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Biomedical subjects

P Palmer

Publications and source records attributed to P Palmer.

At least 19 recordsLinked to original sources
PubMed2000

EORTC 10941: A phase II study of liarozole in postmenopausal patients with 'chemotherapy-resistant' or 'potentially hormone sensitive' metastatic breast cancer.

Liarozole is an imidazole compound that inhibits enzymes involved in steroid hormone aromatisation and retinoid metabolism. The IDBBC branch of the EORTC has performed a series of phase II studies of the agent in four groups of postmenopausal women with metastatic breast cancer. This paper reports the results of the first two groups: 'Chemotherapy Resistant' (unrestricted ER status, 1 or 2 prior chemotherapy regimens, 0-2 prior hormonal therapies) and 'Potentially Hormone Sensitive' (ER positive or unknown, 1 or 2 prior hormonal therapies with a substantial disease free interval or progression free survival, and no history of chemotherapy for metastatic disease). Liarozole was administered at 150-300 mg orally bid. The objective response rate was 12% in the 'Chemotherapy Resistant' group (n = 34), and 22% in the 'Potentially Hormone Sensitive' group (n = 37), with median response durations of 9 and 14 months, respectively. Median time to treatment failure was only 2 months in both groups, due largely to the significant percentage (24%) of patients who ceased treatment following excessive mucocutaneous and gastrointestinal toxicity. This adverse event profile will limit its use in breast cancer. Results of the 'ER negative' and 'Tamoxifen Refractory' groups will be reported in a future paper.

Adult↗
PubMed2000

No evidence of measles virus in stapes samples from patients with otosclerosis.

Otosclerosis is a localized bone dystrophy of unknown etiology mainly involving the stapes. The hypothesis of a persistent infection by the measles virus was based on the inconstant detection of the virus by various methods, including reverse transcription-PCR (RT-PCR) of patients' stapes samples. The aim of this work was to investigate the presence of the measles virus in stapedial otosclerosis foci by different sensitive methods. Pathologic stapes samples were obtained from 35 patients suffering from otosclerosis. Measles virus detection was performed by (i) cocultures of Vero cells and primary cell cultures of bone samples (n = 7), (ii) immunofluorescence study of these cocultures (n = 3), and (iii) RT-PCR on RNA directly obtained from fresh frozen samples (n = 28) and on RNA extracted from the primary cell cultures (n = 2). Viral genomic regions coding for N (nucleoprotein) and M (matrix) proteins were separately amplified. PCR sensitivity was optimized on the measles virus Edmonston strain. Glyceraldehyde-3-phosphate dehydrogenase mRNA was used as a marker of total RNA recovery. PCR products were tested by Southern blot hybridization technique to improve sensitivity and specificity. PCRs amplifying the M and the N protein genes were able to detect the control measles virus RNA at titers as low as 0.1 and 0.01 50% tissue culture infective dose, respectively. With these highly sensitive methods, we could not evidence the presence of the measles virus in any of our bone samples or primary bone cell cultures. Our results do not confirm the hypothesis of persistent measles virus infection in otosclerosis.

Adult↗
PubMed1999

An autosomal genomic screen for autism. Collaborative linkage study of autism.

Autism is a severe neurodevelopmental disorder defined by social and communication deficits and ritualistic-repetitive behaviors that are detectable in early childhood. The etiology of idiopathic autism is strongly genetic, and oligogenic transmission is likely. The first stage of a two-stage genomic screen for autism was carried out by the Collaborative Linkage Study of Autism on individuals affected with autism from 75 families ascertained through an affected sib-pair. The strongest multipoint results were for regions on chromosomes 13 and 7. The highest maximum multipoint heterogeneity LOD (MMLS/het) score is 3.0 at D13S800 (approximately 55 cM from the telomere) under the recessive model, with an estimated 35% of families linked to this locus. The next highest peak is an MMLS/het score of 2.3 at 19 cM, between D13S217 and D13S1229. Our third highest MMLS/het score of 2.2 is on chromosome 7 and is consistent with the International Molecular Genetic Study of Autism Consortium report of a possible susceptibility locus somewhere within 7q31-33. These regions and others will be followed up in the second stage of our study by typing additional markers in both the original and a second set of identically ascertained autism families, which are currently being collected. By comparing results across a number of studies, we expect to be able to narrow our search for autism susceptibility genes to a small number of genomic regions. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:609-615, 1999.

Adolescent↗
PubMed1999

Dental implants. 7. Basic restorative techniques.

Some restorative techniques for implant supported restorations will be familiar to dentists used to providing conventional crown and bridgework. The differences and principles involved when using implants are identified.

Dental Abutments↗
PubMed1999

Basic implant surgery.

Implant surgery protocols differ slightly with individual systems. However, basic surgical principles are required to ensure successful osseointegration of the implant in the correct location which allows good aesthetics and loading.

Anesthesia, Dental↗
PubMed1999

[Severe forms of rubella encephalitis: arguments for a better vaccination policy].

BACKGROUND: Two cases of rubella encephalitis in young adults are reported. CASES REPORTS: 2 patients, 19 and 16-year-old, presented with severe encephalitis. One required mechanical ventilation. Neither were vaccinated against rubella. MRI scan of the brain was normal. The diagnosis was confirmed by serology. Good recovery was noted in both patients. DISCUSSION: Both cases of rubella encephalitis occurring in young adults illustrate the severity of this rare disease. As already shown in Finland, improvement with the French vaccination policy should lead to the prevention of rubella encephalitis.

Adolescent↗
PubMed1999

[Coincidental outbreaks of rotavirus and respiratory syncytial virus in Paris: a survey from 1993 to 1998].

PATIENTS AND METHODS: In a pediatric hospital of Paris, from 1993 to 1998, respiratory secretions were positive for respiratory syncytial virus (RSV) in 26.3% of 4,738 children (0-5 years) examined or hospitalized for lower respiratory tract infections. Rotavirus detection was positive in stools of 23.7% of the 8,537 children of the same age with acute diarrhea. RESULTS: The RSV epidemic peak occurred annually in Paris in December and the rotavirus outbreak peaks were observed in December/January. The winter seasonal peaks remained constant for both pathogens and the temporal appearance of these peaks was constant from 1993 to 1998. Fifty to sixty-one percent of rotavirus and 77 to 92% of RSV infections were observed in November, December or January. These simultaneous outbreaks provoked important problems in hospital organization and prevention of nosocomial infections. CONCLUSION: The coincidence of RSV and rotavirus peaks is not found in all countries. The epidemic patterns have to be checked in other parts of France and Europe because this could be important when active immunization programs will be available for these two pathogens.

Child, Preschool↗
PubMed1999

Interferon-alpha in viral and bacterial gastroenteritis: a comparison with C-reactive protein and interleukin-6.

The aim of the study was to identify serum markers able to differentiate bacterial and viral origin in acute diarrhoea. Interferon-alpha (INF-alpha), C-reactive protein (CRP) and interleukin-6 were determined on admission in the sera of 119 children aged between 1 mo and 14 y who were hospitalized for rotavirus (n = 60) or bacterial diarrhoea (Salmonella spp. 39 cases, Shigella spp. 15 cases, Campylobacter jejuni 5 cases). CRP concentration was >10 mg/l in 48.3% of children with viral gastroenteritis and 86.4% of children with bacterial gastroenteritis. IL6 concentration was >100 pg/ml in 11.7% and 26.3% of cases, respectively. INF-alpha was detected in 79.1% of children with rotavirus (sens 79%) and in 3.5% (spec 93%) with bacterial gastroenteritis. However the INF-alpha assay takes 48 h and pathogens are often identified from stools before interferon results are available. We found that serum markers are not discriminating enough to differentiate between viral and bacterial gastroenteritis in emergency cases.

Acute Disease↗
PubMed1999

Comparison of procalcitonin with C-reactive protein, interleukin 6 and interferon-alpha for differentiation of bacterial vs. viral infections.

BACKGROUND: Procalcitonin (PCT) concentration increases in bacterial infections but remains low in viral infections and inflammatory diseases. The change is rapid and the molecule is stable, making it a potentially useful marker for distinguishing between bacterial and viral infections. METHODS: PCT concentration was determined with an immunoluminometric assay on plasma collected at admission in 360 infants and children hospitalized for bacterial or viral infection. It was compared with C-reactive protein (CRP), interleukin 6 and interferon-alpha measured on the same sample. RESULTS: The mean PCT concentration was 46 microg/l (median, 17.8) in 46 children with septicemia or bacterial meningitis. PCT concentration was > 1 microg/l in 44 of 46 in this group and in 59 of 78 children with a localized bacterial infection who had a negative blood culture (sensitivity, 83%). PCT concentration was > 1 microg/l in 16 of 236 children with a viral infection (specificity, 93%). PCT concentration was low in 9 of 10 patients with inflammatory disease and fever. A CRP value > or =20 mg/l was observed in 61 of 236 patients (26%) with viral infection and in 105 of 124 patients (86%) with bacterial infection. IL-6 was > 100 pg/ml in 14% of patients infected with virus and in 53% with bacteria. A secretion of interferon-alpha was found in serum in 77% of viral infected patients and in 8.6% of bacterial infected patients. CONCLUSIONS: In this study a PCT value of 1 microg/l or greater had better specificity, sensitivity and predictive value than CRP, interleukin 6 and interferon-alpha in children for distinguishing between viral and bacterial infections. PCT values are higher in invasive bacterial infections, but the cutoff value of 1 microg/l indicates the severity of the disease in localized bacterial infection and helps to decide antibiotic treatment in emergency room. PCT may be useful in an emergency room for differentiation of bacterial vs. viral infections in children and for making decisions about antibiotic treatments.

Adolescent↗
PubMed1999

Multicenter quality assessment of PCR methods for detection of enteroviruses.

We conducted a multicenter evaluation of commercial and in-house PCR methods for the detection of enteroviruses. Three coded panels of test and control RNA samples, artificial clinical specimens, and representative enterovirus serotypes were used to assess amplification methods, RNA extraction methods, and reactivities with different enterovirus serotypes. Despite several differences between PCR methods, there was good agreement, although some variation in sensitivity was observed. Most PCR methods were able to detect enterovirus RNA derived from 0.01 50% tissue culture infective dose (TCID50) and were able to detect at least 1 TCID50 of enterovirus in cerebrospinal fluid, stool, or throat swab specimens. Most were also able to detect a wide range of enterovirus serotypes, although serotypic identification was not possible. Some laboratories experienced false-positive results due to PCR contamination, which appeared to result mainly from cross-contamination of specimens during RNA extraction. Provided that this problem is overcome, these PCR methods will prove to be a sensitive and rapid alternative to cell culture for the diagnosis of enterovirus infection.

Base Sequence↗
PubMed1999

Psychiatric disorder and the broad autism phenotype: evidence from a family study of multiple-incidence autism families.

OBJECTIVE: Several studies have shown familial aggregation of some axis I psychiatric disorders in families ascertained through a single autistic proband. In this study the authors examined the rate of axis I psychiatric disorders in nonautistic relatives from multiple-incidence autism families and the possible relationship of these disorders to the broad autism phenotype. METHOD: The rates of axis I psychiatric disorders, assessed by using semistructured and family history interviews, were compared in parents, grandparents, and aunts and uncles ascertained through 25 families of multiple-incidence autism probands and 30 families of probands with Down's syndrome. The possible association between selected psychiatric disorders and the broad autism phenotype, assessed directly through semistructured interviews and observational rating measures, was also examined in the two groups of parents. RESULTS: The parents of the autistic probands had significantly higher rates of major depressive disorder and social phobia than the parents of the Down's syndrome probands. The high rate of depression in the parents of the autistic probands was consistent with the high rates of depression and anxiety detected in the grandparents and aunts and uncles in the autism families by family history. There was no evidence of an association, within individuals, between either depression or social phobia and the broad autism phenotype. CONCLUSIONS: Relatives of autistic individuals have high rates of major depression and social phobia that are not associated with the broad autism phenotype and cannot be explained by the increased stress associated with raising an autistic child. Alternative mechanisms and the scientific and clinical implications of these findings are discussed.

Adolescent↗
PubMed1999

FCgammaRII (CD32)-dependent induction of interferon-alpha by serum from patients with lupus erythematosus.

Interferon-alpha (IFN-alpha) is detected in the serum of 70-80% of patients with systemic lupus erythematosus (SLE). Furthermore, soluble factors in SLE serum can induce peripheral blood mononuclear cells (PBMC) to produce IFN-alpha. The purpose of this work was to investigate the mechanism of this IFN-alpha induction. In eleven of fifteen SLE serum samples, an IFN-alpha inducing activity was detected, whereas serum from healthy controls, patients with other autoimmune disease and patients with viral infections were ineffective under the same conditions. After gel filtration of the serum, the inducing activity was found in the same fraction as IgG. The IFN-alpha inducing activity was inhibited by native monoclonal antibodies to the receptors for the Fc portion of IgG: FcgammaRIIA/C and FcgammaRIIB subclasses (CD32) and by their F(ab)'2 fragments. Purified Fc fragments of human IgG were also effective in abolishing the IFN-alpha-inducing activity. Since no anti-CD32 autoantibodies were found in SLE serum, this IFN-alpha-inducing activity may be due to immune complex antibodies. Such results may allow better understand the origin of endogenous IFN-alpha, which has a deleterious effect on the course of this autoimmune disease. The inhibition of this function by the CD32 antibody could lead to new therapeutic approach in SLE.

Antibodies, Monoclonal↗
PubMed1998

[Procalcitonin, C-reactive protein and interleukin 6 in bacterial and viral meningitis in children].

OBJECTIVES: In young children with meningitis, blood or cerebrospinal fluid (CSF) analysis cannot differentiate all cases of viral meningitis (VM) from bacterial meningitis (BM). Empirical antibiotic therapy is often given. As new markers are needed, we compared serum proCalcitonin (PCT) with CSF analysis for C-reactive protein (CRP) and interleukin-6 (IL6). PATIENTS AND METHODS: PCT was measured with a chemoluminescent assay in the sera of 23 children (aged 3 months to 14 years) hospitalized for BM and in 51 patients with VM. RESULTS: Initial CRP (mean 143.3 mg/l, range 28-351 and mean 13.9, range 1-48), CSF proteins (mean 2.2, range 0.4-4.74 and mean 0.57, range 0.12-2.72) and white blood cell count in CSF (range 240-17500 and 20-3200) in BM and VM respectively, were not sufficiently discriminative to distinguish between BM and VM. Twenty-four of the 51 patients with VM were given antibiotics. IL6 values at admission showed an overlap zone (> 100 pg/ml in 7/19 patients with VM and < 100 pg/ml in 1/8 patients with BM. PCT was discriminative in all cases: mean PCT in BM was 61 micrograms/l (range 4.8-335) and 0.33 in VM (range 0-1.7; p < 0.001). No production of PCT was detected in CSF. After antibiotic therapy, PCT decreased and reached undetectable levels after recovery. CONCLUSION: PCT is a sensitive and specific marker for early diagnosis of viral meningitis versus bacterial meningitis in children.

Adolescent↗
PubMed1998

Immunogenicity of pneumococcal vaccine in persons with spinal cord injury.

OBJECTIVE: To determine immunogenicity and optimum timing for administering the 23-valent pneumococcal vaccine after spinal cord injury (SCI). DESIGN: Double-blind, randomized, placebo control study. SETTING: SCI unit in a tertiary care medical center and community. PARTICIPANTS: Eighty-seven persons with recent SCI. INTERVENTION: Participants were randomized to receive either placebo or pneumococcal vaccine at 16 to 18 days versus 4 to 6 months postinjury. MAIN OUTCOME MEASURES: Antibody concentrations were measured prior to intervention and 1, 2, and 12 months afterward to evaluate the immune response to five serotypes of Streptococcus pneumoniae. Effects of demographic and injury-related variables on immune response were also evaluated. RESULTS: Timing of vaccination did not influence mean antibody concentrations for any serotype (p > .05). Ninety-five percent of vaccinated persons had twofold or greater increases in antibody concentration for at least one serotype when measured 1 month after vaccination versus 35% of placebo groups (p < .01). After 12 months, 93% of vaccinated persons in both groups maintained antibody concentrations twofold or greater than baseline values. CONCLUSIONS: Most participants developed an immune response to at least one serotype that was maintained for at least 12 months. Immune response varied according to serotype. Given the favorable immune response and no effect of timing, persons with SCI should receive pneumococcal vaccine during initial hospitalization.

Adolescent↗