Chronic changes in oligodendrocyte sub-populations after middle cerebral artery occlusion in neonatal mice.

Neonatal stroke is common and causes life-long motor and cognitive sequelae. Because neonates with stroke are not diagnosed until days-months after the injury, chronic targets for repair are needed. We evaluated oligodendrocyte maturity and myelination and assessed oligodendrocyte gene expression changes using single cell RNA sequencing (scRNA seq) at chronic timepoints in a mouse model of neonatal arterial ischemic stroke. Mice underwent 60 min of transient right middle cerebral artery occlusion (MCAO) on postnatal day 10 (p10) and received 5-ethynyl-2'-deoxyuridine (EdU) on post-MCAO days 3-7 to label dividing cells. Animals were sacrificed 14 and 28-30 days post-MCAO for immunohistochemistry and electron microscopy. Oligodendrocytes were isolated from striatum 14 days post-MCAO for scRNA seq and differential gene expression analysis. The density of Olig2+ EdU+ cells was significantly increased in ipsilateral striatum 14 days post-MCAO and the majority of oligodendrocytes were immature. Density of Olig2+ EdU+ cells declined significantly between 14 and 28 days post-MCAO without a concurrent increase in mature Olig2+ EdU+ cells. By 28 days post-MCAO there were significantly fewer myelinated axons in ipsilateral striatum. scRNA seq identified a cluster of "disease associated oligodendrocytes (DOLs)" specific to the ischemic striatum, with increased expression of MHC class I genes. Gene ontology analysis suggested decreased enrichment of pathways involved in myelin production in the reactive cluster. Oligodendrocytes proliferate 3-7 days post-MCAO and persist at 14 days, but fail to mature by 28 days. MCAO induces a subset of oligodendrocytes with reactive phenotype, which may be a therapeutic target to promote white matter repair.

Incidence and Outcome of Severe and Nonsevere Thrombocytopenia Associated With Zika Virus Infection-Puerto Rico, 2016.

BACKGROUND: Zika virus (ZIKV) infection has been associated with severe thrombocytopenia. We describe the incidence, clinical manifestations, and outcomes of patients with ZIKV infection and thrombocytopenia. METHODS: We reviewed medical records of patients with ZIKV infection and thrombocytopenia (platelet count <100 ×109 cells/L) in Puerto Rico during 2016. Severe thrombocytopenia was defined by platelet count <20 ×109/L or a platelet count <50 ×109/L and treatment for immune thrombocytopenia (ITP). RESULTS: Of 37 878 patients with ZIKV infection, 47 (0.1%) had thrombocytopenia in the absence of an alternative etiology (1.4 cases/100 000 population), including 12 with severe thrombocytopenia. Most patients with thrombocytopenia were adult (77%) and male (53%). Platelet nadir occurred a median (range) of 6 (1-16) and 5 (0-34) days after symptom onset for patients with severe and nonsevere thrombocytopenia, respectively. Among patients with severe thrombocytopenia, all had bleeding, 33% were admitted to the intensive care unit, and 8% died; 50% were treated for ITP. Among 5 patients with severe thrombocytopenia who received intravenous immunoglobulin, the median platelet count increase (range) was 112 (65-202) ×109/L. In contrast, among 4 patients who received platelet transfusion, the median increase in platelet count (range) was 8.5 (-6 to 52) ×109/L. CONCLUSIONS: Patients with severe thrombocytopenia and ZIKV infection experienced prominent acute morbidity. Consistent with recommended management, administration of ITP treatments to such patients may be more efficacious than platelet transfusion in resolving thrombocytopenia. Severe thrombocytopenia should be considered a rare outcome of ZIKV infection.

Clinical Features of Guillain-Barré Syndrome With vs Without Zika Virus Infection, Puerto Rico, 2016.

Importance: The pathophysiologic mechanisms of Guillain-Barré syndrome (GBS) associated with Zika virus (ZIKV) infection may be indicated by differences in clinical features. Objective: To identify specific clinical features of GBS associated with ZIKV infection. Design, Setting, and Participants: During the ZIKV epidemic in Puerto Rico, prospective and retrospective strategies were used to identify patients with GBS who had neurologic illness onset in 2016 and were hospitalized at all 57 nonspecialized hospitals and 2 rehabilitation centers in Puerto Rico. Guillain-Barré syndrome diagnosis was confirmed via medical record review using the Brighton Collaboration criteria. Specimens (serum, urine, cerebrospinal fluid, and saliva) from patients with GBS were tested for evidence of ZIKV infection by real-time reverse transcriptase-polymerase chain reaction; serum and cerebrospinal fluid were also tested by IgM enzyme-linked immunosorbent assay. In this analysis of public health surveillance data, a total of 123 confirmed GBS cases were identified, of which 107 had specimens submitted for testing; there were 71 patients with and 36 patients without evidence of ZIKV infection. Follow-up telephone interviews with patients were conducted 6 months after neurologic illness onset; 60 patients with and 27 patients without evidence of ZIKV infection participated. Main Outcomes and Measures: Acute and long-term clinical characteristics of GBS associated with ZIKV infection. Results: Of 123 patients with confirmed GBS, the median age was 54 years (age range, 4-88 years), and 68 patients (55.3%) were male. The following clinical features were more frequent among patients with GBS and evidence of ZIKV infection compared with patients with GBS without evidence of ZIKV infection: facial weakness (44 [62.0%] vs 10 [27.8%]; P < .001), dysphagia (38 [53.5%] vs 9 [25.0%]; P = .005), shortness of breath (33 [46.5%] vs 9 [25.0%]; P = .03), facial paresthesia (13 [18.3%] vs 1 [2.8%]; P = .03), elevated levels of protein in cerebrospinal fluid (49 [94.2%] vs 23 [71.9%]; P = .008), admission to the intensive care unit (47 [66.2%] vs 16 [44.4%]; P = .03), and required mechanical ventilation (22 [31.0%] vs 4 [11.1%]; P = .02). Six months after neurologic illness onset, patients with GBS and evidence of ZIKV infection more frequently reported having excessive or inadequate tearing (30 [53.6%] vs 6 [26.1%]; P = .03), difficulty drinking from a cup (10 [17.9%] vs 0; P = .03), and self-reported substantial pain (15 [27.3%] vs 1 [4.3%]; P = .03). Conclusions and Relevance: In this study, GBS associated with ZIKV infection was found to have higher morbidity during the acute phase and more frequent cranial neuropathy during acute neuropathy and 6 months afterward. Results indicate GBS pathophysiologic mechanisms that may be more common after ZIKV infection.

Indicadores microbianos en aguas recreativas del departamento capital de Misiones y su relación con enfermedades hídricas notificadas / Microbial indicators in recreational waters of the capital department of Misiones and their relationship with reported water diseases

INTRODUCCIÓN Se han descripto los peligros asociados con el uso recreacional de aguas en ambientes antropogénicos, sin embargo en el contexto local aún no se han realizado estudios. OBJETIVO Relacionar la calidad microbiológica de aguas recreativas del departamento Capital de Misiones y los casos clínicos notificados al sistema público. MÉTODOS Se determinaron parásitos patógenos, coliformes totales (CT), coliformes fecales (CF), enterococos (EC) y E. coli durante 45 semanas en cinco estaciones de muestreo habilitadas, y se relevaron datos de enfermedades notificadas durante 2018. RESULTADOS Se encontró (en NMP/100 ml); CT 1588,8 +/- 480,3; CF 729,1 +/- 280,2; E. coli 241,0 +/- 179,5 y EC 39,6 +/- 12,9. La recuperación de parásitos fue de 0,04 %. Sólo dos balnearios resultaron satisfactorios en el 100 % de los muestreos, mientras que el resto lo fueron en un 84%, 80% y 64%. Del 100% de los parámetros que estuvieron fuera del límite 15% fueron CT, 23% fueron E. coli, 31% fueron CF y también EC. Los niños de 2 a 4 años fueron los principales afectados por patologías de origen hídrico. Las infecciones intestinales bacilares y bacterianas (58%) y las diarreas y gastroenteritis de presunto origen infeccioso (35%) fueron las más notificadas. Hubo un mayor porcentaje de patologías asociadas a causas hídricas durante noviembre y octubre, lo que coincidió con recuentos de CF, EC y E. coli alterados. DISCUSIÓN La baja sensibilidad para determinar parásitos se debió al pequeño volumen de agua utilizado para realizar las filtraciones. Los recuentos elevados podrían haber sido causantes de algunas de las enfermedades halladas en noviembre, teniendo en cuenta que las altas temperaturas condicionan un mayor contacto con los recursos hídricos. Se requieren estudios epidemiológicos interdisciplinarios que permitan relacionar de manera fehaciente la incidencia de la calidad sanitaria de las aguas sobre la población que las utiliza

Autonomous CaMKII Activity as a Drug Target for Histological and Functional Neuroprotection after Resuscitation from Cardiac Arrest.

The Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a major mediator of physiological glutamate signaling, but its role in pathological glutamate signaling (excitotoxicity) remains less clear, with indications for both neuro-toxic and neuro-protective functions. Here, the role of CaMKII in ischemic injury is assessed utilizing our mouse model of cardiac arrest and cardiopulmonary resuscitation (CA/CPR). CaMKII inhibition (with tatCN21 or tatCN19o) at clinically relevant time points (30 min after resuscitation) greatly reduces neuronal injury. Importantly, CaMKII inhibition also works in combination with mild hypothermia, the current standard of care. The relevant drug target is specifically Ca2+-independent "autonomous" CaMKII activity generated by T286 autophosphorylation, as indicated by substantial reduction in injury in autonomy-incompetent T286A mutant mice. In addition to reducing cell death, tatCN19o also protects the surviving neurons from functional plasticity impairments and prevents behavioral learning deficits, even at extremely low doses (0.01 mg/kg), further highlighting the clinical potential of our findings.

Incidence of Zika Virus Disease by Age and Sex - Puerto Rico, November 1, 2015-October 20, 2016.

Zika virus is a flavivirus transmitted primarily by Aedes species mosquitoes; symptoms of infection include rash, arthralgia, fever, and conjunctivitis.*,† Zika virus infection during pregnancy can cause microcephaly and other serious brain anomalies (1), and in rare cases, Zika virus infection has been associated with Guillain-Barré syndrome (2) and severe thrombocytopenia (3). This report describes the incidence of reported symptomatic Zika virus disease in the U.S. territory of Puerto Rico by age and sex. During November 1, 2015-October 20, 2016, 62,500 suspected Zika virus disease cases were reported to the Puerto Rico Department of Health (PRDH); 29,345 (47%) were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) testing, or were presumptively diagnosed based on serological testing. The highest incidence among confirmed or presumptive cases occurred among persons aged 20-29 years (1,150 cases per 100,000 residents). Among 28,219 (96.2%) nonpregnant patients with confirmed or presumptive Zika virus disease, incidence was higher among women (936 per 100,000 population) than men (576 per 100,000) for all age groups ≥20 years, and the majority (61%) of reported Zika virus disease cases occurred in females. Among suspected Zika virus disease cases in nonpregnant adults aged ≥40 years, the percentage that tested positive among females (52%) was higher than that among males (47%) (p<0.01). Reasons for the higher incidence of Zika virus disease among women aged ≥20 years are not known; serosurveys of persons living near confirmed Zika virus disease cases might help to elucidate these findings. Residents of and travelers to Puerto Rico should remove or cover standing water, practice mosquito abatement, employ mosquito bite avoidance behaviors, take precautions to reduce the risk for sexual transmission, and seek medical care for any acute illness with rash or fever.

Guillain-Barré Syndrome During Ongoing Zika Virus Transmission - Puerto Rico, January 1-July 31, 2016.

Guillain-Barré syndrome (GBS) is a postinfectious autoimmune disorder characterized by bilateral flaccid limb weakness attributable to peripheral nerve damage (1). Increased GBS incidence has been reported in countries with local transmission of Zika virus, a flavivirus transmitted primarily by certain Aedes species mosquitoes (2). In Puerto Rico, three arthropod-borne viruses (arboviruses) are currently circulating: Zika, dengue, and chikungunya. The first locally acquired Zika virus infection in Puerto Rico was reported in December 2015 (3). In February 2016, the Puerto Rico Department of Health (PRDH), with assistance from CDC, implemented the GBS Passive Surveillance System (GBPSS) to identify new cases of suspected GBS (4). Fifty-six suspected cases of GBS with onset of neurologic signs during January 1-July 31, 2016, were identified. Thirty-four (61%) patients had evidence of Zika virus or flavivirus infection; the median age of these patients was 55 years (range = 21-88 years), and 20 (59%) patients were female. These 34 patients were residents of seven of eight PRDH public health regions. All 34 patients were hospitalized and treated with intravenous immunoglobulin G (IVIg), the standard treatment for GBS; 21 (62%) required intensive care unit admission, including 12 (35%) who required endotracheal intubation and mechanical ventilation. One patient died of septic shock after treatment for GBS. Additionally, 26 cases of neurologic conditions other than GBS were reported through GBPSS, including seven (27%) in patients with evidence of Zika virus or flavivirus infection. Residents of and travelers to Puerto Rico and countries with active Zika virus transmission should follow recommendations for prevention of Zika virus infections.* Persons with signs or symptoms consistent with GBS should promptly seek medical attention. Health care providers in areas with ongoing local transmission seeing patients with neurologic illnesses should consider GBS and report suspected cases to public health authorities.

Update: Ongoing Zika Virus Transmission - Puerto Rico, November 1, 2015-July 7, 2016.

Zika virus is a flavivirus transmitted primarily by Aedes aegypti and Aedes albopictus mosquitoes, and infection can be asymptomatic or result in an acute febrile illness with rash (1). Zika virus infection during pregnancy is a cause of microcephaly and other severe birth defects (2). Infection has also been associated with Guillain-Barré syndrome (GBS) (3) and severe thrombocytopenia (4,5). In December 2015, the Puerto Rico Department of Health (PRDH) reported the first locally acquired case of Zika virus infection. This report provides an update to the epidemiology of and public health response to ongoing Zika virus transmission in Puerto Rico (6,7). A confirmed case of Zika virus infection is defined as a positive result for Zika virus testing by reverse transcription-polymerase chain reaction (RT-PCR) for Zika virus in a blood or urine specimen. A presumptive case is defined as a positive result by Zika virus immunoglobulin M (IgM) enzyme-linked immunosorbent assay (MAC-ELISA)* and a negative result by dengue virus IgM ELISA, or a positive test result by Zika IgM MAC-ELISA in a pregnant woman. An unspecified flavivirus case is defined as positive or equivocal results for both Zika and dengue virus by IgM ELISA. During November 1, 2015-July 7, 2016, a total of 23,487 persons were evaluated by PRDH and CDC Dengue Branch for Zika virus infection, including asymptomatic pregnant women and persons with signs or symptoms consistent with Zika virus disease or suspected GBS; 5,582 (24%) confirmed and presumptive Zika virus cases were identified. Persons with Zika virus infection were residents of 77 (99%) of Puerto Rico's 78 municipalities. During 2016, the percentage of positive Zika virus infection cases among symptomatic males and nonpregnant females who were tested increased from 14% in February to 64% in June. Among 9,343 pregnant women tested, 672 had confirmed or presumptive Zika virus infection, including 441 (66%) symptomatic women and 231 (34%) asymptomatic women. One patient died after developing severe thrombocytopenia (4). Evidence of Zika virus infection or recent unspecified flavivirus infection was detected in 21 patients with confirmed GBS. The widespread outbreak and accelerating increase in the number of cases in Puerto Rico warrants intensified vector control and personal protective behaviors to prevent new infections, particularly among pregnant women.

Update: Ongoing Zika Virus Transmission - Puerto Rico, November 1, 2015-April 14, 2016.

Zika virus is a flavivirus transmitted primarily by Aedes species mosquitoes, and symptoms of infection can include rash, fever, arthralgia, and conjunctivitis (1).* Zika virus infection during pregnancy is a cause of microcephaly and other severe brain defects (2). Infection has also been associated with Guillain-Barré syndrome (3). In December 2015, Puerto Rico became the first U.S. jurisdiction to report local transmission of Zika virus, with the index patient reporting symptom onset on November 23, 2015 (4). This report provides an update to the epidemiology of and public health response to ongoing Zika virus transmission in Puerto Rico. During November 1, 2015-April 14, 2016, a total of 6,157 specimens from suspected Zika virus-infected patients were evaluated by the Puerto Rico Department of Health (PRDH) and CDC Dengue Branch (which is located in San Juan, Puerto Rico), and 683 (11%) had laboratory evidence of current or recent Zika virus infection by one or more tests: reverse transcription-polymerase chain reaction (RT-PCR) or immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA). Zika virus-infected patients resided in 50 (64%) of 78 municipalities in Puerto Rico. Median age was 34 years (range = 35 days-89 years). The most frequently reported signs and symptoms were rash (74%), myalgia (68%), headache (63%), fever (63%), and arthralgia (63%). There were 65 (10%) symptomatic pregnant women who tested positive by RT-PCR or IgM ELISA. A total of 17 (2%) patients required hospitalization, including 5 (1%) patients with suspected Guillain-Barré syndrome. One (<1%) patient died after developing severe thrombocytopenia. The public health response to the outbreak has included increased laboratory capacity to test for Zika virus infection (including blood donor screening), implementation of enhanced surveillance systems, and prevention activities focused on pregnant women. Vector control activities include indoor and outdoor residual spraying and reduction of mosquito breeding environments focused around pregnant women's homes. Residents of and travelers to Puerto Rico should continue to employ mosquito bite avoidance behaviors, take precautions to reduce the risk for sexual transmission (5), and seek medical care for any acute illness with rash or fever.

Sex differences in the effect of childhood trauma on the clinical expression of early psychosis.

Childhood trauma, a risk factor of psychosis, is associated the clinical expression of the illness (greater severity of psychotic symptoms; poorer cognitive performance). We aimed to explore whether there are sex differences in this relationship. We studied 79 individuals with a psychotic disorder (PD) with <3years of illness and 59 healthy subjects (HS). All participants were administered the MATRICS Cognitive Consensus Cognitive Battery (MCCB) to assess cognition. Depressive, positive and negative psychotic symptoms, and global functioning were also assessed. History of childhood trauma was assessed using the Childhood Trauma Questionnaire (CTQ). Patients reported a greater history of childhood trauma on all CTQ domains (emotional, physical and sexual abuse, and physical and emotional neglect). A poorer cognitive performance was also observed in PD when compared to HS. No sex differences were found in the CTQ scores. In the relationship between childhood trauma and psychopathological symptoms, significant correlations were found between CTQ scores and positive and negative psychotic symptoms, depressive symptoms and poorer functionality, but only in women. Childhood trauma was associated with poorer social cognition in both men and women. Of all CTQ dimensions, emotional neglect and physical neglect were more clearly associated with a more severe psychopathological and cognitive profile. Our results suggest that childhood trauma, particularly emotional and physical neglect, is associated with the clinical expression of psychosis and that there are sex differences in this relationship.

Susceptibilities to carbapenems and presence of cphA gene on food-borne Aeromonas

The purpose of this study was to determine the susceptibilities of food-borne Aeromonas to carbapenems, as well as to investigate the presence of a metallo carbapenemase-encoding gene, named cphA. Minimum Inhibitory Concentration (MIC) was determined following NCCLS standards. All the tested microorganisms were susceptible to imipenem, meropenem and biapenem. However, a strong inoculum size effect on carbapenem MICs was observed for most of the strains. Six strains, out of seven, showed the presence of metallo--beta-lactamases but cphA gene was detected in only two strains of A. veronii bv. sobria.

O objetivo deste estudo foi determinar a suscetibilidade de aeromonas de origem alimentar a carbapenems bem como investigar a presença de um gene codificante de metalocarbapenemase, denominado "cph A". A suscetibilidade in vitro foi determinada pelo metodo de diluição em agar. Todas as cepas foram suscetíveis a Imipenem, Meropenem e Biapenem. Porém foi observado um forte efeito de tamanho do inóculo sobre as CIM das carbapenems na maioria das cepas. A detecção de metalo-beta-lactamase foi realizada pelo metodo lodometrico. Seis cepas das sete testadas demostraron a presença da enzima. A presença do gene cphA foi determinada por PCR e foi detectada em duas cepas de A veronii bv. sobria.

Prevalencia y causas de abandono de lactancia materna en el alojamiento conjunto de una institución de tercer nivel de atención / The impact of rooming-in at the hospital on the prevalence and causes of abandonment of beast feeding

Introducción. La leche materna es la mejor alimentación para neonatos y lactantes. México tiene una tasa de lactancia exclusiva de 33.6%. Objetivo. Conocer la prevalencia de lactancia materna e identificar factores que favorecen su práctica y abandono. Material y métodos. Estudio prospectivo, de cohorte, analítico, en binomios madre-hijo con seguimiento de 6 meses. Se investigó: tipo de alimentación, motivos de abandono de lactancia materna exclusiva. Se aplicaron medidas de tendencia central: X², prueba exacta de Fisher y t de Student. Resultados. Completaron seguimiento 111; 75 (67.6%) con lactancia materna exclusiva, 32 (28.8%) con lactancia mixta, y 4 (3.6%) con sucedáneos. En el grupo con escolaridad de 0 a 6 años se encontró un riesgo relativo de 1.29, intervalo de confianza de 1.09, 1.84, P =0.11 (prueba exacta de Fisher). Conclusiones. Prevalencia de lactancia materna exclusiva: 67.6%. Causa de abandono: producción baja. Única variable significativa para lactar exclusivamente al seno materno y permanecer en el seguimiento: escolaridad 0 a 6 años.

Introduction. Breast milk is the best feeding source for newborns and infants. Mexico has a 33.6% rate of exclusively breastfeeding. Objective: to evaluate the impact of rooming in on the prevalence of breastfeeding and identify the elements that encourage its practice and abandonment. Material and methods. Prospective, cohort, analytical, study in mother-infant pair study with a 6 month follow-up. We analyzed the type of feeding, reasons for changing or abandoning breastfeeding; we applied: central tendency measurements, %², Fisher's exact and t of Student. Results. In 111 completed follow-up, 75 infants (67.6%) remained exclusively on breast milk, 32 (28.8%) mixed feeding and 4 (3.6%) with proprietary formulas. In the group with 0 to 6 years of schooling we found a RR: 1.29, IC: 1.01, 1.64, P =0.11 [Fisher's exact]. Conclusions. Prevalence of exclusive breastfeeding: 67.6%. Cause of abandonment: low milk production. The only significant variable, for lactating breast milk exclusively and remain in the follow-up was schooling 0 to 6 years.

Transmission of T. cruzi infection via liver transplantation to a nonreactive recipient for Chagas' disease.

Chagas' disease is an endemic zoonosis of South America caused by a protozoan parasite Trypanosoma cruzi. About 30% of infected people develop the disease. This disease is known to reactivate in immunocompromised hosts, such as patients with acquired immunodeficiency syndrome, leukemia, and transplantation. There is some experience with transplantation of infected renal grafts into negative recipients, resulting in an index of transmission of 35%. No cases have been reported involving other organ transplants up to 2002, when the Centers for Disease Control and Prevention reported 3 cases of Chagas' disease transmission to 3 recipients (liver, kidney, and pancreas-kidney) from a single chagas infected donor. Here we report on a case of orthotopic liver transplant from a chagas infected donor into a negative recipient in clinical emergency status. The recipient was monitored by direct parasitological Strout method and serological tests with detection of transmission on the 84 th day by both studies, without clinical signs. The patient was put on benznidazole with rapid clearance of the parasitemia. However, we propose that chagas infected donors may be accepted for liver transplant recipients only in emergency status.

Abnormal immunological response to Mycobacterium tuberculosis antigens in a patient with chronic myelocytic leukemia and active tuberculosis

The pathogenic mechanisms of immunosuppression leading to susceptibility of Mycobacterium tuberculosis (MT) infection in chronic myelocytic leukemia (CML) are not clear. To address this issue, we measured the proliferative response, variation of T cell subpopulations (CD4+, CD8+, TCR-V delta 2 and TCR-V beta 8 T cells) and the cytokine profile (IL-1 beta, IL-2, IL-4, IL-6, IL-10, TNF-alpha, IFN-gamma) after MT stimulation of peripheral blood mononuclear cells (PBMC) in a patient with concomitant CML and active pulmonary tuberculosis. The results were compared to four patients with active pulmonary tuberculosis and no other coexistent diseases. The immunologic response to phytohemagglutinin (PHA) was also evaluated. In contrast to controls, the CML PBMC failed to proliferate in response to MT antigens. Mycobacterium-reactive CD4+, V delta 2 and V beta 8 T cells did not expand after MT stimulation of the CML PBMC. In MT antigens-stimulated cultures from the CML patient, IL-2 was not produced and mild reduction of IL-1 beta and INF-gamma were observed. In contrast, IL-10 was markedly elevated in these cultures. Similarly, PHA-stimulated PBMC from the CML patient showed no expansion of CD4+ and CD8+. T cells. In these cell cultures, INF-gamma concentration in supernatants was decreased and IL-10 was significantly elevated. This study suggests that patients with CML may present a profound immunosuppression of essential cellular and molecular immune effectors, a scenario which might contribute to the development of active tuberculosis. These findings further support the need of establishing immunotherapeutic modalities with potential value for myeloproliferative disorders.