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Biomedical subjects

David Greenberg

Publications and source records attributed to David Greenberg.

At least 19 recordsLinked to original sources
PubMed2006

Adaptive changes in acetylcholinesterase gene expression as mediators of recovery from chemical and biological insults.

Both organophosphate (OP) exposure and bacterial infection notably induce short- and long-term cholinergic responses. These span the central and peripheral nervous system, neuromuscular pathway and hematopoietic cells and involve over-expression of the "readthrough" variant of acetylcholinesterase, AChE-R, and its naturally cleavable C-terminal peptide ARP. However, the causal involvement of these changes with post-exposure recovery as opposed to apoptotic events remained to be demonstrated. Here, we report the establishment of stably transfected cell lines expressing catalytically active human "synaptic" AChE-S or AChE-R which are fully viable and non-apoptotic. In addition, intraperitoneally injected synthetic mouse ARP (mARP) elevated serum AChE levels post-paraoxon exposure. Moreover, mARP treatment ameliorated post-exposure increases in corticosterone and decreases in AChE gene expression and facilitated earlier retrieval of motor activity following both paraoxon and lipopolysaccharide (LPS) exposures. Our findings suggest a potential physiological role for overproduction of AChE-R and the ARP peptide following exposure to both chemical warfare agents and bacterial LPS.

Adaptation, Physiological↗
PubMed2006

The important role of nontypable Streptococcus pneumoniae international clones in acute conjunctivitis.

BACKGROUND: In a recent epidemiological study in southern Israel, nontypable Streptococcus pneumoniae isolates were found to be highly associated with sporadic cases of acute conjunctivitis (AC). The purpose of the present study was to evaluate the relative importance in causing AC of the absence of capsule versus genotype properties. METHODS: DNA typing by pulsed-field gel electrophoresis (PFGE) was performed on 148 nontypable organisms isolated from 3 sites: nasopharynx of healthy children, middle-ear fluid, and conjunctiva. RESULTS: Analysis of the PFGE patterns revealed the presence of 6 clusters; 2 clusters that included 44% of the isolates (65/148) were associated with AC, and the remaining 4 were frequently isolated from the nasopharynx. Multilocus sequence typing, performed on representative isolates of the 2 major clusters, confirmed that the organisms were pneumococci; one is a single-locus variant of sequence type (ST) 448, and the other is related to ST344. Both types appear to be members of pneumococcal lineages that have lost capsular loci. The nontypable isolates showed high rates of resistance to antimicrobial agents. CONCLUSIONS: Our data suggest that the absence of the capsule--along with other, yet-unidentified genetic characteristics--provide S. pneumoniae with a selective virulence advantage in conjunctivitis.

Bacterial Typing Techniques↗
PubMed2006

Adult pertussis is hazardous for the newborn.

We report 4 cases involving the likely transmission of pertussis from parents to newborns in a hospital setting. The adoption of proper infection control measures and targeted screening of parents may reduce the potential for such transmission.

Adult↗
PubMed2006

Domestic water supplies as a possible source of infection with Simkania.

OBJECTIVES: Simkania negevensis, a Chlamydia-like microorganism that has been associated with respiratory infections in children and adults, can multiply within free-living amoebae; moreover, it has been detected in domestic water supplies. The aim of this study was to determine whether there is similarity between Simkania organisms found in water and those detected in clinical samples. METHODS: PCR, membrane immunoassay for the detection of Simkania antigen, and isolation in cell culture were used for the detection of S. negevensis in nasopharyngeal wash samples (NPW) of 34 children with pneumonia and in domestic water samples from their homes. Sequencing of PCR amplicons was used for comparison of Simkania strains isolated from clinical samples and from water samples. RESULTS: In 26 cases (76%) both NPW and water were positive, and partial 16S rDNA sequences suggested that they may be the same organisms. CONCLUSION: Simkania found in domestic water supplies may be transmitted to children .

Bacterial Proteins↗
PubMed2006

The contribution of smoking and exposure to tobacco smoke to Streptococcus pneumoniae and Haemophilus influenzae carriage in children and their mothers.

BACKGROUND: Exposure to tobacco smoke is associated with higher risk of Streptococcus pneumoniae and Haemophilus influenzae infection. The aim of this study was to determine the influence of smoking and exposure to tobacco smoke on S. pneumoniae and H. influenzae carriage rates in children and their mothers. PATIENTS AND METHODS: We performed a cross-sectional surveillance study of nasopharyngeal and oropharyngeal carriage of S. pneumoniae and H. influenzae in 208 children aged <60 months and their mothers. Smoking exposure and medical history were recorded. Carriage rates for children and their mothers in nasopharyngeal and oropharyngeal specimens were analyzed on the basis of smoking exposure. RESULTS: The S. pneumoniae carriage rate was higher among children exposed to smoking than among nonexposed children (76% vs. 60%; P=.016). Exposed children more frequently carried S. pneumoniae serotypes included in the conjugate 7-valent vaccine, compared with nonexposed children (49% vs. 30% of all S. pneumoniae-positive nasopharyngeal cultures; P=.02). Carriage rates of S. pneumoniae were higher among mothers who smoked than among mothers exposed to smoking and among nonexposed mothers (32%, 15%, and 12%, respectively; P=.03). There were no differences in H. influenzae carriage rates between children and mothers from smoking and nonsmoking families. CONCLUSIONS: Exposure to tobacco smoke increased S. pneumoniae carriage rates in general and for carriage of serotypes included in the conjugate 7-valent vaccine in particular in children. Smoking mothers had a higher S. pneumoniae carriage rate than did nonsmoking mothers. Smoking or exposure to smoking did not increase H. influenzae carriage rates in children and mothers.

Adult↗
PubMed2006

Problem pathogens: paediatric legionellosis--implications for improved diagnosis.

Legionnaires' disease is an established and frequent cause of pneumonia in adults but is thought to be a rare cause in children. We reviewed the medical literature for cases of Legionnaires' disease in children and analysed the epidemiology, clinical characteristics, and treatment. 76 cases of legionella infection in children were identified. In 56%, diagnosis was made with culture methodology. 46% were community-acquired infections. 51.5% were under 2 years of age. 78% of the patients had an underlying condition such as malignancy. Fever, cough, and tachypnoea were the most common symptoms. The overall mortality rate was 33% and was higher in immunosuppressed children and in children younger than the age of 1 year. Patients who were treated empirically with anti-legionella therapy had a notably lower mortality rate compared with patients on inappropriate therapy (23%vs 70%). In 88% of hospital-acquired cases, an environmental link to potable water colonised with legionella was identified. We found no clinical features unique to Legionnaires' disease in children that would allow differentiation from pneumonia due to other respiratory pathogens. Awareness of legionella as a potential cause of paediatric pneumonia is particularly important because infection can be severe and life threatening and antimicrobial therapy often used for empirical therapy in children is not effective against legionella. In any case of pneumonia unresponsive to antibiotics, Legionnaires' disease should be considered and specific diagnostic tests to verify this diagnosis should be done. As legionella diagnostic tests become more widely applied, we predict that legionellosis may appear as an emerging infectious disease in children.

Adolescent↗
PubMed2006

Comparison of human metapneumovirus, respiratory syncytial virus and influenza A virus lower respiratory tract infections in hospitalized young children.

BACKGROUND: We compared the clinical and demographic features of children with lower respiratory tract infection (LRI) caused by human metapneumovirus (HMPV), respiratory syncytial virus (RSV) and influenza A virus and sought to determine whether coinfection by HMPV and other respiratory viruses leads to increased disease severity. METHODS: Nasal wash specimens were prospectively obtained from 516 children hospitalized for LRI during a 1-year period and tested for the presence of HMPV by reverse transcription-polymerase chain reaction and for RSV and influenza A by direct immunofluorescence. RESULTS: HMPV was detected in 68 (13%) patients and was the third most common viral pathogen; 16 of 68 HMPV-positive children (24%) had coinfection with other respiratory viruses (HMPVco).HMPV patients were older than RSV patients (17.6 +/- 16.8 months versus 10.5 +/- 11.8 months, P = 0.02). HMPV was associated with wheezing and hypoxemia at a rate similar to that of RSV and higher than that of influenza A. Atelectasis was more common among HMPV (40%) than among RSV and influenza patients (13%, P < 0.05 for each). HMPV infection was more often associated with a diagnosis of pneumonia than RSV and influenza A and was more often associated with a diagnosis of asthma and less often associated with a diagnosis of bronchiolitis than RSV infection (P < 0.05 for each), even when corrected for age. Children with HMPVco had a higher rate of gastrointestinal symptoms but did not show a more severe respiratory picture. CONCLUSIONS: The clinical pattern of HMPV more closely resembles that of RSV than that of influenza A LRI, yet the differences in age, radiographic findings and clinical diagnosis suggest that HMPV pathogenesis may differ from that of RSV.

Animals↗
PubMed2006

Site-specific disease potential of individual Streptococcus pneumoniae serotypes in pediatric invasive disease, acute otitis media and acute conjunctivitis.

BACKGROUND: Recent studies have shown that some Streptococcus pneumoniae serotypes possess a higher potential to cause invasive disease than others. However, it is unknown whether disease potential for specific serotypes is similar for mucosal disease. Our objective was to assess the disease potential of individual S. pneumoniae serotypes causing invasive pneumococcal disease (IPD), acute otitis media (AOM) and acute conjunctivitis (AC) in children. METHODS: Serotypes of pneumococcal isolates from children with IPD, AOM and AC were compared with those carried by healthy children aged <3 years. All children resided in the same area and were studied during the same period. Odds ratios for disease were calculated for each diagnosis following multivariate analysis, including gender, age, ethnic group, previous antibiotic treatment and year variability. RESULTS: A total of 5,500 isolates were collected: 189 from blood or cerebrospinal fluid, 3,200 from middle ear fluid, 348 from conjunctiva and 1,763 from nasopharynx of healthy children. A significant positive association with IPD was demonstrated for serotypes 1, 5 and 12F; with AOM for serotypes 1, 3, 5, 12F, 19A and 19F; and with AC for serotype 3 and nontypeable S. pneumoniae. A significant negative association with IPD was demonstrated for nontypeable S. pneumoniae and with AOM for serotypes 6A, 6B, 15A and nontypeable S. pneumoniae. CONCLUSIONS: Our results reflect the importance of the polysaccharide capsule in site-specific disease potential and provide useful information regarding disease potential of nonvaccine serotypes shown to be involved in carriage replacement after vaccination with the 7-valent conjugate vaccine.

Acute Disease↗
PubMed2006

Will reduction of antibiotic use reduce antibiotic resistance?: The pneumococcus paradigm.

Community-acquired respiratory infections in general, and those caused by S. pneumoniae in particular, are the main reason for prescribing antimicrobials in young children. Antibiotic drug abuse is common. This is the basis for the initiative for the reduction in antibiotic use. However, failure to consider that not all antibiotics are similar in their effect on promotion of resistance has led to continuous emerging resistance. In the present article, the trends in prescribing antibiotics in young children and their interrelation with antibiotic resistance among clinical respiratory isolates of S. pneumoniae in children will be reviewed, along with theoretical considerations and research evidence that led to concluding that among antibiotics, the least resistance-promoting drug for S. pneumoniae is amoxicillin (+/- clavulanate), whereas oral cephalosporins and azithromycin demonstrate a higher resistance-promotion potential in the individual population in the community. Although antibiotics differ in their resistant-promotion potential, all still do promote resistance.

Anti-Bacterial Agents↗
PubMed2005

Immunogenicity of an inactivated hepatitis A pediatric vaccine: three-year post-booster follow-up.

The persistence of anti-hepatitis A virus antibody concentrations was followed over 3 years in 177 healthy children following primary and booster vaccination with an inactivated hepatitis A vaccine, Avaxim 80 pediatric. Seroconversion rates (post-immunization anti-HAV antibody concentration >or=20 mIU/mL) and geometric mean concentrations (GMC) were estimated for each of three age groups: 18 month--3 years, 4--8 years, and 9--15 years. Only subjects who were initially HAV-seronegative at inclusion (<20 mIU/mL) were analyzed. Follow-up visits at years 1, 2, and 3 involved 177, 149, and 135 children, respectively. A decline in GMCs of about 74% occurred during the first year, from 3,060 to 814 mIU/mL overall, but did not continue during years 2 and 3. All subjects remained seropositive (antibody concentration >or=20 mIU/mL), with overall GMCs of 814, 891, and 924 mIU/mL in years 1--3, respectively. The inactivated hepatitis A study-vaccine resulted in sustained seroprotective antibody concentrations in 100% of these children, without a significant decline in antibiotic concentrations over the 3 years following booster injection, thus demonstrating the long-term protection expected with this vaccine.

Adolescent↗
PubMed2005

Nutritional status and diarrheal illness as independent risk factors for alveolar pneumonia.

Community-acquired alveolar pneumonia (CAAP) is typically associated with bacterial infections and is especially prevalent in vulnerable populations worldwide. The authors studied nutritional status and diarrheal history as risk factors for CAAP in Bedouin children <5 years of age living in Israel. In this prospective case-control study (2001-2002), 334 children with radiographically confirmed CAAP were compared with 529 controls without pneumonia with regard to nutritional status and diarrhea history. Controls were frequency matched to cases on age and enrollment month. Logistic regression models were used to evaluate associations of CAAP with nutritional status and recent diarrhea experience. Anemia (adjusted odds ratio (AOR) = 3.32, 95% confidence interval (CI): 2.24, 4.94; p < 0.001), low birth weight (AOR = 2.16, 95% CI: 1.32, 3.54; p = 0.002), stunting (AOR = 2.22, 95% CI: 1.31, 3.78; p = 0.004), serum retinol concentration (AOR = 1.03 per microg/dl, 95% CI: 1.02, 1.05; p < 0.001), and having > or =1 diarrhea episodes within 31 days prior to enrollment (AOR = 2.30, 95% CI: 1.26, 4.19; p = 0.007) were identified as risk factors for CAAP. Results suggest that improving antenatal care and the nutritional status of infants may reduce the risk of CAAP in Bedouin children. Furthermore, they suggest that vaccines developed to prevent diarrhea may also lower the risk of CAAP.

Anemia↗
PubMed2005

Season-of-birth as a risk factor for the seasonality of suicidal behaviour.

Despite implicating the same biological systems, the relationship between suicide seasonality and season-of-birth has not been examined previously. The purpose of this study was to investigate the interaction between season-of-birth and the seasonality of suicidal behaviour. All adult suicides (N = 2923) and deliberate self harm (DSH) hospitalizations (N = 33321) in Western Australia (1970-96) were examined. A variable population at risk approach was used to determine season-of-birth. Seasonality was established by spectral analysis. We found that DSH has a significant season-of-birth (p = 0.047) and seasonality of occurrence, both peaking in spring. Individuals born in the 90 days centred on the peak birth period, however, show no DSH seasonality. In contrast, suicide has no season-of-birth (p = 0.53). We also found a season-of-birth effect among the DSH group that eliminates any seasonality of DSH among the high-risk by birth group. Further work is needed to identify the possible biological and environmental determinants of this interaction.

Adolescent↗
PubMed2005

Imaging input and output of neocortical networks in vivo.

Neural activity manifests itself as complex spatiotemporal activation patterns in cell populations. Even for local neural circuits, a comprehensive description of network activity has been impossible so far. Here we demonstrate that two-photon calcium imaging of bulk-labeled tissue permits dissection of local input and output activities in rat neocortex in vivo. Besides astroglial and neuronal calcium transients, we found spontaneous calcium signals in the neuropil that were tightly correlated to the electrocorticogram. This optical encephalogram (OEG) is shown to represent bulk calcium signals in axonal structures, thus providing a measure of local input activity. Simultaneously, output activity in local neuronal populations could be derived from action potential-evoked calcium transients with single-spike resolution. By using these OEG and spike activity measures, we characterized spontaneous activity during cortical Up states. We found that (i) spiking activity is sparse (<0.1 Hz); (ii) on average, only approximately 10% of neurons are active during each Up state; (iii) this active subpopulation constantly changes with time; and (iv) spiking activity across the population is evenly distributed throughout the Up-state duration. Furthermore, the number of active neurons directly depended on the amplitude of the OEG, thus optically revealing an input-output function for the local network. We conclude that spontaneous activity in the neocortex is sparse and heterogeneously distributed in space and time across the neuronal population. The dissection of the various signal components in bulk-loaded tissue as demonstrated here will enable further studies of signal flow through cortical networks.

Action Potentials↗
PubMed2005

Adherence to therapeutic guidelines for acute otitis media in children younger than 2 years.

OBJECTIVES: to analyze adherence to therapeutic guidelines for AOM. METHODS: Descriptive retrospective study of community primary care providers in southern Israel. Study population (n = 590) included all children aged 0-48 months diagnosed with AOM in PED during the year 2000 who had a referral letter from a community physician and an AOM diagnosis confirmed by tympanocentesis. AOM antibiotic treatment was considered appropriate when in accord with CDC and local therapeutic guidelines. RESULTS: Referral letter data allowing characterization of AOM by category were available in 471 (79.8%) children, 320 (68%) with simple AOM and 151(32%) with complicated AOM. AOM diagnosis made by the primary care physician was in accord with PED diagnosis in 365/590 (62%) patients. Three hundred and fifty-five (60.2%) patients did not receive antibiotics in the community. Of 365 (62%) children diagnosed with AOM in the community, 235 (64.4%) were treated with antibiotics prior to arrival to PED. Amoxicillin was prescribed to 109 (46.4%), cefuroxime axetil to 48 (20.4%), amoxicillin/clavulanate to 31 (13.2%) and i.m. ceftriaxone to 20 (8.5%) of the patients. Eighty-three (25.9%) patients with simple AOM were treated with antibiotics in the community and only 46 (55.4%) received amoxicillin according to the therapeutic guidelines. Eighty-one (53.6%) patients with complicated AOM were treated with antibiotics in the community and only 41 (50.6%) of them received antibiotics according to AOM therapeutic guidelines. More antibiotics were prescribed in the community to patients with complicated AOM than to patients with simple AOM (81/151, 53.6% versus 83/320, 25.9%, respectively, p < 0.001). Adherence to therapeutic guidelines was similar between the simple and the complicated AOM groups (46/83, 55.4% versus 41/81, 50.6%, respectively, p = 0.5). CONCLUSION: We found partial adherence to AOM therapeutic guidelines among primary care providers in the community in Southern Israel.

Acute Disease↗
PubMed2005

Standardized interpretation of paediatric chest radiographs for the diagnosis of pneumonia in epidemiological studies.

BACKGROUND: Although radiological pneumonia is used as an outcome measure in epidemiological studies, there is considerable variability in the interpretation of chest radiographs. A standardized method for identifying radiological pneumonia would facilitate comparison of the results of vaccine trials and epidemiological studies of pneumonia. METHODS: A WHO working group developed definitions for radiological pneumonia. Inter-observer variability in categorizing a set of 222 chest radiographic images was measured by comparing the readings made by 20 radiologists and clinicians with a reference reading. Intra-observer variability was measured by comparing the initial readings of a randomly chosen subset of 100 radiographs with repeat readings made 8-30 days later. FINDINGS: Of the 222 images, 208 were considered interpretable. The reference reading categorized 43% of these images as showing alveolar consolidation or pleural effusion (primary end-point pneumonia); the proportion thus categorized by each of the 20 readers ranged from 8% to 61%. Using the reference reading as the gold standard, 14 of the 20 readers had sensitivity and specificity of > 0.70 in identifying primary end-point pneumonia; 13 out of 20 readers had a kappa index of > 0.6 compared with the reference reading. For the 92 radiographs deemed to be interpretable among the 100 images used for intra-observer variability, 19 out of 20 readers had a kappa index of > 0.6. CONCLUSION: Using standardized definitions and training, it is possible to achieve agreement in identifying radiological pneumonia, thus facilitating the comparison of results of epidemiological studies that use radiological pneumonia as an outcome.

Child, Preschool↗
PubMed2005

Nasopharyngeal carriage of Streptococcus pneumoniae at the completion of successful antibiotic treatment of acute otitis media predisposes to early clinical recurrence.

OBJECTIVE: We sought to investigate the role of Streptococcus pneumoniae (SP) nasopharyngeal (NP) colonization after successful antibiotic treatment (Rx) of acute otitis media (AOM) in recurrent AOM (RAOM). PATIENTS AND METHODS: NP cultures were obtained from 494 (93%) of 530 patients at the end of antibiotic treatment (EOT). RESULTS: At enrollment, middle ear fluid (MEF) cultures in 418 (79%) of 530 patients were positive for pathogens. At EOT, NP cultures in 208 (42%) of 494 patients were positive for SP. RAOM was found in 130 (26%) of 494 patients: 66 (32%) of 208 with SP-positive NP and 64 of 286 (22%) without SP-positive NP at EOT (P=.026). MEF was positive for SP during RAOM in 34 (61%) of 56 patients with SP-positive NP and 17 (36%) of 47 patients without SP-positive NP at EOT (P=.022). The same serotype was identified in 24 (80%) of 30 SP pairs; complete identity was found between isolates in 22 (96%) of 23 SP pairs. CONCLUSIONS: Early RAOM was more commonly caused by SP if the organism was present in NP at EOT during the initial AOM episode. Most SP-RAOM episodes were caused by SP isolates present in NP at EOT during the previous AOM episode.

Anti-Bacterial Agents↗
PubMed2005

Molecular-size fractionation of pentastarch, radiolabelling with 99mTc, and evaluation of biological behaviour in mice.

BACKGROUND: Pentastarch is used clinically as a plasma volume expander for the management of substantial blood loss. 99mTc labelled pentastarch may be useful as a diagnostic agent in place of 99mTc labelled red blood cells. METHODS: Commercial pentastarch (PS; molecular weight (MW) 240 kDa) was separated according to molecular size by using chromatography, and the fractions were pooled as small (MW 128 kDa), medium (MW 277 kDa) and large (MW 510 kDa) pentastarch. We studied the effect of various physicochemical parameters on the efficiency of radiolabelling with 99mTc and on the stability of the products, and evaluated the biological properties of the 99mTc labelled preparations. RESULTS: We developed an optimised kit formulation containing 3.25 mg pentastarch and 0.13 mg gentisic acid that can be reliably labelled with 99mTc at pH 6.6-8.2 with good stability. In mice, the 99mTc labelled medium pentastarch showed the more favourable blood retention properties (56% of initial blood activity is retained after 3 h) with lower liver levels.

Animals↗