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Biomedical subjects

E A Sanders

Publications and source records attributed to E A Sanders.

At least 19 recordsLinked to original sources

Pneumococcal vaccines for preventing otitis media.

BACKGROUND: Acute otitis media (AOM) is one of the most common diseases in early infancy and childhood. Long term effects of recurrent episodes of otitis media, rapid emergence of drug resistant bacteria associated with AOM worldwide and huge estimated direct and indirect annual costs associated with otitis media have emphasized the need for an effective vaccination program to prevent episodes of AOM. OBJECTIVES: The object of this review was to assess the effect of pneumococcal vaccination in preventing AOM in children up to 12 years of age. SEARCH STRATEGY: We searched the Cochrane Acute Respiratory Infection Group specialised register (last update, 26th April 2001), the Cochrane Library (Issue 4, 2000), MEDLINE (January 1966-August 2000) and reference list of all studies and review articles retrieved. We also contacted two vaccine manufacturers and first or corresponding authors of some included studies. SELECTION CRITERIA: Randomised controlled clinical trials of pneumococcal vaccination with prevention of AOM as outcome in children aged 12 years or younger and a follow-up of at least six months. DATA COLLECTION AND ANALYSIS: Five reviewers independently assessed trial quality and two reviewers extracted data. Two study authors were contacted. MAIN RESULTS: Eight trials on pneumococcal polysaccharide vaccine (PPV) and two trials on pneumococcal conjugate vaccine (PCV) were included. The highest efficacy of PPV was found in children aged 24 months and older: the rate ratio after adjustment for study was 0.833 [95%CI: 0.625-0.970]. The PPV has little effect on the prevention of AOM in children without documented prior episodes of AOM and only a moderate effect in the group of children with documented AOM episodes prior to vaccination. The results of the two PCV trials in healthy infants, which followed children from the age of two months until two years of age, could not be pooled because of lack of data. Both studies showed that the risk of recurrent disease decreased with 9% in the group of children receiving the PCV together with other childhood vaccinations at 2,4,6 and 14 months of age: Study Black et al 2000 : risk ratio=0.91[95%CI:0.86-0.96]; Study Eskola et al 2001: risk ratio=0.90 [95%CI:0.73-1.12]. REVIEWER'S CONCLUSIONS: Based on the currently available results of the effectiveness of pneumococcal vaccination for the prevention of AOM, a large scale use of pneumococcal vaccination for this indication is not recommended. The results of currently ongoing trials could provide more information whether pneumococcal vaccines are effective in specific high-risk (otitis-prone) populations.

Acute Disease↗

Glycine antagonist (GV150526) in acute stroke: a multicentre, double-blind placebo-controlled phase II trial.

GV150526 is a novel glycine antagonist at the NMDA receptor complex. It is a potent neuroprotective agent in animal models of acute stroke including permanent middle cerebral artery occlusion in the rat. GV150526 was very well tolerated in early human studies. The purpose of this randomised, double-blind, multicentre, placebo-controlled trial was to assess the safety and population pharmacokinetics of GV150526 in patients with a clinical diagnosis of acute stroke. Exploratory assessment of efficacy, quality of life and resource utilisation was also undertaken. Upon clinical diagnosis of acute stroke within 12 h of onset of symptoms, patients were treated with a loading dose of 800 mg GV150526 (or placebo), followed by 5 maintenance doses of 400 mg GV150526 (or placebo) given every 12 h over 3 days. Following observation of asymptomatic hyperbilirubinaemia, the maintenance dose was reduced mid-study to 200 mg. CT/MRI scanning was not mandatory prior to treatment. The study treated 128 patients (38 with GV 800 mg/400 mg, 48 with GV 800 mg/200 mg and 42 with placebo). Fewer patients with mild stroke (NIH scores < or =5) were enrolled in the GV150526-treated groups than in the placebo group (placebo 38%, GV 800 mg/400 mg 18%, GV 800 mg/200 mg 15%). There was also an imbalance in the proportion of patients with haemorrhagic strokes (placebo 5%, GV 800 mg/400 mg 3%, GV 800 mg/200 mg 15%). Mortality at 1 month was unbalanced between treatment groups, being 10, 18 and 17% in the placebo, GV 800 mg/400 mg and GV 800 mg/200 mg groups, respectively (no significant difference). Similarly, adverse events, though consistent with an acute stroke population, appeared more often in the GV 800 mg/200 mg group. Functional outcomes at 1 month also showed imbalances, the percentage of patients with a Barthel Index score of > or =95 at 1 month being 52, 39 and 27% in the placebo, GV 800 mg/400 mg and GV 800 mg/200 mg groups, respectively. These results probably reflect a prognostically significant baseline difference between the groups rather than the effect of GV150526. GV150526 was generally well tolerated in patients with a clinical diagnosis of acute stroke and formal efficacy studies were considered justified.

Aged↗

[Vaccination against acute otitis media].

Acute otitis media (AOM) is the most frequent bacterial infection in childhood. Because of the high morbidity, the costs of AOM and growing concern about increasing resistance of pneumococci, the most common bacterial cause of AOM, prevention of AOM is important. Vaccination with the recently developed pneumococcal conjugate vaccines leads to a reduction in the number of AOM cases caused by the serotypes present in the vaccine, but the reduction in overall AOM incidence is below 10%. In particular the children with recurrent episodes of AOM may benefit more from these pneumococcal conjugate vaccines.

Acute Disease↗

[Immunology in medical practice. XVIII [correction of XVII]. Children with recurrent airway problems: asthma is not always the cause.

Three children, two boys aged 16 and 11 years and a girl aged 16 years, with symptoms resembling asthma had been treated for years with inhaled corticosteroids and beta 2-sympathicomimetics without satisfactory results. It was found that the antibody production after vaccination with 23-valent pneumococcal vaccine was impaired. The symptoms diminished during maintenance treatment with antibiotics in two children and with intravenous immunoglobulins in one. In patients with recurrent respiratory problems, but no specific history of asthma, immunological investigation is warranted, especially in patients whose 'asthma' is accompanied by respiratory infections. When treated for their immunodeficiency these patients show remarkable improvement and the need for steroids often disappears.

Adolescent↗

[Invasive infection with Haemophilus influenzae type b in spite of complete vaccination].

Five patients, 4 boys and 1 girl aged 13-41 months, developed invasive Haemophilus influenzae type b (Hib) disease (2 epiglottitis, 3 meningitis) despite full (or at least 3 times) vaccination. At admission as well during convalescence, 3 out of 5 had IgG anti Hib antibody levels < or = 5 U/ml. Serum immunoglobulin levels, including IgG subclasses, as well as complement were normal in all cases. In 2 of the 3, booster vaccinations with Hib conjugate vaccine elicited adequate antibody titres. Since the incorporation of the conjugated Hib polysaccharide tetanus toxoid vaccine (HibTT) in the National Vaccination Programme in the Netherlands, the number of invasive infections caused by Hib has dropped significantly. Causes of Hib conjugate vaccine failures are mostly unknown. In about one-third of the cases serum immunoglobulin levels are deficient, most often IgG2 or IgM. Susceptibility to Hib infection is in part also genetically determined. In the follow-up of Hib vaccine failures, anti Hib antibody titres should be determined. Booster vaccinations may be necessary.

Antibodies, Viral↗

[Immunology in clinical practice. XI. IgG receptors: the role of polymorphism in autoimmune and infectious diseases].

Receptors for the constant part of IgG (Fc gamma R) are implicated in the pathogenesis of a number of diseases. Children from mothers with an Fc gamma RIIIb deficiency may suffer from neonatal neutropenia due to an alloimmune reaction. Interindividual differences (polymorphisms) for a number of Fc gamma R represent risk factors for several infectious and autoimmune diseases. Immunotherapeutic use of several monoclonal antibody subclasses is affected by Fc gamma R polymorphisms. Fc gamma R can be used for cellular entrance by lymphotropic viruses (such as HIV) and appear to be involved in the pathogenesis of fulminant Dengue virus infections.

Animals↗

[Too old for a lumbar hernia operation].

Three patients, one male aged 81 and two females aged 77 and 81, showed a lumbar disc herniation at CT-scan and caudographic examination. Because conservative treatment was unsuccessful and their premorbid health was good, it was decided to perform an operation. All subjects recovered completely, there were no surgical complications. In patients over the age of 70 showing signs and symptoms of nerve root compression one should consider disc herniation. If this is found, surgery is a reliable option despite advanced age. Pre- operative health state is determinative for the decision whether or not to operate on patients of advanced age.

Aged↗

Clinical spectrum of X-linked hyper-IgM syndrome.

We report the clinical and immunologic features and outcome in 56 patients with X-linked hyper-IgM syndrome, a disorder caused by mutations in the CD40 ligand gene. Upper and lower respiratory tract infections (the latter frequently caused by Pneumocystis carinii), chronic diarrhea, and liver involvement (both often associated with Cryptosporidium infection) were common. Many patients had chronic neutropenia associated with oral and rectal ulcers. The marked prevalence of infections caused by intracellular pathogens suggests some degree of impairment of cell-mediated immunity. Although lymphocyte counts and in vitro proliferation to mitogens were normal, a defective in vitro proliferative response to antigens was observed in some patients, and additional defects of cell-mediated immunity may be presumed on the basis of current knowledge of CD40-ligand function. All patients received regular infusions of immunoglobulins. Four patients underwent liver transplantation because of sclerosing cholangitis, which relapsed in there. Three patients underwent bone marrow transplantation. Thirteen patients (23%) died of infection and/or liver disease. X-linked hyper-IgM syndrome, once considered a clinical variant of hypogammaglobulinemia, is a severe immunodeficiency with significant cellular involvement and a high mortality rate.

Bone Marrow Transplantation↗

The risk of brain tumours in hereditary non-polyposis colorectal cancer (HNPCC).

Hereditary non-polyposis colorectal cancer (HNPCC) is known to be associated with several extracolonic cancers, e.g., cancers of the endometrium, stomach, urinary tract, small bowel and ovary. An association between HNPCC and brain tumours has also been reported, although previous risk analysis did not reveal an excess of this type of tumour. To determine whether HNPCC predisposes patients to brain tumours, we used risk analysis to compare families with HNPCC to those in the general population. Of the 1,321 subjects from 50 HNPCC families (with 60,237 person-years of follow-up) in the Dutch HNPCC Registry which satisfy the Amsterdam Criteria, 312 had colorectal cancer. The registry revealed 14 brain tumours in the HNPCC-patients and their first-degree relatives: 5 astrocytomas, 3 oligodendrogliomas, 1 ependymoma and 5 tumours for which a pathological report was not available. The relative risk of brain tumour in patients with HNPCC and their first-degree relatives was 6 times greater than in the general population (95% confidence interval, 3.5 to 10.1). After exclusion of the cases based only on family history, the relative risk was 4.3 (95% confidence interval, 2.3 to 8.0). Although the relative risk of brain tumour was increased, the lifetime risk was low (3.35%). Because it is not certain whether an improvement of the overall prognosis can be achieved by early diagnosis and intervention, and in view of the low lifetime risk, we do not recommend screening for brain tumours in HNPCC families.

Adolescent↗

Surgical repair of traumatically induced collapsing trachea in an ostrich.

A region of tracheal collapse was identified by endoscopy after surgical repair of a traumatic injury to the neck in an ostrich. During periods of excitation, the ostrich would become dyspneic and collapse. A tracheal split-ring prosthesis was placed surgically to support the collapsing trachea. This technique, which is frequently used in dogs, is applicable for use in birds with collapsing trachea.

Animals↗

Simple fed-batch technique for high cell density cultivation of Escherichia coli.

A simple fed-batch process for high cell density cultivation of Escherichia coli TG1 was developed. A pre-determined feeding strategy was chosen to maintain carbon-limited growth using a defined medium. Feeding was carried out to increase the cell mass concentration exponentially in the bioreactor controlling biomass accumulation at growth rates which do not cause the formation of acetic acid (mu < mu crit). Cell concentrations of 128 and 148 g per 1 dry cell weight (g l-1 DCW) were obtained using glucose or glycerol as carbon source, respectively.

Bacteriological Techniques↗

Varicella-zoster virus assembly protein p32/p36 is present in DNA-containing as well as immature capsids.

Varicella-zoster virus (VZV) produces a group of nucleocapsid proteins (the p32/p36 nucleoprotein complex) which are the VZV analogues of the herpes simplex virus type 1 (HSV-1) and cytomegalovirus (CMV) assembly proteins. There are multiple components in the VZV p32/p36 complex, with major proteins of 32 and 36 kDa and minor proteins of 34 and 38 kDa. In HSV-1 the assembly proteins have been shown to be present in immature (B) capsids, but are removed prior to the formation of mature (C) capsids containing the viral DNA genome. Our work has shown that VZV produces capsids corresponding to the B and C forms. However, in contrast to HSV-1, VZV also produces "B/C" capsids that appear to contain both the assembly proteins and the viral DNA genome. Possible mechanisms for this are discussed. In addition, it was shown that VZV capsids appear to lack the 36 and 38 kDa proteins, and based on this observation we suggest that these may represent unprocessed forms of the assembly protein. In both HSV and CMV, a much larger, cross-reactive protein has been identified as the full-length product of the gene coding for the assembly protein. The homologous VZV gene (ORF 33) theoretically has the capacity to produce a 66 kDa protein. However, no such protein is readily apparent in VZV-infected cells. The presence of an immunoreactive 64 kDa protein was demonstrated in purified VZV capsids which may represent the full-length ORF 33 protein.

Antibodies, Monoclonal↗

Effect of growth rate on stability and gene expression of recombinant plasmids during continuous and high cell density cultivation of Escherichia coli TG1.

Continuous and fed-batch cultures of recombinant Escherichia coli TG1 were carried out in order to study plasmid stability and recombinant product formation at different specific growth rates. The aprotinin::beta-galactosidase gene (Ap::lacZ) was placed under the control of two different promoter/repressor systems, the PLac/lacI (pPLac8) and the lambda PL/cIts857 (pPL6) system. The chemically (0.5 mM IPTG) induced gene expression exhibited higher product activity and plasmid stability than the thermally (40 degrees C) induced expression. In fed-batch cultivations with the more stable E. coli TG1(pPLac8) a special feeding strategy allowed bacterial growth with a constant growth rate mu for several hours up to high cell densities. The cloned gene product activity was noticeably effected by the specific growth rate and the cell density at the moment of induction. In particular, the enzyme activities passed a pronounced maximum value in dependence of the set growth rate. The results indicate that fed-batch cultivation strategies are well suited to produce recombinant gene products.

Escherichia coli↗

Production of human parathyroid hormone by recombinant Escherichia coli TG1 on synthetic medium.

Production of human parathyroid hormone (hPTH) by Escherichia coli TG1:I52cIts was studied. The hPTH is expressed as a fusion protein under control of the bacteriophage lambda pR promoter. The organism grows on glucose/mineral salt medium and the expression of the gene product was investigated under variation of temperature and growth rate prior to and after induction. hPTH formation largely depends on cultivation temperature and is optimal for a temperature shift from 30 to 38 degrees C. Product expression is growth coupled and specific hPTH concentration is independent of growth rate. The results are compared with a previous study on E. coli N4830:pEX-PPTH grown on complex media.

Culture Media↗

Deficiency of the beta subunit of the eighth component of complement presenting as arthritis and exanthem.

A 13-year-old boy presented with juvenile chronic arthritis of 6 months' duration. Antinuclear antibodies, anti-double-stranded DNA antibodies, and rheumatoid factor were not detected. Western blotting showed a deficiency of the beta subunit of the eighth component of complement. The same deficiency was present in the patient's sister. C8 beta deficiency is usually detected in individuals who survive meningococcal disease. There was no such history in this family. Juvenile chronic arthritis has not previously been described in patients with C8 beta deficiency.

Adolescent↗

Evaluation of pulse oximetry in horses surgically treated for colic.

All 43 horses anaesthetised for colic surgery were premedicated with xylazine or diazepam. Anaesthesia was induced with guaifenesin and ketamine, horses were placed in dorsal recumbency and anaesthesia was maintained with isoflurane in oxygen and mechanical ventilation. Haemoglobin saturation readings (SpO2) were taken with a pulse oximeter and compared with computed haemoglobin saturation (SaO2) from arterial blood samples. Readings were taken over a range of SaO2 of 78-100%, mean arterial blood pressure ranged from 24 to 108 mmHg and PaO2 ranged from 53 to 490 mmHg. Analysis of 107 readings showed that SpO2 values predicted SaO2 but time, blood pressure and individual horse did not. Correlation coefficients between SpO2 and SaO2 were 0.85 for all values and 0.88 for values at 30 min. Values for bias and precision were calculated for all SpO2 values and for readings separated into 3 saturation groups: normal, low normal, and abnormal. The pulse oximeter tended to underestimate SaO2 at all times, and was less precise as the saturation decreased.

Analysis of Variance↗