Pertussis in Massachusetts, 1981-1991: incidence, serologic diagnosis, and vaccine effectiveness

Massachusetts provides diphtheria-tetanus toxoid-pertussis (DTP) vaccine, and since 1980 has monitored pertussis with a statewide diagnostic service. The incidence of bacteriologically confirmed pertussis was 104.5 per 100,000 person-years in 1-month-old infants and declined progressively thereafter. Infants < 6 months old experienced disproportionate morbidity: 44% of bacteriologically confirmed pertussis, 64% of hospitalizations, and 71% of hospital days. Most children with pertussis had received < 3 DTP doses during childhood, whereas 87% of adolescents with pertussis had received > or = 4 doses. Serodiagnosis by single serum anti-pertussis toxin antibody ELISA increased the incidence of confirmed pertussis in persons 11-19 years old from 3.0 to 12.9 per 100,000 and in persons > or = 20 years old from 0.16 to 0.56 per 100,000. Bacteriologic methods underestimate pertussis incidence, but a single serum anti-pertussis toxin antibody ELISA is a practical method for population-based diagnosis in adolescents and adults.     

Alternative splicing in fibroblast growth factor receptor 2 is associated with induced epithelial-mesenchymal transition in rat bladder carcinoma cells

We described previously that acidic fibroblast growth factor (aFGF), but not basic fibroblast growth factor (bFGF), can induce the rat carcinoma cell line NBT-II to undergo a rapid and reversible transition from epithelial to mesenchymal phenotype (EMT). We now find that NBT-II EMT is stimulated by keratinocyte growth factor (KGF) in cells grown at low density. Accordingly, a high-affinity receptor showing 98% homology to mouse FGF receptor 2b/KGF receptor was cloned and sequenced from NBT-II cells. Northern analysis indicated that mRNA for FGF receptor 2b/KGF receptor was drastically down-regulated within 1 wk in aFGF-induced mesenchymal NBT-II cells. This decrease coincided with an up-regulation of FGF receptor 2c/Bek, a KGF-insensitive, alternatively spliced form of FGF receptor 2b/KGF receptor. Functional studies confirmed that KGF could not maintain EMT induction on mesenchymal NBT-II cells. FGF receptor 1 and FGF receptor 2c/Bek could also support EMT induction when transfected into NBT-II cells in response to aFGF or bFGF. Such transfected cells could bind bFGF as well as aFGF. Therefore, EMT can be induced through different FGF receptors, but EMT may also regulate FGF receptor expression itself.     

Effect of vitamin A supplementation on diarrhoea and acute lower-respiratory-tract infections in young children in Brazil

A beneficial effect of periodic vitamin A supplementation on childhood mortality has been demonstrated, but the effect on morbidity is less clear. We investigated the effect of vitamin A supplementation on diarrhoea and acute lower-respiratory-tract infections (ALRI) in children from northeastern Brazil in a randomised, double-blind, placebo-controlled community trial. 1240 children aged 6-48 months were assigned vitamin A or placebo every 4 months for 1 year. They were followed up at home three times a week, and data about the occurrence and severity of diarrhoea and ALRI were collected. Any child with cough and respiratory rate above 40 breaths per min was visited by a paediatrician. The overall incidence of diarrhoea episodes was significantly lower in the vitamin-A-supplemented group than in the placebo group (18.42 vs 19.58 x 10(-3) child-days; rate ratio 0.94 [95% Cl 0.90-0.98]). The benefit of supplementation was greater as regards severe episodes of diarrhoea; the incidence was 20% lower in the vitamin A group than in the placebo group (rate ratio 0.80 [0.65-0.98]). With the standard definition of diarrhoea (> or = 3 liquid or semi-liquid stools in 24 h) the effect of vitamin A on mean daily prevalence did not reach significance, but as the definition of diarrhoea was made more stringent (increasing number of stools per day), a significant benefit became apparent, reaching for diarrhoea with 6 or more liquid or semi-liquid stools in 24 h a 23% lower prevalence. We found no effect of vitamin A supplementation on the incidence of ALRI. The reduction in severity of diarrhoea may be the most important factor in the lowering of mortality by vitamin A supplementation.     

Intracellular location of inapparently infecting Chlamydia in synovial tissue from patients with Reiter's syndrome

Culture of Chlamydia trachomatis from synovial tissues/fluids from Reiter's syndrome (RS) patients frequently yields negative results. However, we have identified chlamydial RNA at that site in such patients, suggesting that viable organisms may be present. Here we define the cellular location of chlamydia within the synovium via in situ hybridization. Using a chlamydial ribosomal RNA-directed probe, we show that synovial tissue from culture-negative RS patients gives strong hybridization which is often localized to a subsynovial cell layer, rather than to the synovial lining; in some cases, hybridizing cells are dispersed through the synovium. All hybridization signal is located within host cells, indicating that infectious extracellular elementary bodies are rare or absent. These data confirm the extensive intracellular presence of inapparent chlamydia in the synovia of RS patients and provide some insight into the usual culture negativity of synovial tissues for the organism.     

Distal 6p deletion syndrome: a report of a case with anterior chamber eye anomaly and review of published reports

We describe a 32 year old male with a distal 6p24.3-->pter deletion. He has specific developmental anomalies of the anterior chamber of the eye and a cleft uvula which is consistent with the recent localisation of genes for iris development and orofacial clefting to distal 6p. In addition he has progressive sensorineural deafness and this may localise a gene for deafness to this region. We conclude that a refined distal 6p deletion syndrome exists and includes a characteristic facial appearance with hypertelorism, downward slanting palpebral fissures, tented mouth, smooth philtrum, palatal malformation, ear anomalies, anterior chamber eye defects, progressive sensorineural deafness, cardiac defects, abdominal herniae, small external genitalia, and motor and speech delay.     

Microbiological examinations and in-vitro testing of different antibiotics in therapeutic endoscopy of the biliary system

BACKGROUND AND STUDY AIMS: Prior to endoscopic therapeutic procedures, no antibiotic prophylaxis is administered routinely. Because of the reported incidence of infectious complications, which may reach up to 10%, a prospective study was undertaken to investigate the effects of a prophylactic dose of cefuroxime on the incidence of bacteremia and clinical signs of infection, but no significant effects could be demonstrated. In addition to this published work, blood and bile cultures obtained in this trial were also investigated, and the in-vitro susceptibility to several antibiotics was tested in order to recommend the appropriate substances. PATIENTS AND METHODS: Ninety-nine consecutive patients (51 men, 48 women; mean age 61.4 +/- 17 years) with biliary obstruction who underwent an endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography with drainage (PTCD) were included. Sequential blood cultures were taken before and up to 60 minutes after the endoscopic intervention. Bile cultures were obtained in 56 patients with biliary drainage. Aerobic and anaerobic cultures were prepared from all obtained specimens and the isolated organisms were identified. In the case of positive cultures, an in-vitro resistance test for 15 different antibiotics was performed. RESULTS: The incidence of bacteremia was 11.1% (n = 11), and 16 bacteria were isolated. Twelve different microorganisms were detected, with Escherichia coli found in four cases. From 41 positive out of 56 prepared bile cultures (73.2%), 91 isolates were found with 25 different species. A single agent was detected in eight cases (19.5%), while a mixed growth, with pathogens ranging from two to six species, was found in 33 cases (80.5%). The seven most frequently isolated germs were E. coli and Enterococcus (each n = 19), Klebsiella (n = 10), Streptococcus viridans (n = 9), Staphylococcus epidermidis (n = 5), Morganella morganii (n = 4), and Bacteroides fragilis (n = 3), representing 76% of all agents. Examination for fungal infection revealed positive cultures of Candida albicans in 16.1% of bile cultures (nine of 56). Interestingly, the use of proton-pump inhibitors (PPIs), with a consequent rise in the gastric pH value, led to an increase in the rate of bacteremia to 26.2% (five of 19) compared to the other patients not on PPIs (n = 80), who developed bacteremia in only six cases (7.5%; p = 0.02). In-vitro testing of different antibiotics was carried out in 73 isolates. Imipenem showed the best antimicrobial activity (98.4%), followed by trimethoprim and sulfamethoxazole (90%), amoxicillin plus clavulanic acid (87.3%), vancomycin (82.4%), and ofloxacin (76.9%). CONCLUSIONS: Escherichia coli was found to be the pathogen most frequently detected in blood and bile following endoscopic interventions in the biliary tract. Enterococci, Klebsiella and Streptococcus viridans were found in bile cultures with an incidence exceeding 10%. In view of the in-vitro test results, possible side effects, and contraindications, amoxicillin plus beta-lactamase inhibitors or quinolones are considered to be suitable antibiotics for the prophylaxis of biliary infections.     

Interleukin (IL)-10, IL-12, and interferon-gamma production in primary and memory immune responses to varicella-zoster virus

Varicella immunization provided the opportunity to examine the kinetics of interleukin (IL)-10, IL-12 and interferon (IFN)-gamma production elicited during primary in vivo sensitization with proteins of varicella-zoster virus (VZV), a common human herpesvirus. VZV-specific IFN-gamma release and T cell proliferation were elicited by immunization and persisted through 15 months of follow-up. The induction of VZV-specific T cells and IgG antibodies was accompanied by transient increases in IL-10 and IL-12 production. T cell proliferation to VZV was significantly lower in adults at 15 months than in vaccinated children or naturally immune subjects and correlated with lower IFN-gamma responses in individual vaccinees. After primary immunity was induced, continued IL-12 production was not necessary to maintain the predominant Th1-type response elicited by VZV. Cytokine profiles observed during primary in vivo sensitization to VZV suggest that parallel increases in IFN-gamma and IL-10 may be important in the induction of immunity to some viral pathogens.     

Repressor titration: a novel system for selection and stable maintenance of recombinant plasmids

The propagation of recombinant plasmids in bacterial hosts, particularly in Escherichia coli, is essential for the amplification and manipulation of cloned DNA and the production of recombinant proteins. The isolation of bacterial transformants and subsequent stable plasmid maintenance have traditionally been accomplished using plasmid-borne selectable marker genes. Here we describe a novel system that employs plasmid-mediated repressor titration to activate a chromosomal selectable marker, removing the requirement for a plasmid-borne marker gene. A modified E.coli host strain containing a conditionally essential chromosomal gene (kan) under the control of the lac operator/promoter, lac O/P, has been constructed. In the absence of an inducer (allolactose or IPTG) this strain, DH1 lackan , cannot grow on kanamycin-containing media due to the repression of kan expression by LacI protein binding to lac O/P. Transformation with a high copy-number plasmid containing the lac operator, lac O, effectively induces kan expression by titrating LacI from the operator. This strain thus allows the selection of plasmids without antibiotic resistance genes (they need only contain lac O and an origin of replication) which have clear advantages for use as gene therapy vectors. Regulation in the same way of an essential, endogenous bacterial gene will allow the production of recombinant therapeutics devoid of residual antibiotic contamination.     

Experience in the study of the effects of lead on the health status of children in Belovo]

Lead releases in Belovo town containing metallurgy enterprise had reached 120 tons/year earlier, but in recent years have decreased to 9 tons/year. Reduction of the production induced decrease of lead levels in the ambient air from 0.7-2.3 mg/m3 in 1994 to 0.001-0.24 mg/m3. Lead concentration in the soil ranges from 30 to 3000 mg/kg. Lead levels were measured in serum of 91 children, in hair of 67 ones and in teeth of 15 children. Serum lead levels in children aged 7-8 years varied from 0.5 to 39 mg/dl, with an average of 9.9 mg/dl (SD is 5.2 mg/dl), geometric mean is 8.5 mg/dl and error of geometric mean is 3.3. 46% of the children had serum lead levels exceeding the normal one (10 mg/dl). Average lead level in the hair equaled 4.5 mg/g (SD is 4.9 mg/g). The children living in towns with higher environmental lead levels demonstrated more frequent anxiety and changes in higher psychic functions. The major points influencing the serum lead level are proximity to highway, dietary load of goods grown near the residence, mother's smoking. Biokinetic model describing lead transfer into the blood helped to evaluate various modes of the enterprise functioning and efficiency of some environmental protection measures. The most efficient are measures aimed to lower dietary intake of lead, less efficiency is associated with measures reducing lead levels in air, dust and soil.