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1.
Infection ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38955990

RESUMEN

Paradoxical reactions (PR) to tuberculosis (TB) treatment are common during treatment, but have also been described after treatment. A presentation with recurrent signs or symptoms of TB after cure or completion of prior treatment needs to be differentiated between microbiological relapse and a paradoxical reaction. We searched all published literature on post-treatment PR, and present a synthesis of 30 studies, focusing on the epidemiology, diagnosis and management of this phenomenon. We report an additional case vignette. The majority of studies were of lymph node TB (LN-TB), followed by central nervous system TB (CNS-TB). A total of 112 confirmed and 42 possible post-treatment PR cases were reported. The incidence ranged between 3 and 14% in LN-TB and was more frequent than relapses, and between 0 and 2% in all TB. We found four reports of pulmonary or pleural TB post-treatment PR cases. The incidence did not differ by length of treatment, but was associated with younger age at initial diagnosis, and having had a PR (later) during treatment. Post-treatment PR developed mainly within the first 6 months after the end of TB treatment but has been reported many years later (longest report 10 years). The mainstays of diagnosis and management are negative mycobacterial cultures and anti-inflammatory treatment, respectively. Due to the favourable prognosis in LN-TB recurrent symptoms, a short period of observation is warranted to assess for spontaneous regression. In CNS-TB with recurrent symptoms, immediate investigation and anti-inflammatory treatment with the possibility of TB retreatment should be undertaken.

2.
J Endocrinol Invest ; 47(1): 213-221, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37344722

RESUMEN

OBJECTIVE: A paradoxical GH rise after the glucose load (GH-Par) is described in about one-third of acromegalic patients. Here, we evaluated the GH profile in subjects with and without acromegaly aiming to refine the definition of GH-Par. DESIGN: Observational case-control study. METHODS: Our cohort consisted of 60 acromegalic patients, and two groups of subjects presenting suppressed GH (< 0.4 µg/L) and high (non-acro↑IGF-1, n = 116) or normal IGF-1 levels (non-acro, n = 55). The distribution of GH peaks ≥ 120% from baseline, insulin, and glucose levels were evaluated over a 180-min time interval after glucose intake. RESULTS: A similar proportion of subjects in all three groups shows a GH ratio of ≥ 120% starting from 120 min. Re-considering the definition of paradoxical increase of GH within 90 min, we observed that the prevalence of GH peaks ≥ 120% was higher in acromegaly than in non-acro↑IGF-1 and non-acro (respectively 42%, 16%, and 7%, both p < 0.001). In patients without GH-Par, a late GH rebound was observed in the second part of the curve. Higher glucose peak (p = 0.038), slower decline after load, 20% higher glucose exposure (p = 0.015), and a higher prevalence of diabetes (p = 0.003) characterized acromegalic patients with GH-Par (with respect to those without). CONCLUSIONS: GH-Par response may be defined as a 20% increase in the first 90 min after glucose challenge. GH-Par, common in acromegaly and associated with an increased prevalence of glucose metabolism abnormalities, is found also in a subset of non-acromegalic subjects with high IGF-1 levels, suggesting its possible involvement in the early phase of the disease.


Asunto(s)
Acromegalia , Hormona de Crecimiento Humana , Humanos , Acromegalia/epidemiología , Acromegalia/metabolismo , Glucosa/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Hormona de Crecimiento Humana/metabolismo , Estudios de Casos y Controles
3.
J Infect Chemother ; 29(9): 890-894, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37244351

RESUMEN

BACKGROUND: Patients with pulmonary tuberculosis may present with deterioration of pleural effusion during anti-tuberculosis therapy, referred to as a paradoxical response (PR), with some patients requiring additional intervention. However, PR may be confused with other differential diagnoses, and the predictive factors for recommending additional therapies are unknown. Therefore, this study aimed to reveal useful information for the diagnosis and intervention of PR. METHODS: Data from human immunodeficiency virus-negative patients with tuberculous pleurisy (n = 210), including 184 patients with pre-existing pleural effusion and 26 patients with PR at Fukujuji Hospital, were retrospectively collected from January 2012 to December 2022 and compared. Furthermore, patients with PR were divided into the intervention group (n = 9) and the no intervention group (n = 17) and were compared. RESULTS: Patients in the PR group had lower pleural lactate dehydrogenase (LDH) (median 177 IU/L vs. 383 IU/L, p < 0.001) and higher pleural glucose (median 122 mg/dL vs. 93 mg/dL, p < 0.001) levels than those in the preexisting pleural effusion group. Other pleural fluid data were not significantly different. Patients in the intervention group had a shorter duration from the initiation of anti-tuberculosis therapy to the development of PR than patients in the no intervention group (median 19.0 days [interquartile range (IQR): 18.0-22.0] vs. median 37.0 days [IQR: 28.0-58.0], p = 0.012). CONCLUSION: This study demonstrates that, apart from lower pleural LDH and elevated pleural glucose levels, PR presents with similar features to preexisting pleural effusion and that patients who develop PR faster tend to require intervention.


Asunto(s)
Derrame Pleural , Tuberculosis Pleural , Tuberculosis Pulmonar , Humanos , Estudios Retrospectivos , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pleural/complicaciones , Tuberculosis Pleural/diagnóstico , Tuberculosis Pleural/tratamiento farmacológico , L-Lactato Deshidrogenasa , Antituberculosos/uso terapéutico , Glucosa/uso terapéutico
4.
J Korean Med Sci ; 38(47): e348, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38050909

RESUMEN

BACKGROUND: Paradoxical responses (PR) occur more frequently in lymph node tuberculosis (LNTB) than in pulmonary tuberculosis and present difficulties in differential diagnosis of drug resistance, new infection, poor patient compliance, and adverse drug reactions. Although diagnosis of mediastinal LNTB has become much easier with the development of endosonography, limited information is available. The aim of this study was to investigate the clinical course of mediastinal LNTB and the risk factors associated with PR. METHODS: Patients diagnosed with mediastinal LNTB via endosonography were evaluated retrospectively between October 2009 and December 2019. Multivariable logistic regression was applied to evaluate the risk factors associated with PR. RESULTS: Of 9,052 patients who underwent endosonography during the study period, 158 were diagnosed with mediastinal LNTB. Of these, 55 (35%) and 41 (26%) concurrently had pulmonary tuberculosis and extrapulmonary tuberculosis other than mediastinal LNTB, respectively. Of 125 patients who completed anti-tuberculosis treatment, 21 (17%) developed PR at a median of 4.4 months after initiation of anti-tuberculosis treatment. The median duration of anti-tuberculosis treatment was 6.3 and 10.4 months in patients without and with PR, respectively. Development of PR was independently associated with age < 55 years (adjusted odds ratio [aOR], 5.72; 95% confidence interval [CI], 1.81-18.14; P = 0.003), lymphocyte count < 800/µL (aOR, 8.59; 95% CI, 1.60-46.20; P = 0.012), and short axis diameter of the largest lymph node (LN) ≥ 16 mm (aOR, 5.22; 95% CI, 1.70-16.00; P = 0.004) at the time of diagnosis of mediastinal LNTB. CONCLUSION: As PR occurred in one of six patients with mediastinal LNTB during anti-tuberculosis treatment, physicians should pay attention to patients with risk factors (younger age, lymphocytopenia, and larger LN) at the time of diagnosis.


Asunto(s)
Tuberculosis Ganglionar , Tuberculosis Pulmonar , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Tuberculosis Ganglionar/diagnóstico , Tuberculosis Ganglionar/tratamiento farmacológico , Tuberculosis Ganglionar/patología , Ganglios Linfáticos/patología , Factores de Riesgo , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/tratamiento farmacológico , Antituberculosos/uso terapéutico , Progresión de la Enfermedad
5.
Prostate ; 82(16): 1483-1490, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36089822

RESUMEN

BACKGROUND: Prostatic specific antigen (PSA) has well-recognized limitations as a marker for treatment response and disease progression. Post hoc analysis of the PREVAIL trial reported 24.5% of chemotherapy naïve metastatic castration-resistant prostate cancer (mCRPC) patients on enzalutamide had radiographic progression on conventional imaging with nonrising PSA. In this study, we sought to study the discordance of imaging with PSA kinetics in mCRPC patients on second generation anti-androgens (SGA) post-chemotherapy using combined conventional imaging, and new generation imaging in the form of C-11 choline positron emission tomography/computed tomography (C[11] choline PET/CT) scan. METHODS: We retrospectively reviewed the medical records of 123 patients with mCRPC treated with SGA (Abiraterone or Enzalutamide) after docetaxel between 2016 and 2019. Patients underwent PSA testing, and C[11] choline PET/CT scan at baseline level before starting treatment with SGA, then every 3-6 months as part of their follow up evaluation. Loss of response to SGA was defined by increase in corrected maximum standardized uptake value (SUVmax) of pretreatment lesions on C-11 Choline PET/CT, and/or development of new lesions. Suspicious new lesions were confirmed by biopsy and/or conventional imaging. RESULTS: We identified 123 mCRPC patients who received SGA (Abiraterone, n = 106; Enzalutamide, n = 17) after docetaxel. Median duration of therapy was 13.9 months (interquartile range: 8.75-21.14). Approximately 43% (n = 53) of subjects in this study exhibited an increase in choline avidity while on SGA. Of this group, 60.4% of patients experienced a parallel rise in PSA (Group-A), whereas 39.6% displayed a paradoxical response (PR) (Group-B), defined as increased choline avidity combined with stable or down-trending PSA. Median PSA at time of increase in choline avidity was 3.1 ng/ml for Group-A, and 1.3 ng/ml for Group-B (p = 0.0176). Median SUVmax was similar in both groups (4.9 for Group-A, 4.6 for Group-B; p = 0.6072). The median time for increase in choline avidity was 9.5 versus 3.9 months for Group-A versus Group-B, respectively (Log-Rank = 0.0063). CONCLUSION: Nearly 40% of mCRPC patients placed on SGA post docetaxel chemotherapy will exhibit paradoxical responses to therapy, therefore, warranting close follow up with imaging. C-11 choline PET/CT imaging is a useful tool that can help in early predication of disease progression or treatment failure.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Humanos , Masculino , Antagonistas de Andrógenos/uso terapéutico , Colina , Progresión de la Enfermedad , Docetaxel/uso terapéutico , Tomografía Computarizada por Tomografía de Emisión de Positrones , Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico por imagen , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Radiofármacos/uso terapéutico , Estudios Retrospectivos , Resultado del Tratamiento
6.
J Infect Chemother ; 25(1): 54-58, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30055859

RESUMEN

Anti-programmed cell death-1 (PD-1) agents enhance the antitumor immunoresponse. A number of reports have indicated that patients with malignancies who receive anti-PD-1 agents are at risk for tuberculosis (TB) infection. In this report, we present a patient with non-small cell lung cancer who developed pulmonary tuberculosis while receiving the anti-PD-1 agent nivolumab, and who subsequently demonstrated a paradoxical response (PR) 10 days after initiation of anti-MTB treatment. We suggest that anti-PD-1 agents not only induce the development of pulmonary TB, but also development of PR after anti-MTB treatment, through upregulation of the immune response. Furthermore, based on their radiological and immunological similarity, we speculate that the schema of development of PR closely resembles that of pseudoprogression in non-small cell lung cancer patients after anti-PD-1 treatment.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antibacterianos/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Nivolumab/administración & dosificación , Adenocarcinoma/complicaciones , Anciano , Antibacterianos/uso terapéutico , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/genética , Humanos , Pulmón/patología , Neoplasias Pulmonares/complicaciones , Masculino , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Nivolumab/uso terapéutico , Esputo/microbiología , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiología
7.
Arerugi ; 68(6): 691-695, 2019.
Artículo en Japonés | MEDLINE | ID: mdl-31308335

RESUMEN

BACKGROUND: Paradoxical response (PR) is defined as a clinical or radiological worsening in patients receiving adequate anti-tuberculosis treatment, with the exclusion of documented relapse or of other disease presentations. Although most patients with PR show spontaneous improvement, some cases presenting with diffuse alveolar damage have also been reported. METHODS: Retrospective clinical and laboratory data were collected on 89 patients of pulmonary tuberculosis who were treated at our hospital between April 2013 and January 2019. RESULTS: PR occurred in 21 patients (24%), and the median onset time after anti-tuberculosis treatment was 22 days. The time to onset of PR was shorter in diffuse pulmonary infiltrates group than in local pulmonary infiltrates group or in pleural effusion group. Low serum albumin, elevated lactate dehydrogenase (LDH), high Creactive protein (CRP) and chest radiographic appearance exceeding one-lung area were associated with PR incidence. There was no difference in sputum smear grading and pulmonary cavitation. Six out of the ten patients died, developing PR with diffuse pulmonary infiltrates. CONCLUSION: Low albumin and chest radiographic appearance exceeding one-lung area were risk factors for developing PR. Diffuse pulmonary infiltrates in early phase of anti-tuberculosis treatment was related with Inhospital mortality.


Asunto(s)
Tuberculosis Pulmonar/diagnóstico por imagen , Tuberculosis Pulmonar/tratamiento farmacológico , Proteína C-Reactiva/análisis , Mortalidad Hospitalaria , Humanos , Incidencia , L-Lactato Deshidrogenasa/sangre , Radiografía , Radiografía Torácica , Estudios Retrospectivos , Factores de Riesgo , Albúmina Sérica Humana/análisis , Esputo , Resultado del Tratamiento
8.
BMC Neurol ; 18(1): 10, 2018 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-29347976

RESUMEN

BACKGROUND: Central nervous system (CNS) tuberculoma is a rare disease with severe neurological deficits. This retrospective research is to review the data of patients diagnosed as CNS tuberculoma. Surgeries were performed in all patients. The clinical features especially the neurological image and the anatomical characters of the tuberculomas were concerned. METHODS: Totally 11 patients diagnosed as CNS tuberculoma were admitted in Guangzhou First People's Hospital (7cases) and Changzheng Hospital (4 cases) during 2006-2015. The data including preoperative condition, neurological imaging, and surgical findings was collected and analyzed. RESULTS: The lesions of nine patients (9/11) were totally or subtotally excised and two (2/11) were partially excised. Neurological functions of all patients were improved after surgery without secondary infection. Lesions of nine (9/11) patients preoperatively progressed as a result of paradoxical reaction. Of the 9 patients demonstrated paradoxical progression, all lesions were partially or totally located at the cisterns or the subarachnoid space. Preoperative ATTs lasted 2 to 12 months and tuberculomas were not eliminated. The arachnoid was found thickened and tightly adhered to the lesions during surgeries. Of the 2 cases that paradoxical reaction were excluded, both patients (case 6, intramedullary tuberculoma; case 11, intradural extramedullary tuberculoma) were admitted at onset of the disease. ATTs were preoperatively given for 1 week as neurological deficits aggravated. The tuberculous lesions of CNS or other system showed no obvious change and paradoxical reaction could not be established in both cases. CONCLUSIONS: Exudates of tuberculosis is usually accumulated in the cisterns and frequently results in the paradoxical formation of tuberculoma. Intracisternal tuberculoma is closely related to paradoxical reaction and refractory to anti-tuberculosis therapy. Micro-surgical excision is safe and effective. Early surgical intervention may be considered in the diagnosis of intracisternal tuberculoma especially when paradoxical reaction participates in the development of tuberculoma.


Asunto(s)
Antituberculosos/uso terapéutico , Tuberculoma/diagnóstico , Adolescente , Adulto , Niño , Progresión de la Enfermedad , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tuberculoma/terapia , Adulto Joven
9.
J Clin Ultrasound ; 45(1): 58-61, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27444317

RESUMEN

Patent foramen ovale (PFO) is a frequent congenital anomaly, but massive right-to-left shunt (RTLS) is normally prevented by higher pressures in left heart chambers. However, mechanical ventilation with positive end-expiratory pressure (PEEP) can significantly increase right atrial pressure, accentuating the RTLS, mainly after major cardiothoracic surgery. We report a patient admitted to the intensive care unit after cardiac surgery. Pre- and intraoperative transesophageal echocardiography only described an aneurysmal interatrial septum with no shunt. However, high-PEEP ventilation induced a paradoxical response with life-threatening hypoxemia, triggering further echocardiographic evaluation, revealing massive RTLS across a stretch PFO. Provocative maneuvers (Valsalva/PEEP) significantly increase echocardiographic sensitivity, unmasking silent PFO. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:58-61, 2017.


Asunto(s)
Ecocardiografía Transesofágica/métodos , Foramen Oval Permeable/diagnóstico por imagen , Respiración con Presión Positiva , Ultrasonografía Doppler en Color/métodos , Maniobra de Valsalva , Anciano , Foramen Oval Permeable/fisiopatología , Humanos , Masculino
10.
Z Rheumatol ; 76(4): 372-374, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28124746

RESUMEN

Tumor necrosis factor alpha (TNF-α) inhibitors effectively treat sarcoidosis, but can, paradoxically, induce sarcoidosis. The TNF-α inhibitor etanercept is most commonly associated with paradoxical sarcoidosis, which has previously been reported to be resolved by adalimumab. However, we describe the case of a patient with ankylosing spondylitis and adalimumab-induced sarcoidosis not aggravated by switching to etanercept, thus indicating that etanercept could be a treatment option for patients who develop paradoxical sarcoid-like reactions after treatment with other TNF-α inhibitors.


Asunto(s)
Adalimumab/efectos adversos , Etanercept/uso terapéutico , Sarcoidosis Pulmonar/inducido químicamente , Sarcoidosis Pulmonar/tratamiento farmacológico , Adulto , Progresión de la Enfermedad , Sustitución de Medicamentos/efectos adversos , Sustitución de Medicamentos/métodos , Humanos , Masculino , Sarcoidosis Pulmonar/diagnóstico , Resultado del Tratamiento
11.
BMC Infect Dis ; 16: 284, 2016 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-27297079

RESUMEN

BACKGROUND: Early postpartum women are more likely to develop tuberculosis than nonpregnant women mainly due to immune reconstitution after delivery. Paradoxical response (PR) during antituberculosis treatment also arises via recovery from immunosuppression. However, no study focused on PR during antituberculosis treatment in a postpartum patient has been reported. CASE PRESENTATION: We present two sequential cases (Patient 1: 26-year-old; Patient 2: 29-year-old) of postpartum tuberculosis with pulmonary and extrapulmonary lesions (Patient 1: peritonitis; Patient 2: psoas abscess secondary to spondylitis). Both cases progressed to PR (worsening of pre-existing lung infiltrations (Patients 1, 2) and new contralateral effusion (Patient 2)) in a relatively short time after initiation of treatment (Patient 1: 1 week; Patient 2: 3 weeks), suggesting that immune modulations during pregnancy and delivery may contribute to the pathogenesis of both disseminated tuberculosis and its PR. The pulmonary lesions and effusion of both cases gradually improved without change of chemotherapy regimen. CONCLUSION: Physicians should recognize PR in tuberculosis patients with postpartum and then evaluate treatment efficacy.


Asunto(s)
Antituberculosos/uso terapéutico , Peritonitis Tuberculosa/tratamiento farmacológico , Absceso del Psoas/tratamiento farmacológico , Infección Puerperal/tratamiento farmacológico , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis de la Columna Vertebral/tratamiento farmacológico , Enfermedad Aguda , Adulto , Progresión de la Enfermedad , Femenino , Humanos , Peritonitis Tuberculosa/diagnóstico por imagen , Peritonitis Tuberculosa/inmunología , Periodo Posparto/inmunología , Embarazo , Absceso del Psoas/diagnóstico por imagen , Absceso del Psoas/etiología , Absceso del Psoas/inmunología , Infección Puerperal/diagnóstico por imagen , Infección Puerperal/inmunología , Radiografía Torácica , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Tuberculosis Pulmonar/diagnóstico por imagen , Tuberculosis Pulmonar/inmunología , Tuberculosis de la Columna Vertebral/complicaciones , Tuberculosis de la Columna Vertebral/diagnóstico por imagen , Tuberculosis de la Columna Vertebral/inmunología
12.
Pituitary ; 19(6): 605-611, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27639583

RESUMEN

PURPOSE: Pasireotide is the only pituitary targeted medication registered for the treatment of Cushing's disease. Drug efficacy data are largely based on a major prospective study in which the vast majority of patients had microadenomas. The purpose of this study was to summarize results of pasireotide treatment of ACTH secreting macroadenomas from our center. METHODS: Retrospective review of data extracted from clinical files. RESULTS: Three patients presented with large and invasive macroadenomas that required several surgical interventions and radiotherapy treatments. Patient 1 is a 57 year-old male who developed an extreme (27-fold) paradoxical response of urinary free cortisol (UFC) levels as measured 2 weeks after pasireotide institution, which increased further (71-fold) in response to dose increment but decreased to baseline levels after treatment interruption. Patient 2 is a 44 year old woman with a long standing (26 years) ACTH-secreting carcinoma metastatic to bone and after bilateral adrenalectomy. After an initial excellent response to pasireotide treatment, ACTH levels escaped suppression and a further rebound was noted 6 weeks after treatment interruption. Patient 3 is a 53 year old man that after escape from temozolomide therapy was started on pasireotide and rapidly responded by almost normalizing UFC excretion after 4 weeks, but returned to baseline UFC levels after four additional weeks of treatment. CONCLUSIONS: We describe as yet unreported atypical responses to pasireotide treatment in patients with aggressive ACTH-secreting tumors. Increased vigilance is recommended during pasireotide treatment of such patients.


Asunto(s)
Adenoma Hipofisario Secretor de ACTH/tratamiento farmacológico , Adenoma/tratamiento farmacológico , Hormona Adrenocorticotrópica/metabolismo , Somatostatina/análogos & derivados , Adenoma Hipofisario Secretor de ACTH/metabolismo , Adenoma/metabolismo , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Somatostatina/uso terapéutico , Resultado del Tratamiento
14.
Lett Appl Microbiol ; 60(5): 440-6, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25585891

RESUMEN

UNLABELLED: Growth of enteropathogenic Escherichia coli E2348/69 was inhibited by bicarbonate in a dose-dependent manner, showing approximately 5% growth reduction at 5 mmol l(-1) while kanamycin at 3·12 µg ml(-1) inhibited growth by 15%, yet when kanamycin and bicarbonate were combined at these concentrations, inhibition increased to 80%. Unexpectedly, at bicarbonate concentrations >20 mmol l(-1) enhancement of the antibiotic activity virtually disappeared, i.e. there was a paradoxical Eagle-like effect. How bicarbonate acts is unclear, but neutral or alkaline pH also enhanced the activity of kanamycin. However, several differences indicated a separate effect of bicarbonate. First, bicarbonate inhibited growth more than the corresponding increments in pH. Second, at low concentration, the antibiotic enhancing effect of bicarbonate was stronger than the effect of pH alone. Third, 5 mmol l(-1) bicarbonate significantly enhanced the activity of kanamycin while the corresponding pH had no effect. Fourth, the Eagle-like effect was exclusive of bicarbonate because changes in pH did not induce an analogous behaviour. Notwithstanding the mechanism, the enhancing effect of bicarbonate was indubitable. Consequently, it seems worthwhile to explore further its potential to improve the efficacy of aminoglycosides and maybe even other antibiotics. SIGNIFICANCE AND IMPACT OF THE STUDY: Bicarbonate at a low concentration enhanced the in vitro antibiotic activity of kanamycin and gentamicin. Even though the action mechanism of bicarbonate is hitherto unknown, it seems worthwhile to explore further its capacity to improve the efficacy of aminoglycosides. Clearly, the well-known harmful side-effects of aminoglycosides are a concern. However, it has recently been shown in a fish model that bicarbonate may protect ciliary cells against the damage caused by aminoglycosides. So, it seems possible that bicarbonate could help reduce aminoglycoside dosage at the same time that it might help lessen the damage to auditory ciliary cells in humans.


Asunto(s)
Bicarbonatos/farmacología , Escherichia coli/efectos de los fármacos , Gentamicinas/farmacología , Kanamicina/farmacología , Animales , Antibacterianos/farmacología , Gentamicinas/efectos adversos , Humanos , Técnicas In Vitro , Kanamicina/efectos adversos , Pruebas de Sensibilidad Microbiana
15.
Neural Netw ; 166: 296-312, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37541162

RESUMEN

Strong inhibitory recurrent connections can reduce the tendency for a neural network to become unstable. This is known as inhibitory stabilization; networks that are unstable in the absence of strong inhibitory feedback because of their unstable excitatory recurrent connections are known as Inhibition Stabilized Networks (ISNs). One of the characteristics of ISNs is their "paradoxical response", where perturbing the inhibitory neurons with additional excitatory input results in a decrease in their activity after a temporal delay instead of increasing their activity. Here, we develop a model of populations of neurons across different layers of cortex. Within each layer, there is one population of inhibitory neurons and one population of excitatory neurons. The connectivity weights across different populations in the model are derived from a synaptic physiology database provided by the Allen Institute. The model shows a gradient of excitation-inhibition balance across different layers in the cortex, where superficial layers are more inhibitory dominated compared to deeper layers. To investigate the presence of ISNs across different layers, we measured the membrane potentials of neural populations in the model after perturbing inhibitory populations. The results show that layer 2/3 in the model does not operate in the ISN regime but layers 4 and 5 do operate in the ISN regime. These results accord with neurophysiological findings that explored the presence of ISNs across different layers in the cortex. The results show that there may be a systematic macroscopic gradient of inhibitory stabilization across different layers in the cortex that depends on the level of excitation-inhibition balance, and that the strength of the paradoxical response increases as the model moves closer to bifurcation points.


Asunto(s)
Corteza Cerebral , Neuronas , Neuronas/fisiología , Corteza Cerebral/fisiología , Redes Neurales de la Computación , Potenciales de la Membrana , Inhibición Neural/fisiología
16.
Infect Drug Resist ; 16: 6629-6634, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37840829

RESUMEN

Amikacin liposome inhalation suspension (ALIS) is a key drug for the treatment of refractory Mycobacterium avium complex pulmonary disease (MAC-PD). Although cases of drug-induced interstitial lung disease (DIILD) by ALIS have been reported, its diagnosis is challenging due to overlapping existing pulmonary shadows, airway bleeding, exacerbation of underlying conditions, and the potential for various concurrent infections. A 72-year-old woman started treatment with ALIS for refractory MAC-PD. Three weeks later, she had a fever, cough, and appetite loss. She was hospitalized because multiple infiltrative opacities were observed on chest X-ray and chest computed tomography. Because the opacities worsened after empiric antibiotic therapy with broad-spectrum antibiotics, we initiated corticosteroid therapy, suspecting DIILD caused by ALIS, although drug lymphocyte stimulation tests for ALIS and amikacin were negative. Three days later, we found signs of improvement and quickly tapered the corticosteroids. After obtaining informed consent, we performed a drug provocation test of ALIS. Seven days later, she exhibited fever, an increased peripheral white blood cell count, and elevated serum C-reactive protein level, all of which returned to baseline 4 days after stopping ALIS, leading to a diagnosis of DIILD caused by ALIS in this patient. DIILD caused by ALIS is rare but should be carefully diagnosed to ensure that patients with refractory MAC-PD do not miss the opportunity to receive ALIS treatment.

19.
Med ; 3(9): 603-611.e2, 2022 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-36041428

RESUMEN

BACKGROUND: Paradoxical inflammatory responses can occur during microbiologically successful antituberculous therapy. Optimal treatment is unknown, but corticosteroids are used most often. It is likely that interleukin-1 (IL-1) plays a central role in the development of these paradoxical responses, and if corticosteroids fail or are undesirable because of adverse effects, anti-IL-1 therapy may therefore be a rational choice. METHODS: We present seven HIV-negative tuberculosis patients with paradoxical responses, two with exclusively pulmonary and five with extrapulmonary tuberculosis. All had received corticosteroids, with unsatisfactory effect. Patients were treated with the IL-1 receptor antagonist anakinra and monitored for reduction of fever and inflammatory markers, imaging evidence of stabilization or regression of lesions, and respiratory improvement. FINDINGS: Six patients had anemia and four patients had lymphopenia at the start of the antituberculosis treatment. Fever was present in six patients at the moment of paradoxical response. Anakinra resulted in the decrease of fever within days, followed by resolution of symptoms and radiological improvement in five patients. Anakinra induced neutropenia, necessitating its cessation in two patients, who recovered quickly afterward. CONCLUSION: Anakinra can be considered in HIV-negative tuberculosis patients with paradoxical responses when steroids fail or are undesired. Given its favorable safety profile and reversible side effects, it is conceivable that anakinra might also be used as first-line adjuvant treatment for paradoxical responses. FUNDING: A.v.L. and R.v.C. are supported by National Institutes of Health (R01AI145781).


Asunto(s)
Infecciones por VIH , Tuberculosis , Infecciones por VIH/complicaciones , Humanos , Proteína Antagonista del Receptor de Interleucina 1/efectos adversos , Receptores de Interleucina-1 , Resultado del Tratamiento , Tuberculosis/tratamiento farmacológico , Estados Unidos
20.
Front Neurol ; 13: 936837, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35983432

RESUMEN

Background and Purpose: Intraspinal tuberculoma is a rare disease in children, and its imaging findings have been described in only a few case reports. This study aimed to investigate the magnetic resonance imaging (MRI) features of pediatric intraspinal tuberculoma and to explore the possible pathogenesis of the disease. Materials and Methods: The clinical and MRI data of 24 child patients with intraspinal tuberculoma (such as 6 cases of intramedullary tuberculoma, 8 cases of intradural extramedullary tuberculoma, and 10 cases of epidural tuberculoma) were retrospectively analyzed. All patients underwent plain and contrast-enhanced MR scans. The diagnosis was confirmed by surgical pathology or by antituberculous treatment and follow-up data. Results: Intramedullary tuberculoma had a round shape, while intradural extramedullary tuberculoma and epidural tuberculoma presented long-fusiform or en plaque shapes. Regarding MRI signals, intramedullary tuberculoma and extramedullary tuberculoma were mainly isointense on T1-weighted imaging (T1WI) and hypointense or isointense on T2WI. Rim enhancement was observed in intramedullary tuberculoma, and marked homogeneous enhancement was dominant in extramedullary tuberculoma. Ten (10/24) tuberculomas occurred during antituberculous therapy, with intradural extramedullary tuberculoma accounting for 7 cases (7/8), which was significantly more frequent than intramedullary tuberculoma (1/6) or epidural tuberculoma (2/10). Conclusion: MRI is important in the diagnosis of intraspinal tuberculoma, which is characterized by isointensity on T1WI, isointensity, or hypointensity on T2WI, and rim or obvious homogeneous enhancement. Some intraspinal tuberculomas, especially intradural extramedullary tuberculomas, might be associated with the "paradoxical response" mechanism during the tuberculosis treatment.

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