Multidrug-resistant tuberculosis. 4. Treatment and prognosis of multidrug-resistant tuberculosis

Mucinous gastric carcinoma is a rare pathologic subtype of gastric adenocarcinoma. Whether the mucin behaves aggressively as in mucinous colorectal carcinoma is still controversial. Most mucinous gastric carcinomas are diagnosed from surgical specimens. The mucinous gastric carcinoma in this case report was discovered preoperatively according to its characteristic presentation. An upper gastrointestinal endoscopic examination showed a round protruding tumor of greater than 4 cm in size on the mid-body of the stomach; it had an uneven, friable and shiny surface. The surface was coated with a sticky layer of mucin-like substance, which persisted even after the aspiration of the gastric juice. Endoscopic ultrasonography (EUS) revealed a large heterogeneous hyperechoic tumor mass, originating from the mucosal and submucosal layers, on the body of the stomach. The mass was covered with a thick layer of hypoechoic amorphous substance. Hence, a mucin-producing tumor was suspected. Subsequent surgical biopsy proved the mass to be a moderately differentiated mucinous adenocarcinoma. This case illustrates the first endoscopic ultrasonographic report of an intraluminal mucin pool as a hypoechoic substance, which is quite different from the hyperechoic presentation of intramural mucin lakes. In preoperative evaluation, EUS is not only important for determining the depth of tumor invasion, but it is also useful in differentiating mucinous gastric carcinoma from nonmucinous gastric carcinoma.     

Multidrug-resistant tuberculosis. 5. Human immunodeficiency virus infection and multidrug-resistant tuberculosis

Outbreaks of multidrug-resistant tuberculosis (MDR-TB) among human immunodeficiency virus (HIV)-infected persons reported in the United States were very serious and the risks were increased by the delay of diagnosis, rapid progression from infection to active disease, inadequate therapy and poor tuberculosis (TB) control. Prevalence of drug-resistant TB among HIV-infected patients in Japan was studied. The results of drug susceptibility were collected through the nationwide working group for a survey of HIV-infected TB. Data of susceptibility for 39 cases were obtained. The isolates of two cases were resistant to isoniazid and rifampicin (including clinical failure of response), although no outbreak of MDR-TB was found in Japan. Case study of a patient who developed MDR-TB revealed that drug resistance might be selected by insufficient anti-TB therapy. The rate of resistance to any of the anti-TB drugs in HIV-infected patients seemed to be high, although strictly evaluation was difficult due to no standardization for drug susceptibility testing. Of 9 cases with resistance to any of the anti-TB drugs, 8 had extrapulmonary TB including 5 cases of disseminated TB. In contrast thirteen of 30 cases without drug resistance had extrapulmonary TB. Since it has been reported that HIV infection is related to increased rates of drug resistance of TB bacilli, treatment with four-drug regimen should be started and sufficient courses of therapy are needed in HIV-infected TB patients.     

Kinetics and toxicity of liposomal and conventional amikacin in a patient with multidrug-resistant tuberculosis

The pharmacokinetics and toxicity of liposomal amikacin in a patient treated for advanced pulmonary multidrug-resistant tuberculosis are described. A dose of 20 mg/kg of liposomal amikacin was given on alternate days for 14 days and weekly thereafter for 9 weeks, for a total dose of 20.1 g in 17 divided doses. Accumulation occurred with alternate-day, but not weekly, dosing. The serum levels of amikacin obtained with the liposomal preparation were considerably greater than those obtained with the conventional preparation (range, 81-457 mg/l vs. 4.1-37.7 mg/l). The liposomal amikacin was well tolerated and led to clinical improvement, but it failed to achieve a microbiological response. The patient's sputum remained smear- and culture-positive during the treatment period with liposomal amikacin and for 9 months afterward.     

Reinfection with the agent of human granulocytic ehrlichiosis

1. The functional role of the paraventricular nucleus (PVN) has been examined by studying its connections with cardiovascular neurons in the medulla and spinal cord and its influence on activity in several sympathetic nerves. 2. Chemical stimulation of neurons within the PVN can elicit pressor responses and can excite reticulo-spinal vasomotor neurons in the rostral ventrolateral medulla (RVLM). 3. The PVN-RVLM excitation is blocked by kynurenic acid applied iontophoretically in the vicinity of RVLM-spinal neurons, suggesting this is a glutamate-dependent pathway. 4. Electrical stimulation of PVN neurons evoked action potentials in RVLM neurons after 27 ms with a small variability. 5. Anterograde and retrograde labelling of PVN and RVLM neurons revealed PVN terminals closely associated with RVLM-spinal neurons and showed that the PVN is connected to the spinal cord via three pathways. 6. Chemical activation of PVN neurons can produce a pattern of activation of cardiovascular neurons similar to that occurring in defence against plasma volume expansion. 7. It is concluded that the PVN connections with the RVLM and spinal cord are important to a role in defending against life-threatening disturbances.     

Multidrug-resistant tuberculosis. Additional comment: primary multidrug-resistant tuberculosis--diagnosis and treatment

OBJECTIVE: To assess the effect of intra-articular corticosteroids added to systemic antibiotics in experimental septic arthritis. METHODS: Rabbits were injected intra-articularly by Staphylococcus epidermidis. Rabbits received no additional treatment and served as control (group 1), were treated with systemic antibiotics (group 2), or treated with systemic antibiotics and intra-articular corticosteroids (group 3). After 15 days animals were killed and joint histopathological-histochemical parameters were assessed. RESULTS: All rabbits survived the experiment. The treated groups (2-3) had lower histological-histochemical scores in comparison with the untreated group (1). Group 3 had significantly lower scores in joint sections in comparison with group 2: (mean (SD) 6.5 (1.4) v 4.0 (1.0), p = 0.001 and 7.4 (2.6) v 4.2 (2.2), p = 0.01), because of lower damage expressed in clustering of chondrocytes, pannus formation, proteoglycan depletion, and synovitis. CONCLUSION: Addition of local corticosteroids to systemic antibiotics in septic arthritis seems to be harmless, and improves joint histological-histochemical parameters in this experimental setting.     

Patients with multidrug-resistant tuberculosis with low CD4+ T cell counts have impaired Th1 responses

Canine lingual arteries are innervated by calcitonin gene-related peptide (CGRP)-containing vasodilator nerves. Although the vascular system might be considered as the first target of oxygen-derived free radicals in some of the pathophysiological conditions, the effect of oxygen-derived free radicals on neurotransmission in CGRP nerves remains unknown. We, therefore, investigated the role of oxygen-derived free radicals generated from Fenton's reagent (3 x 10(-4) M H2O2 plus 2 x 10(-4) M FeSO4) on CGRP-mediated neurogenic relaxation of canine lingual artery ring preparations. In all experiments, endothelium-denuded preparations (which were suspended in the tissue bath for isometric tension recordings) were treated with guanethidine (5 x 10(-6) M) to block neurogenic constrictor responses. The periarterial nerve stimulation (10 V, 4-16 Hz, for 45 sec), exogenous CGRP (10(-8) M) or the ATP-sensitive K+ channel opener cromakalim (10(-6) M) produced relaxation of the rings at a stable plateau tension by the addition of norepinephrine (10(-5) M); the relaxations elicited by CGRP and cromakalim were human CGRP-(8-37)- and glibenclamide-abolishable, respectively. When the nerve stimulation, CGRP and cromakalim were given after H2O2/FeSO4 exposure (Fenton's reagent was removed from the tissue bath), the observed relaxations were markedly diminished. The effects afforded by the early exposure to H2O2/FeSO4 reaction of the preparations were significantly protected by catalase (100 U/ml, H2O2 scavenger), dimethylthiourea (1 mM, H2O2 and HO. scavenger), dimethyl sulfoxide (100 mM, HO. scavenger), deferoxamine (1 mM, a powerful iron chelator) and by a cocktail of catalase-deferoxamine. Generation of HO. from H2O2/FeSO4 was studied by electron spin resonance spectroscopy using the spintrap 5,5-dimethyl-1-pyrroline-N-oxide. We found that H2O2/ FeSO4 reaction formed a 1:2:2:1 quartet, characteristic of the HO-5,5-dimethyl-1-pyrroline-N-oxide spin adduct. After exposure to capsaicin (10(-5) M) or H2O2/FeSO4 of the artery ring preparations, the intensity of CGRP-like immunoreactivity of the periarterial nerves was reduced drastically; the relaxation caused by the nerve stimulation was nearly fully inhibited by capsaicin and H2O2/FeSO4 reaction. The relaxant response, however, to nitroglycerin (10(-5) M) in the presence of norepinephrine to induce tone was unaffected by the early H2O2/ FeSO4 exposure. The data obtained from the present study indicate that HO., rather than H2O2, is the active agent in CGRP-mediated neurogenic relaxation. It is suggested that the HO. can deplete endogenous CGRP localized prejunctionally and also damage CGRP-induced relaxation of canine lingual artery preparations that is caused by activation of ATP-sensitive K+ channels at postjunctional sites. It is also postulated that the second messenger system of the relaxation mediated, at least, by cyclic GMP may be less susceptible to HO..     

Synergistic activities of clarithromycin and antituberculous drugs against multidrug-resistant Mycobacterium tuberculosis

The rise of multidrug-resistant Mycobacterium tuberculosis has complicated therapy for tuberculosis and led us to search for a potentially active combination of drugs against these strains. The susceptibilities of 12 strains of multidrug-resistant M. tuberculosis to standard antituberculous drugs (isoniazid, rifampin, ethambutol, and pyrazinamide), clarithromycin, and its metabolite, 14-hydroxyclarithromycin, were determined by use of the BACTEC radiometric method. All strains were resistant to at least two of the antituberculous drugs. Clarithromycin and 14-hydroxyclarithromycin MICs were in the range indicating resistance at > or = 8.0 micrograms/ml for all strains. Combination testing by the BACTEC method was performed with various concentrations of isoniazid, rifampin, and ethambutol, and with clarithromycin/14-hydroxyclarithromycin at fixed concentrations of 2.0/0.5 micrograms/ml, respectively. Addition of clarithromycin/14-hydroxyclarithromycin to these antituberculous drug mixtures resulted in a 4- to 32-fold reduction in MICs of isoniazid, rifampin, and ethambutol and made resistant strains susceptible. Fractional inhibitory concentrations ranged from 0.23 to 0.50 for all strains, suggesting a synergistic interaction between standard antituberculous drugs and clarithromycin/14-hydroxyclarithromycin. The ability of clarithromycin/14-hydroxyclarithromycin to enhance the activities of isoniazid, ethambutol, and rifampin in vitro suggests that this combination may be efficacious in the treatment of multidrug-resistant M. tuberculosis infections.     

Tuberculosis cutis miliaris disseminata due to multidrug-resistant Mycobacterium tuberculosis in AIDS patients

Two patients with AIDS and disseminated tuberculosis characterized by cutaneous involvement are reported. They developed a maculopapular skin eruption, from which a multidrug-resistant Mycobacterium tuberculosis strain was isolated. In both cases the clinical course was rapidly fatal. Tuberculosis cutis miliaris disseminata should be differentiated from the skin lesions frequently seen in HIV-infected patients, especially from folliculitis. In patients with tuberculosis, the appearance of cutaneous lesions may be due to the haematogenous dissemination of mycobacteria. Therefore, early identification of the causative organism by use of optimal microbiological methods is fundamental.     

Risk factors and outcome of human immunodeficiency virus-infected patients with sporadic multidrug-resistant tuberculosis in New York City

The discovery of neuroendocrine differentiation in hormone-refractory prostatic adenocarcinoma has opened a potentially new therapeutic approach in this group of patients with a poor prognosis and few effective therapy modalities. Based on previous findings of increased uptake of 11C-5-hydroxytryptophan (11C-5-HTP) in neuroendocrine tumours using the PET technique, this tracer was applied in the study of 10 patients with metastatic hormone-refractory prostatic adenocarcinoma. In three patients, the study was repeated after treatment. An increased uptake of 11C-5-HTP was observed in all investigated skeletal lesions, although the magnitude of the uptake was moderate. The difference between the standard uptake values (SUV) in normal bone and metastatic lesions was significant (p < 0.001). A kinetic analysis of the uptake of 11C-5-HTP demonstrates an increase during the first minutes followed by a wash-out and a stabilization of the tissue/blood ratio at about 2. The Patlak plots demonstrated a gradual increase in the transport rate during the first 20 to 30 min, after which a constant level was observed. The SUV varied between patients and between lesions over time and treatment. The uptake of 11C-5-HTP discriminates metastatic lesions from normal bone and may thus aid in the diagnosis and, potentially, in treatment monitoring of metastatic hormone-refractory prostatic adenocarcinoma. Uptake kinetics are characterized by a wash-out and cannot alone be used as proof of neuroendocrine differentiation in hormone-refractory prostatic adenocarcinoma.     

Use of adjunctive treatment with interferon-gamma in an immunocompromised patient who had refractory multidrug-resistant tuberculosis of the brain

We describe a patient with acute lymphocytic leukemia and multidrug-resistant tuberculosis of the brain and spinal cord. Despite treatment with six antituberculous drugs and a steroid medication for 11 months, there was no appreciable clinical or radiological improvement in the patient's condition. Within 5 months of initiating adjunctive therapy with IFN-gamma and granulocyte colony stimulating factors, substantial neurological and radiological improvement was noted. Therapy with IFN-gamma was continued for 12 months, resulting in complete resolution of the lesions in the brain and spinal cord.     

Contribution of beta-lactamases to beta-lactam susceptibilities of susceptible and multidrug-resistant Mycobacterium tuberculosis clinical isolates

The beta-lactamases in 154 clinical Mycobacterium tuberculosis strains were studied. Susceptibilities to beta-lactam antibiotics, their combination with clavulanate (2:1), and two fluoroquinolones were determined in 24 M. tuberculosis strains susceptible to antimycobacterial drugs and in nine multiresistant strains. All 154 M. tuberculosis isolates showed a single chromosomal beta-lactamase pattern (pI 4.9 and 5.1). M. tuberculosis beta-lactamase hydrolyzes cefotaxime with a maximum rate of 22.5 +/- 2.19 IU/liter (strain 1382). Neither amoxicillin, carbenicillin, cefotaxime, ceftriaxone, nor aztreonam was active alone. Except for aztreonam, beta-lactam combinations with clavulanate produced better antimycobacterial activity.     

Reinfection with Schistosoma japonicum after treatment with praziquantel in Poyang lake region, China

The study on reinfection with Schistosoma japonicum after treatment was carried out in a cohort of subjects in a heavy endemic village of Poyang lake region, China. After mass treatment with praziquantel in non-transmission time, detailed observations of water contact were estimated using the mean area of skin exposed daily. One year after treatment, the prevalence of infection in study subjects was 54.48%, returning to 83% of initial prevalence. The peak prevalence occurred the 11-15 year age class, but intensity of exposure also varies with age and that age group supporting the higher prevalence of reinfection had high levels of exposure. Among groups of subjects with a similar exposure stratum, young subjects under the age of 21 years were more heavily reinfected, while no heavy reinfection was observed in adults (> or = 25 years). These observations suggest that subjects in this area slowly acquire an increasing degree of immunity to lighten the intensity of infection with S. japonicum.     

Bactericidal activities of the pyrrole derivative BM212 against multidrug-resistant and intramacrophagic Mycobacterium tuberculosis strains

The pyrrole derivative BM212 [1, 5-diaryl-2-methyl-3-(4-methylpiperazin-1-yl)methyl-pyrrole] was shown to possess strong inhibitory activity against both Mycobacterium tuberculosis and some nontuberculosis mycobacteria. BM212 was inhibitory to drug-resistant mycobacteria and also exerted bactericidal activity against intracellular bacilli residing in the U937 human histiocytic lymphoma cell line.     

Efficacy of control measures in preventing nosocomial transmission of multidrug-resistant tuberculosis to patients and health care workers

OBJECTIVE: To assess the efficacy of control measures in decreasing nosocomial transmission of multidrug-resistant tuberculosis. DESIGN: Retrospective cohort study. SETTING: A teaching hospital in New York City. POPULATION: 40 patients hospitalized with multidrug-resistant tuberculosis (case-patients) and health care workers receiving tuberculin skin testing. INTERVENTIONS: Centers for Disease Control and Prevention (CDC) 1990 guidelines for preventing transmission of tuberculosis, including 1) prompt isolation and treatment of patients with tuberculosis; 2) rapid diagnostic techniques for processing Mycobacterium tuberculosis specimens; 3) negative-pressure isolation rooms; and 4) molded surgical masks for health care workers. MEASUREMENTS: Proportion of case-patients with nosocomially acquired tuberculosis and rate of tuberculin skin test conversion among health care workers before and after implementation of control measures. RESULTS: The proportion of patients with multidrug-resistant strains of M. tuberculosis decreased after the interventions (10 of 70 [14%] compared with 30 of 95 [32%] patients before the intervention; relative risk [RR], 0.5; 95% CI, 0.2 to 0.9). Before onset of multidrug-resistant tuberculosis, case-patients in the intervention period were as likely to be hospitalized on high-risk wards containing patients with tuberculosis (4 of 10 compared with 17 of 30 patients; RR, 0.7; P = 0.5) but were less likely to be exposed to another case-patient with tuberculosis (1 of 10 compared with 20 of 30 patients; RR, 0.2; P = 0.003). Tuberculin skin test conversion rates for health care workers assigned to wards housing patients with tuberculosis were lower in the intervention period than in the preintervention period (4 of 78 [5%] compared with 15 of 90 [17%] conversions; P = 0.02), decreasing to levels observed for workers assigned to other wards (4 of 78 [5%] compared with 9 of 228 [4%] conversions; P = 0.7). CONCLUSIONS: Implementing control measures reduced nosocomial transmission of multidrug-resistant strains to patients and health care workers.     

Attributable factors to the emergence of multidrug-resistant Mycobacterium tuberculosis based on the observation of consecutive drug resistance test results

Determining whether there is evidence of underutilization of outpatient mental health care by Department of Defense (DoD) beneficiaries relative to the general population is the purpose of this study. It analyzes data from the 1994-1995 DoD Health Beneficiary Survey and compares the mental health status and usage rates of active duty members and their families with benchmark levels found in the general population. Although the mental health status for the DoD beneficiary population was found to be generally the same as that of the general U.S. population within gender categories, gender-specific usage rates of mental health services of DoD beneficiaries in the groups examined were well below rates recorded for the general population. The concept of psychological readiness is also introduced. Several recommendations for increasing access to mental health care are presented.     

Temporal trends and transmission patterns during the emergence of multidrug-resistant tuberculosis in New York City: a molecular epidemiologic assessment

To ascertain the role of human immunodeficiency virus (HIV) and Mycobacterium tuberculosis transmission on multidrug-resistant (MDR) tuberculosis (TB) emergence in New York City, medical records, drug susceptibilities, and restriction fragment length polymorphisms (RFLPs) of TB cases at a city hospital between two 9-month periods (1987-1988 and 1990-1991) were reviewed. The proportion of TB patients with MDRTB increased from 10% (27/267) to 17% (38/222; P = .03). Among MDRTB patients of known HIV status, the proportion with HIV increased from 16% (3/19) to 58% (22/38; P = .006). HIV-infected MDRTB patients were more likely than the seronegative ones to have initial MDRTB (88% vs. 56%; P = .03). Among 56 MDR cases with RFLP results, 12 had unique patterns; 44 belonged to one of six clusters. During 1990-1991, 27 (75%) of 36 MDRTB patients were infected with strains isolated from HIV-seronegative patients during 1987-1988. The increase in MDRTB caused by transmission from immunocompetent to immunocompromised persons underscores the urgency of TB control in populations with increasing HIV prevalence.