remained significantly associated with tuberculosis bacteremia. The findings suggest that tuberculosis-control efforts should also include the improvement of availability and use of chest radiographs and sputum smears to diagnose active disease, especially in developing countries where it is most needed.

Fever and human immunodeficiency virus infection as sentinels for emerging mycobacterial and fungal bloodstream infections in hospitalized patients >/=15 years old, Bangkok.

To determine the etiology of bloodstream infections (BSIs) in hospitalized patients >/=15 years old in Thailand, prospectively enrolled, consecutive febrile (>/=38 degrees C) patients were admitted to one hospital during February-April 1997. After a patient history was taken and a physical examination was performed, blood was obtained for comprehensive culture and human immunodeficiency virus (HIV) testing. Of 246 study patients, 119 (48%) had BSIs, and 182 (74%) were infected with HIV. The 2 most common pathogens were Cryptococcus neoformans and Mycobacterium tuberculosis (30 and 27 patients, respectively). HIV-positive patients were more likely than HIV-negative patients to have mycobacteremia (57/182 vs. 0/64, P<. 0001), fungemia (38/182 vs. 2/64, P<.001), or polymicrobial BSIs (19/182 vs. 0/64, P<.002). Clinical predictors of BSIs included HIV infection, chronic diarrhea, lymphadenopathy, or splenomegaly. Mortality was higher among patients with than those without BSIs (P<. 001). Cohort-based microbiologic studies are critically important to diagnose emerging pathogens and to develop algorithms for empirical treatment of BSIs in developing countries.