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Biomedical subjects

Stanley G Cron

Publications and source records attributed to Stanley G Cron.

8 recordsLinked to original sources
PubMed2007

Human metapneumovirus and respiratory syncytial virus infections in older children with cystic fibrosis.

BACKGROUND: Human metapneumovirus (hMPV) has been isolated from children with acute respiratory infection worldwide. Its epidemiology remains to be defined in children with cystic fibrosis (CF). We describe the epidemiology and clinical impact of hMPV in CF children and compared it to respiratory syncytial virus (RSV). METHODS: CF children ages 7-18 years were studied prospectively during the 1998 -1999 RSV season. Nasopharyngeal specimens were collected during acute respiratory illnesses and tested for respiratory viruses. Blood specimens were drawn early, mid, and end of the RSV season, and tested for serological evidence of hMPV and RSV infections. Rates of lower respiratory tract illnesses (LRTI) and hospitalizations for pulmonary exacerbations were compared during the time intervals they developed serological evidence of infection to their non-infection intervals. RESULTS: Six of 44 CF children had a virus positive respiratory illness in 56 LTRI events and 18 hospitalizations. Serological evidence of hMPV and RSV infections occurred in 16 and 20 CF children, respectively; 8 had infections with both viruses. A greater proportion of CF children had >or=1 LRTI during their infection intervals compared to their non-infection intervals (13/25 vs. 5/25; P=0.03). A trend for higher rates of LRTI was observed in the infection intervals compared to non-infection intervals (9.5 +/- 11.0 vs. 4.2 +/- 9.9 per 1,000 child-days; P=0.06), and it was significantly greater with a more conservative estimate (one event per child per interval; 7.4 +/- 7.7 vs. 2.6 +/- 5.4 per 1,000 child-days; P <or=0.01). No differences in hospitalizations rates were detected. CONCLUSION: The infection rates and clinical impact observed for hMPV were comparable to that for RSV in CF children 7-18 years of age.

Adolescent↗
PubMed2005

Neonates with aortic coarctation and cardiogenic shock: presentation and outcomes.

BACKGROUND: Some neonates with coarctation of the aorta (COA) present with cardiogenic shock and secondary end-organ injury. The management of this subgroup imposes unique challenges. We review our perioperative strategy and outcomes for neonates with COA who presented with cardiogenic shock. METHODS: Neonates (younger than 30 days) with isolated COA or COA with aortic arch hypoplasia were identified. Retrospective review was performed to identify and characterize patients who presented with cardiogenic shock, defined as impaired left ventricular (LV) or right ventricular (RV) systolic function, or both, respiratory failure requiring tracheal intubation, and metabolic acidosis. RESULTS: Thirteen neonates presented in cardiogenic shock and underwent surgical repair. No patients required catheter or surgical reintervention for recoarctation. There were no deaths at a mean follow-up of 54 months. Group I neonates (isolated COA, n = 7) underwent end-to-end anastomosis through left thoracotomy. The mean age and pH at presentation were 9 (+/-1.1) days and 7.07 (+/-0.21), respectively. The mean preoperative and postoperative LV myocardial performance indices (MPI) were 0.81 (+/-0.22) and 0.37 (+/-0.16), respectively (p = 0.002). Group II neonates (COA with arch hypoplasia +/- ventricular septal defect, n = 6) underwent aortic arch advancement and ventricular septal defect closure through median sternotomy. The mean time from diagnosis to surgery in group II was 5.5 (+/-1.9) days versus 2.4 (+/-1.5) days in group 1 (p = 0.01). The mean age and pH at presentation were 11.8 (+/-9.3) days and 7.02 (+/-0.21), respectively. The mean preoperative and postoperative LV MPI were 0.46 (+/-0.13) and 0.35 (+/-0.11), respectively (p = 0.02). The total hospital length of stay in group II patients was 18 (+/-6.23) days versus 11.3 (+/-5. 7) days in group I (p = 0.04). CONCLUSIONS: Timely intervention with a strategy individualized to the patient anatomy can be performed with excellent outcomes in neonates with COA and cardiogenic shock. Neonates with isolated COA had worse preoperative LV MPI, which reflects more significant global left ventricular systolic dysfunction in this subgroup. The elapsed time from diagnosis to surgery was decreased in neonates with isolated COA.

Aortic Coarctation↗
PubMed2005

Longitudinal study of the prevalence and prognostic implications of oral manifestations in romanian children infected with human immunodeficiency virus type 1.

OBJECTIVE: We evaluated the prevalence and predictive value for human immunodeficiency virus (HIV) disease progression of oral manifestations in Romanian children. METHODS: A nonrandom sample of 238 HIV-infected children was followed prospectively between 1998 and 2001 at the Romanian-American Children's Center in Constanta, Romania. Study subjects underwent comprehensive annual oral examinations. Oral manifestations of interest, demographic data and other selected medical information were recorded at baseline and at each subsequent visit. Descriptive statistics and survival analysis methods were used in the study. A level of statistical significance of alpha = 0.05 was used. RESULTS: The study subjects' mean age was 9.9 +/- 1.2 (SD) years. The most common oral lesions were gingivitis (49%), parotid enlargement (13%) and oral candidiasis (11%). Oral candidiasis was associated with progression to acquired immunodeficiency syndrome or death (whichever occurred first) (log rank P = 0.03) and with death (log rank P < 0.001). Oral hairy leukoplakia also was associated with progression to death (log rank P = 0.001). The risk of dying was 3.43 (95% confidence interval, 1.86-6.34; P < 0.001) for children who had oral candidiasis at baseline and 4.62 (95% confidence interval, 1.67-12.77; P = 0.003) for those who had oral hairy leukoplakia. CONCLUSIONS: Oral manifestations occur commonly among HIV-infected Romanian children. Oral candidiasis and oral hairy leukoplakia were positive predictors of HIV disease progression.

AIDS-Related Opportunistic Infections↗
PubMed2003

Correlates of immunity to respiratory syncytial virus (RSV) associated-hospitalization: establishment of minimum protective threshold levels of serum neutralizing antibodies.

OBJECTIVE: To determine if respiratory syncytial virus (RSV) specific, serum antibody titers correlate with protection against RSV associated-hospitalization at all ages. DESIGN: Participants who were enrolled in a trial to determine the frequency of specific virus infections associated with hospitalization [J. Am. Med. Assoc. 283 (2000) 499] were included in our analysis if they were enrolled from July 1991 to June 1993, had a culture for virus isolation, and provided blood samples at hospitalization and 14-60 days later. RSV infection was defined by a positive culture and/or serology. Microneutralization, ELISA to the fusion (F) protein and Western blot were the serological assays that were used to determine correlates of immunity. RESULTS: One hundred and seventy-five individuals, 1 month to 89 years old, out of 538 patients hospitalized with an acute respiratory infection met the criteria for analysis. RSV associated-hospitalization occurred in 11 (40.7%) of 27 infants (<1 year), 8 (38.1%) of 21 young children (1 to <5 years), and 15 (11.8%) of 127 children and adults (> or =5 years). At the time of hospitalization, geometric mean neutralizing antibody titers (log(2)) to RSV/A and RSV/B, and geometric mean binding antibody titer (log(2)) to F protein were significantly higher in patients with non-RSV associated-hospitalization compared to those with RSV associated-hospitalization (RSV/A: 7.9 versus 6.1, P<0.001; RSV/B: 9.4 versus 7.3, P<0.001; ELISA-F, 13.9 versus 12.6, P=0.01). For every 1 log(2) increase in titer of neutralizing antibodies to RSV/A and RSV/B, and binding antibody to F protein there was a significant increase in the likelihood of not having an RSV associated-hospitalization by 22.3, 25, and 24.4% respectively. A minimal protective threshold titer of > or =6.0 (odds ratio 3.5; 95% CI 1.4-9.1) and > or =8.0 log(2) (odds ratio 2.9; 95% CI 1.1-7.7) against RSV associated-hospitalization was established for neutralizing antibodies to RSV/A and RSV/B; a threshold titer could not be established for binding antibody to F protein. CONCLUSION: Participants with naturally acquired serum neutralizing antibody levels at least equal to the minimal protective threshold titer were approximately three times more likely not to have an RSV associated-hospitalization. We speculate that achieving a minimal protective threshold antibody titer through active immunization will significantly reduce RSV associated-hospitalization among all ages.

Adolescent↗
PubMed2003

Immunogenicity of a new purified fusion protein vaccine to respiratory syncytial virus: a multi-center trial in children with cystic fibrosis.

A third generation, purified fusion protein (PFP-3) vaccine was developed to prevent severe respiratory syncytial virus (RSV) disease in high-risk groups. A phase II, multi-center, adjuvant-controlled trial was performed in RSV seropositive children with cystic fibrosis (CF); 151 received the adjuvant-control and 143 received the vaccine. Details of the vaccine-induced immune response are presented. At enrollment, RSV-specific, serum antibodies were comparable between both groups. A highly sensitive and specific serum antibody vaccine profile was established for the PFP-3 vaccine. At post-vaccination and end-of-study, RSV-specific, neutralizing antibody (Nt Ab) and binding antibody (Bd Ab) to the fusion (F) protein were significantly higher in PFP-3 vaccinees. After 28 days post-vaccination, Nt Ab and Bd Ab to F protein titers declined slowly at rates of 0.23 and 0.37 log2 per month, respectively. The PFP-3 vaccine-induced a robust immune response that lasted throughout the RSV season.

Adjuvants, Immunologic↗
PubMed2002

Suppression of human anti-inflammatory plasma cytokines IL-10 and IL-1RA with elevation of proinflammatory cytokine IFN-gamma during the isolation of the Antarctic winter.

Cellular immune function has been shown to be decreased and latent virus shedding to be increased in human beings isolated during the Antarctic winter, a model used for assessing some effects of space flight. However, the balance of proinflammatory (IFN-gamma) and anti-inflammatory (IL-10 and IL-1RA) cytokines has not previously been evaluated. We therefore sought to determine whether isolation during the Antarctic winter would alter the proinflammatory and anti-inflammatory cytokine balance. Cytokine levels were measured with ELISA in monthly plasma samples from January through September 1999 in 21 study subjects in the Antarctic and 7 control subjects on Macquarie Island. There was a significant time-dependent increase in plasma IFN-gamma (P =.039) as well as decreases in IL-10 (P =.042) and IL-1RA (P =.053) in the study subjects compared with the control subjects. The study subjects also had significantly increased plasma IFN-gamma levels (P < or =.045) but decreased IL-10 and IL-1RA levels (P < or =.036) at individual time points of isolation. Isolation of human beings in the Antarctic appears to shift the plasma cytokine balance toward a proinflammatory profile. These observations are consistent with T-cell activation that might be due to activation of latent viruses, and they could hold importance for determining the risks of space flight.

Antarctic Regions↗
PubMed2002

Magnitude of IFN-gamma production in HIV-1-infected children is associated with virus suppression.

BACKGROUND: Little is known about the cytokine production by peripheral blood cells of pediatric patients who have suppressed HIV-1 replication after highly active antiretroviral therapy (HAART). OBJECTIVE: We sought to determine the effect of HAART on the production of T(H)1 and T(H)2 cytokines by HIV-infected children who have suppressed HIV replication. METHODS: At 3- to 6-month intervals over a 5-year period, CD4(+) T cells were enumerated, plasma HIV-1 RNA was measured, and levels of cytokine production by whole blood cultures were determined in 21 HIV-1-infected children. RESULTS: Ten patients achieved an HIV-1 RNA level of less than 3000 copies/mL of plasma and maintained that level for at least 15 months (virus-suppressed [VS] group). Eleven patients had a mean HIV-1 RNA level of greater than 10(4) copies/mL of plasma and a mean CD4(+) T-cell count of less than 500/microL of blood (active infection group). The median levels of anti-CD3-induced IL-2, IFN-gamma, and IL-10 in the active infection group were significantly lower than those in the VS group after suppression of the virus. The median slope of IFN-gamma production by means of PHA-stimulated culture after achieving VS status (4.04) was significantly higher than the level before VS status (-1.31, P =.004). The difference in the median slopes for IL-10 production by anti-CD3-stimulated cultures before (0.21) and after (-0.16) achieving VS status was statistically different (P =.027). CONCLUSION: The immune restoration of HIV-1-infected children receiving HAART might be related to an increase in IFN-gamma production and a decrease in the rate of IL-10 production after virus suppression.

Antiretroviral Therapy, Highly Active↗