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Biomedical subjects

D Webster

Publications and source records attributed to D Webster.

At least 19 recordsLinked to original sources
PubMed2006

Meningococcal meningitis in two patients with primary antibody deficiency treated with replacement intravenous immunoglobulin.

The current treatment of primary antibody deficiency (PAD) is the early recognition of the condition and replacement immunoglobulin combined with prompt treatment of infections and complications. The route of administration (intravenous or subcutaneous), dose and frequency of administration of immunoglobulin still vary between centres and countries. Most infections in patients with PAD are reduced but not entirely prevented by replacement immunoglobulin, with sinopulmonary infections accounting for the bulk of the remainder. Although there have been reports of meningitis in patients with PAD before replacement treatment, we describe the first two cases of bacterial meningitis (group B Neisseria meningitidis) on adequate immunoglobulin replacement and discuss the involvement of potential cofactors.

Adult↗
PubMed2005

Compartmental bone morphometry in the mouse femur: reproducibility and resolution dependence of microtomographic measurements.

Microcomputed tomography (microCT) is widely used for nondestructive bone phenotyping in small animals, especially in the mouse. Here, we investigated the reproducibility and resolution dependence of microCT analysis of microstructural parameters in three different compartments in the mouse femur. Reproducibility was assessed with respect to precision error (PE%CV) and intraclass correlation coefficient (ICC). We examined 14 left femurs isolated postmortem from two strains of mice (seven per group). Measurements and analyses were repeated five times on different days. In a second step, analysis was repeated again five times for a single measurement. Resolution dependence was assessed by high-resolution measurements (10 microm) in one strain and subsequent image degrading. Reproducibility was better in full bone compartment and in cortical bone compartment in the diaphysis (PE%CV = 0.06-2.16%) than in trabecular compartment in the distal metaphysis (PE(%CV) = 0.59-5.24%). Nevertheless, ICC (0.92-1.00) showed a very high reliability of the assessed parameters in all regions, indicating very small variances within repeated measurements compared to the population variances. Morphometric indices computed from lower- and higher-resolution images displayed in general only weak dependence and were highly correlated with each other (R2 = 0.91-0.99). The results show that parameters in the full and cortical compartments were very reproducible, whereas precision in the trabecular compartment was somewhat lower. Nevertheless, all compartmental analysis methods were very robust, as shown by the high ICC values, demonstrating high suitability for application in inbred strains, where highest precision is needed due to small population variances.

Animals↗
PubMed2005

Mycoplasma amphoriforme sp. nov., isolated from a patient with chronic bronchopneumonia.

A mycoplasma was isolated from the sputum of an immunodeficient patient with recurrent bronchitis. The isolate designated strain A39T was very fastidious and atypical for a mycoplasma in its colonial appearance. Classical biochemical tests for mycoplasma speciation could not differentiate the isolate from the pathogens Mycoplasma pneumoniae and Mycoplasma genitalium and serological identification as a recognized Mycoplasma species was lacking. Specific PCR detection for these two species was negative. Subsequently, other strains were isolated from human patients that appeared to be similar to strain A39T in their physiological and genetic characteristics. Analysis of the 16S rRNA gene placed strain A39T and other isolates in the pneumoniae group of mycoplasmas, with the highest sequence similarity to Mycoplasma testudinis (96.8 %), but with only 93.0 % similarity to M. pneumoniae and M. genitalium. Examination of the 16S-23S rRNA internally transcribed spacer sequence, protein electrophoresis profile, genome size and serological reactions indicated that this organism represents a novel species, for which the name Mycoplasma amphoriforme sp. nov. is proposed, with strain A39T (=NCTC 11740T=ATCC BAA-992T) as the type strain.

Bronchopneumonia↗
PubMed2004

Autosomal dominant B-cell immunodeficiency, distal limb anomalies and urogenital malformations (BILU syndrome) - report of a second family.

A family with an unusual combination of B-cell immunodeficiency, distal limb abnormalities, genitourinary malformations, and mild dysmorphic features has recently been described. Here, we report a second family with similar features, which also shows autosomal dominant inheritance. In affected individuals from both families, sequence analysis of candidate gene HOXA13 did not identify a mutation, and there was no evidence of a microdeletion involving either HOXA13 or the HOXA cluster as a whole. We further delineate the phenotype of this condition in females and add weight to the observation that this is a true syndromic association.

Adult↗
PubMed2003

Chronic bronchitis in immunocompromised patients: association with a novel Mycoplasma species.

Patients with primary antibody deficiency are prone to recurrent bronchitis, often caused by nonencapsulated Haemophilus influenzae and streptococcal infection. Productive cough often persists even after elimination of these organisms with antibiotics. During an investigation into the cause of unexplained chronic bronchitis in these patients, a novel Mycoplasma species (designated A39) was first isolated from the sputum of a man with X-linked agammaglobulinaemia. Screening of sputa from a further 45 patients with primary antibody deficiency showed that 10 were positive for a similar organism using culture and/or a polymerase chain reaction based on sequences within the 16S ribosomal RNA gene. A comparison of the sequence data showed that the organism was distinct from but similar to Mycoplasma pneumoniae and other closely related mycoplasmas found in humans and animals. Electron microscopy showed some unique morphological characteristics. Although respiratory symptoms improved after elimination of A39 from the sputum of the patient with X-linked agammaglobulinaemia, further work is needed to establish the organism as a pathogen.

Adult↗
PubMed2001

Plant-derived measles virus hemagglutinin protein induces neutralizing antibodies in mice.

Measles remains a significant problem in both the developed and developing world, and new measles vaccination strategies need to be developed. This paper examines the strategy of utilizing transgenic plants expressing a measles antigen for the development of an oral sub-unit measles vaccine. A 1.8 kb fragment encompassing the coding region of the measles virus hemagglutinin (H) protein was cloned into a plant expression cassette. Three different expression constructs were tested: pBinH (H gene alone), pBinH/KDEL (addition of a C-terminal endoplasmic reticulum-retention sequence SEKDEL) and pBinSP/H/KDEL (further addition of an authentic N-terminal plant signal peptide). The highest levels of recombinant H protein production were observed in plants transformed with pBinH/KDEL. Mice inoculated intraperitoneally with transgenic plant derived recombinant H protein produced serum anti-H protein antibodies that neutralized the measles virus (MV) in vitro. Mice gavaged with transgenic tobacco leaf extracts also developed serum H protein-specific antibodies with neutralizing activity against MV in vitro. These results indicate that the plant-derived measles H protein is immunogenic when administered orally and that, with further development, oral vaccination utilizing transgenic plants may become a viable approach to measles vaccine development.

Administration, Oral↗
PubMed2001

Does 77C-->G in PTPRC modify autoimmune disorders linked to the major histocompatibility locus?

A 77G allele of the gene encoding CD45, also known as the protein tyrosine phosphatase receptor-type C gene (PTPRC), has been associated with multiple sclerosis (MS). Here we determine allele frequencies in large numbers of MS patients, primary immunodeficiencies linked to major histocompatibility complex (MHC) locus and over 1,000 controls to assess whether aberrant splicing of PTPRC caused by the 77C-->G polymorphism results in increased susceptibility to these diseases. Our results show no difference in the frequency of the 77G allele in patients and controls and thus do not support a causative role for the polymorphism in the development of disorders with a strong autoimmune component in etiology.

Animals↗
PubMed2001

Treatment of resistant mycoplasma infection in immunocompromised patients with a new pleuromutilin antibiotic.

Patients with primary antibody deficiency (PAD) are prone to mycoplasma infection with unusual strains which may be resistant to conventional antibiotics. Mycoplasmas were isolated from the joint fluid (Ureaplasma urealyticum) of two PAD patients with arthritis and from the cerebral spinal fluid (Mycoplasma maculosum) in one with meningitis, the latter probably originating from the patient's dog. Combinations of doxycycline and quinolones or macrolides failed to clear the infections, but after demonstrating in-vitro sensitivity to the pleuromutilin, Econor, for two of the isolates, all three patients responded to oral treatment with Econor. The infection was completely eradicated in two patients, with the emergence of a resistant strain in the third. Mycoplasma infection should be considered in PAD patients with unexplained sepsis. Pleuromutilins such as Econor are powerful new anti-mycoplasmal agents which provide an additional therapeutic option when patients fail to respond to conventional antibiotics.

Adolescent↗
PubMed2001

The role of alcohol use in intimate partner femicide.

The purpose of this study was to examine alcohol use by victims and perpetrators as a risk factor for intimate partner violence and femicide. A case control design was used to describe alcohol use among Femicide/Attempted Femicide victims (n = 380), Abused Controls (n = 384) and Non-Abused Controls (n = 376), and their intimate partners. Telephone interviews of proxies (family members or friends) of femicide victims and actual survivors of attempted femicide were conducted in 10 cities. The purpose of the interviews was to gather information about relationship violence and alcohol use by femicide victims, attempted femicide survivors, and their perpetrators. Telephone interviews of controls, recruited from the same cities by random digit dialing, were also conducted. Perpetrator problem drinking was associated with an eight fold increase in partner abuse (e beta = 8.24, p < .0001) and a two fold increased risk of femicide/attempted femicide (e beta = 2.39, p = .001), controlling for demographic differences.

Adolescent↗
PubMed2001

Long term recovery of IgG and IgM production during HIV infection in a patient with common variable immunodeficiency (CVID).

AIMS: Common variable immunodeficiency (CVID) is the most common serious primary immunodeficiency. This paper describes the immunological consequences of human immunodeficiency virus (HIV) infection in a patient with familial CVID subsequently treated with highly active antiretroviral therapy (HAART). METHODS: Serial measurements over 11 years of serum immunoglobulins, specific antibodies to tetanus toxoid and pneumococcal polysaccharides, lymphocyte phenotypes, and HIV viral load were made. RESULTS: The patient recovered total serum IgG and IgM, but not IgA production, with adequate concentrations of specific antibodies, allowing withdrawal of intravenous immunoglobulin without an increase in infections. T cell numbers gradually declined and the patient developed a high grade B cell lymphoma. After successful chemotherapy, HAART was commenced, viral load fell from 472 000 to < 50 copies/ml, and CD4+ T cell numbers increased from 13 to 661 x 10(6)/litre. Antibody production was maintained after suppression of viral load. CONCLUSIONS: This is the first definitive report of reversal of IgG and IgM deficiency in familial CVID after HIV infection. Failure to normalise IgA supports the concept of separate predisposing genetic factors for selective IgA deficiency, which when combined with others lead to CVID. Furthermore, a persistently high viraemia is not required to maintain the recovery of immunoglobulin values, suggesting this depends either on a transitory effect of a high viral load, or a persistence of low amounts of virus.

Adult↗
PubMed2001

Cochlear implantation of a patient with a previously undescribed mitochondrial DNA defect.

Mitochondrial DNA (mtDNA) defects are responsible for symptom complexes that are characteristically heterogeneous but are typically represented by muscle weakness and neurological deficits. One common feature of mitochondrial disease is deafness. This report details the assessment and outcome of a patient with a previously undescribed mtDNA rearrangement who underwent cochlear implantation. The patient shows a marked improvement in sentence recognition tests and recognition of environmental sounds. Patients with profound sensorineural hearing loss due to mtDNA defects should be considered as candidates for cochlear implantation when they no longer benefit from conventional hearing aids.

Adult↗
PubMed2001

Using wound fluid analyses to identify trace element requirements for efficient healing.

A series of wound fluid and blood plasma samples from 20 patients with breast cancer were analysed by Potentiometric Stripping Analysis and computer-aided chemical speciation to quantify the concentrations of the trace elements of copper and zinc in the samples and to investigate the individual species of copper and zinc present. Comparisons were made between total concentrations of copper and zinc in wound fluid, pre-operative blood plasma levels and reference values. A wound fluid model constructed using JESS identified the main copper and zinc species present. It was also used to investigate the effects of a change in pH and changes in the total concentrations of certain components on their predominance. The clinical significance of the research is discussed, together with suggestions for a continuation in the research.

Breast Neoplasms↗
PubMed2000

Impaired antibody affinity maturation process characterizes a subset of patients with common variable immunodeficiency.

Common variable immunodeficiency (CVID) is an heterogeneous syndrome characterized by decreased levels of serum Ig and recurrent bacterial infection. Here, we were interested to study whether a qualitative defect of the affinity Ab maturation process could be combined to the low level of serum Ig in a cohort of 38 CVID patients. For this, we designed a novel and rapid screening test for the detection of hypomutated V gene expressed by memory B cells. This test delineated a subset of 9/38 (23%) CVID patients with an abnormal pattern of Ig V gene mutation. The mean frequency of V gene mutation of this subset was significantly lower (1.74%) compared with other CVID patients (5.46%) and normal donors (6.5%) (p<0.0001). The mean age of this subgroup was significantly higher than other hypogammaglobulinemic patients with normal levels of V gene mutation (p<0.02), whereas no difference in the duration of symptoms was noted between the two groups. This suggests that hypomutation characterizes patients who began CVID late in life. Recently, it was shown that non-Ig sequences, such as the intronic BCL-6 gene, could be the target of the somatic hypermutation process in normal memory B cells. Our finding of a normal mutation frequency of the BCL-6 gene in two hypomutated CVID point to a defect of the Ig targeting of hypermutation machinery in these cases.

Adult↗
PubMed2000

Randomized trial of a specialist genetic assessment service for familial breast cancer.

BACKGROUND: Because of the growing demand for genetic assessment, there is an urgent need for information about what services are appropriate for women with a family history of breast cancer. Our purpose was to compare the psychologic impact and costs of a multidisciplinary genetic and surgical assessment service with those of current service provisions. METHODS: We carried out a prospective randomized trial of surgical consultation with (the trial group) and without (the control group) genetic assessment in 1000 women with a family history of breast cancer. All P: values are from two-sided tests. RESULTS: Although statistically significantly greater improvement in knowledge about breast cancer was found in the trial group (P: =.05), differences between groups in other psychologic outcomes were not statistically significant. Women in both groups experienced statistically significant reductions in anxiety and found attending the clinics to be highly satisfying. An initial specialist genetic assessment cost pound 14.27 (U.S. $22.55) more than a consultation with a breast surgeon. Counseling and genetic testing of affected relatives, plus subsequent testing of family members of affected relatives identified as mutation carriers, raised the total extra direct and indirect costs per woman in the trial group to pound 60.98 (U.S. $96.35) over costs for the control subjects. CONCLUSIONS: There may be little benefit in providing specialist genetics services to all women with a family history of breast cancer. Further investigation of factors that may mediate the impact of genetic assessment is in progress and may reveal subgroups of women who would benefit from specialist genetics services.

Adult↗
PubMed2000

Morphological and biochemical evaluation of RAW 264.7 cells exposed to polychlorinated biphenyl.

The effects of PCBs exposure, at low doses ranging between 10-100 mg PCB (Arclor-1254), on the viability of RAW 264.7 macrophage cells after 24, 48, and 72 hours of incubation was investigated. Furthermore, this study was designed to determine the interrelationship between PCBs and estrogen (E, 10 mg) and its role in the viability of RAW cells. Macrophages were cultured and plated in 24 well-plates according to standard protocols. The wells were divided into eight groups (n = 4 wells/group, 1 x 10(4) cells/well). The cells in groups 1-3 were treated with vehicle (serum-control for estrogen, DMSO-control for PCB, and media alone, respectively). Cells in groups 4 and 5 were treated with low (10 mg) and high (100 mg) doses of PCB. Cells in group 6 were treated with E, and cells in groups 7 and 8 were treated with low dose PCB + E and high dose PCB + E, respectively. Cell viability and damage (Malianodialdehyde, MDA level) were determined after 24, 48, and 72 hours, as well as, cell morphology. The results of this study showed that low and high doses of PCB depressed cell number by 52%. Estrogen treatment caused no effect on cell number in comparison to cells treated with serum alone. Cell number in response to E and low and high doses of PCB decreased cell number by 50%. Similar results were also observed at 48 hour time phase. In contrast, at the 72 hour phase, no significant changes were observed for cell count. Morphological evaluation of the cells revealed healthy spindle shaped multinucleated cells in the control group but, groups exposed to PCB induced morphological changes that included: cells became small, round, and increased evidence of cellular injury and debris. Estrogen treatment did not show changes from the control group. However E and PCB treatments caused the cells to become round, tightly compact nuclei with evidence of cell fragmentation. The results of this investigation showed that exposure to either 10 or 100 mg of PCB had detrimental effects on the RAW 264.7 macrophage cells as early as 24 hours. Combination treatment with E didn't provide any protective measures to the viability of RAW cells exposed to PCBs.

Animals↗