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Biomedical subjects

P Ray

Publications and source records attributed to P Ray.

At least 109 records · Page 6Linked to original sources
PubMed1997

Risk of chronic arthropathy among women after rubella vaccination. Vaccine Safety Datalink Team.

CONTEXT: A review by the Institute of Medicine found a possible relationship between rubella vaccination and chronic arthritis among women. OBJECTIVE: To evaluate the risk of persistent joint and neurologic symptoms in rubella seronegative women subsequently vaccinated with RA 27/3 rubella vaccine. DESIGN: Retrospective cohort study based on computerized laboratory data and medical record review. Records were reviewed for symptoms occurring within 2 years before and after the date of serological testing and to identify vaccinees. Possible cases were evaluated by a rheumatologist blinded to serological findings and vaccination status. SETTING: Large health maintenance organization in northern California. PATIENTS: Women aged 15 to 59 years serotested for rubella during 1990 with continuous health plan membership for 2 years before and after the date of their serological test. Seronegative women immunized within 1 year of serotesting (n=971) were defined as exposed. Primary comparison groups included all unvaccinated, seronegative women (n=924) and randomly selected seropositive, unvaccinated women (n=2421) matched to exposed subjects on serological test date and age (+/-3 years). MAIN OUTCOME MEASURES: Prevalence and incidence of chronic joint and neurologic symptoms during 1-year follow-up period stratified by age and serological findings, immunization, and postpartum status. RESULTS: No significantly increased risk was associated with receipt of rubella vaccine for any outcome except for prevalence of carpal tunnel syndrome in vaccinated women at least 30 years old compared with seropositive, unvaccinated women (2.9% vs 1.4%; P=.03). A total of 34 women had onset of conditions within the 1-year follow-up period; 9 of these were in the group of seronegative, immunized women, of whom 6 had onset of symptoms within 6 weeks of vaccination. Among these 6 women, symptoms included transient arthritis or arthralgias (<6 weeks duration) in 4 women, arthralgia of indeterminate chronicity in 1 woman, and carpal tunnel syndrome in 1 woman. Postpartum women across all groups were less likely to be seen for nontraumatic arthropathies than nonpostpartum women (4.5% vs 7.2%, P=.08 in vaccinated women; 4.8% vs 8.1%, P=.09 in seronegative controls; and 4.8% vs 10.0%, P=.01 in seropositive controls). CONCLUSIONS: In this large retrospective cohort analysis there was no evidence of any increased risk of new onset chronic arthropathies or neurologic conditions in women receiving the RA 27/3 rubella vaccine. These data support the continued vaccination of rubella-susceptible women to reduce the risk of congenital rubella syndrome.

Adolescent↗
PubMed1997

Selective up-regulation of cytokine-induced RANTES gene expression in lung epithelial cells by overexpression of IkappaBR.

We previously reported the cloning of a cDNA for IkappaBR (for IkappaB-related) from human lung alveolar epithelial cells. IkappaBR is related to the IkappaB proteins that function as regulators of the NF-kappaB family of transcription factors. Here, we investigated the consequence of IkappaBR overexpression on the expression of NF-kappaB-regulated chemokine genes in lung alveolar epithelial cells. Chemokines play an important role in many inflammatory diseases such as asthma and AIDS. Overexpression of IkappaBR in the lung cells resulted in a rapid 50-100-fold greater production of the RANTES (regulated upon activation, normal T expressed and presumably secreted) protein upon cytokine-induction compared with control cells. IkappaBR overexpression, however, did not enhance interleukin-8 or MIP-1alpha gene expression, despite the fact that the expression of all three chemokine genes are regulated by NF-kappaB. The up-regulation of RANTES gene expression resulting from overexpression of IkappaBR correlated with increased amounts of a unique RANTES-kappaB binding activity and decreased binding of p50 homodimers. Previous studies have shown that p50 homodimers function as repressors of certain kappaB sites. Our studies suggest that IkappaBR can aid activation of select NF-kappaB-regulated genes by sequestering p50 homodimers.

Base Sequence↗
PubMed1997

Acetylcholine exocytosis in PC12 cells deficient in SNAP-25.

Stimulus-induced acetylcholine (ACh) exocytosis from presynaptic nerve terminals involves two important steps: fusion of ACh loaded vesicles at presynaptic release sites, followed by release into the synaptic cleft. We studied the role of the putative vesicle fusion protein SNAP-25 in this process. The nerve growth factor-differentiated PC12 cell line was used as an experimental model. A bee venom tetradecapeptide (INLKALAALAKKIL-NH2) phospholipase A2 (PLA2) activator, mastoparan, was used to induce ACh release. Treatment of PC12 cells with appropriate antisense oligonucleotides blocked SNAP-25 expression, as judged by Western blot protein analysis with a specific monoclonal antibody. Despite apparent elimination of SNAP-25, treatment of differentiated PC12 cells with mastoparan and high (80 mM) K+ induced ACh exocytosis. The results indicate that in PC12 cells, ACh exocytosis due to mastoparan plus K+ can occur in the absence of SNAP-25.

Acetylcholine↗
PubMed1997

Repression of interleukin-6 gene expression by 17 beta-estradiol: inhibition of the DNA-binding activity of the transcription factors NF-IL6 and NF-kappa B by the estrogen receptor.

The cytokine interleukin-6 (IL-6), a key mediator of immune and acute phase responses of the liver, has also been implicated in uterine functions. Estrogens are potent repressors of IL-6 production by uterine stromal cells. In the endometrial adenocarcinoma cell line Ishikawa, phorbol ester-induced activation of the IL-6 promoter was inhibited to basal levels by 17 beta-estradiol (E2) in a wild-type receptor-dependent fashion. Although tamoxifen has been shown to have estrogenic effects on the endometrium, it did not inhibit induction of the IL-6 promoter. We previously showed that inhibition of IL-6 gene expression by E2 does not involve high-affinity binding of the estrogen receptor (ER) to IL-6 DNA. We now report that the ER can directly interact with the transcription factors NF-IL6 and NF-kappa B and can inhibit their ability to bind DNA which might be the molecular basis for repression of IL-6 gene expression by estrogens.

Adenocarcinoma↗
PubMed1997

Fine-needle aspiration biopsy in fungal infections.

To evaluate the role of fine-needle aspiration biopsy (FNAB) in diagnosis of fungal infections, a retrospective analysis of 26 cases of fungal infection is described. The spectrum of various fungi encountered on cytologic microscopy of aspirated material and fungal culture was as follows: Aspergillus sp (16 cases), Cryptococcus neoformans (six cases), Mucorales (one case), Candida sp (one case), Phialophora parasiticus (one case), Sporothrix schenkii and Cladosporium sp (the last two isolated from a single case). In majority (71%) of cases, fungal infection was not clinically suspected but was picked up on cytologic material in all the cases. An accurate diagnosis based on morphology could be made in 21 cases (80%). Predisposing factor was found in three patients, two of them had diabetes mellitus and one was on immunosuppression. HIV serology was negative in seven cases tested. Commonest tissue reaction (75%) was foreign body giant cells with foamy macrophages and variable amount of necrosis. Although FNAB is helpful in the rapid diagnosis of fungal infections, culture is essential for more accurate identification.

Adolescent↗
PubMed1997

Computer-generated recall letters for underimmunized children: how cost-effective?

OBJECTIVE: To evaluate the effectiveness and cost effectiveness of computer-generated recall letters to parents of children overdue for immunizations. METHODS: This randomized controlled trial included children of two facilities in a regional health maintenance organization. Parents of 20-month-olds who had not yet received a measles-mumps-rubella (MMR) immunization were identified via a computerized immunization tracking system. One half were mailed personalized letters that included the recommended immunization schedule and a request to call for an appointment; the other half served as a control group. Receipt of the MMR between 20 and 24 months of age was evaluated with the computerized tracking system. A telephone survey was conducted with parents whose children had not received the MMR by 24 months. Decision analysis was used to project the theoretical outcomes and costs of a recall letter policy for other populations. RESULTS: Among 20-month-old children 10% had not received the MMR; 289 families were included in the analysis. Of families who were mailed letters, 54% (82 of 153) received the MMR by 24 months of age, compared with 35% (47 of 136) of those in the control group (P = 0.001). The telephone survey was completed with 110 parents of children who still did not appear on the health plan computer as having received the MMR by 24 months. Fifteen percent said the child had received an immunization at an outside provider, and of the rest 62% said they had not been aware that an immunization was due. In the cost effectiveness analysis it was projected that recall letters would increase the immunization rate for the regional population of approximately 30000 children from 86% to 90% at a total cost of $5031 annually. The cost per additional child appropriately immunized was $4.04. In sensitivity analyses this cost effectiveness ratio varied depending on the baseline population coverage rate as well as the estimated effectiveness of recall letters. CONCLUSIONS: Computer-generated letters to recall children overdue for immunizations resulted in a higher proportion of children appropriately immunized in this setting. However, the strategy was not as cost-effective as intuition might suggest. Further studies in health maintenance organization (HMO) settings should compare the cost effectiveness of letters with other low cost strategies including automated telephone reminders.

California↗
PubMed1997

Safety and immunogenicity of Chiron/Biocine recombinant acellular pertussis-diphtheria-tetanus vaccine in infants and toddlers.

OBJECTIVE: To evaluate the safety and immunogenicity of the recombinant acellular pertussis-diphtheria-tetanus (aPDT) vaccine (C-aPDT, Chiron/Biocine). STUDY DESIGN: This is a randomized blinded trial evaluating the safety and immunogenicity of the recombinant aPDT vaccine (C-aPDT, Chiron/Biocine) in 2000 infant recipients compared with 498 controls who received whole cell diphtheria-pertussis-tetanus (wDPT; Connaught) vaccine at 2, 4 and 6 months of age. In addition the safety and immunogenicity of the same C-aPDT vaccine were evaluated as a booster dose in a subset of the same population when given at 15 to 18 months of age and compared with licensed Lederle aPDT vaccine. RESULTS: The C-aPDT vaccine was associated with very few local or systemic reactions when compared with wDPT. In toddlers the local and systemic side effects observed were similar after either acellular vaccine. When the immunogenicity of the C-aPDT vaccine was compared with the wDPT (Connaught) in infancy, the vaccines were equivalent for anti-diphtheria response, the wDPT developed higher anti-tetanus response and the C-aPDT vaccine was significantly more immunogenic for all other antigens tested. In toddlers the C-aPDT acellular vaccine exhibited equal or improved immunogenicity for antigens tested as compared with Lederle aPDT except for a higher anti-filamentous hemagglutinin response with the Lederle aPDT vaccine. CONCLUSION: The Chiron/Biocine aPDT vaccine offers an improved safety profile as well as improved immunogenicity when compared with a licensed wDPT product.

Antibodies, Bacterial↗
PubMed1997

Risk of hospitalization because of aseptic meningitis after measles-mumps-rubella vaccination in one- to two-year-old children: an analysis of the Vaccine Safety Datalink (VSD) Project.

OBJECTIVE: To assess the level of increased risk, if any, of hospitalizations for aseptic meningitis after Jeryl-Lynn mumps strain measles-mumps-rubella (MMR) vaccine in the Vaccine Safety Datalink population. STUDY DESIGN: A possible increased risk of aseptic meningitis 8 to 14 days after receipt of MMR was observed in a preliminary screening analysis of automated data from the Vaccine Safety Datalink (VSD) project Year 2 analysis. To further evaluate this association a retrospective 10-year matched case-control study was undertaken in the four health maintenance organizations (HMOs) in the VSD project. Cases ascertained from a broad scan of the automated data were validated against a standard case definition. Two controls matched on age, sex, HMO and HMO membership were assigned per case. RESULTS: The VSD project involves the cooperative collection of automated vaccination and medical outcome data from four large HMOs that currently have 500,000 children younger than 7 years of age under surveillance. Review of automated screening results from the first 2 years of data revealed a possible increased risk of aseptic meningitis 0 to 14 days after MMR with a relative risk of 3.61 (95% confidence interval, 1.0 to 13.1) although the total number of cases was small. Although the automated data had suggested a possible association of aseptic meningitis with MMR containing the Jeryl-Lynn strain of mumps, review of validated hospitalized cases during the observation period did not reveal evidence of an increased risk of aseptic meningitis after MMR containing the Jeryl-Lynn strain of mumps (odds ratio < 1.0 for all analyses). CONCLUSION: Although it is recognized that hospitalized cases represent a minority of the total cases of aseptic meningitis, it is reassuring that in this evaluation no increased risk of aseptic meningitis after MMR vaccine was found.

Case-Control Studies↗
PubMed1997

MMR2 immunization at 4 to 5 years and 10 to 12 years of age: a comparison of adverse clinical events after immunization in the Vaccine Safety Datalink project. The Vaccine Safety Datalink Team.

BACKGROUND: The Advisory Committee on Immunization Practices recommends a second dose of measles, mumps, and rubella vaccine (MMR2) at age 4 to 5 years of age, whereas the American Academy of Pediatrics suggests MMR2 immunization at age 11 to 12 years of age. Because there is little information on whether the rate of adverse reactions to MMR2 immunization varies among these two age groups, we took advantage of differing immunization policies at two large HMOs to compare the frequency of clinical events after, and possibly related to, MMR2 immunization. METHODS: Information was collected on clinical events plausibly associated to MMR immunization (seizures, pyrexia, malaise/fatigue, nervous/musculoskeletal symptoms, rash, edema, induration/ecchymoses, lymphadenopathy, thrombocytopenia, aseptic meningitis, and joint pain) in two cohorts. At three facilities at Northern California Kaiser (Oakland, CA), 8514 children received MMR2 immunization at age 4 to 6 years of age; at Group Health Cooperative (Seattle, WA) 18 036 children received MMR2 immunization at age 10 to 12 years of age. To account for age-related differences in health care use, within each HMO, clinical events in a 30-day period after immunization were compared with a 30-day period before vaccination. RESULTS: Children 10 to 12 years of age were 50% more likely to have a clinical event after MMR2 immunization than in the period before immunization (odds ratio, 1.45; 95% confidence interval: 1.00,2.10). Children 4 to 6 years of age were less likely to have a visit for an event after immunization compared with the period before immunization (odds ratio, 0.64; 95% confidence interval: 0.40,1.01). CONCLUSIONS: These results suggest that the risk for clinical events after MMR2 immunizations is greater in the 10- to 12-year age group.

Adolescent↗
PubMed1997

Iodine nutritional status of the school-age children in South Tripura, North East India.

To evaluate the iodine nutritional status, the thyroids of 3,577 school-age children of both sexes are examined clinically by palpation for goiter prevalence, 345 urine samples are analysed by dry ashing to determine the urinary iodine excretion pattern and 121 edible salt samples collected from house hold are analysed by iodometric titration to monitor the iodinatien achieved through salt from 6 representative areas of South Tripura in goiter endemic North East India. Endemic goiter is found prevalent in all the study areas though its occurrence varies from 13.95% to 30.96%, indicating that clinically mild to severe degree of iodine deficiency prevails in the region. But the pattern of median urinary iodine level of the studied population shows that there is no biochemical iodine deficiency. In 66.94% salt samples had iodine content less than the recommended level of 15 ppm. As per the classification recommended by WHO/UNICEF/ICCIDD, South Tripura falls into goiter endemic by clinical criteria and no endemicity by biochemical criteria. However, iodine deficiency disorders (IDD) continue to be prevalent in the region.

Adolescent↗
PubMed1997

Western blot analysis of serological response in Helicobacter pylori in acid peptic diseases.

A prospective study was undertaken in 70 patients presenting with acid peptic disease with the objective of characterising the serological response to Helicobacter pylori and finding antigens specific for the serodiagnosis of H. pylori infection. H. pylori status was assessed by smear microscopy, rapid urease activity, culture and histopathology of endoscopic gastric antral biopsy specimens. Serological characterisation was carried out by using western blotting of various antigenic components of H. pylori and subsequent enzymatic detection of antibodies against them. Four reactive bands in the molecular weight range of 45-65 kDa were present in all subjects irrespective of H. pylori status. Four to six immunoreactive bands in the molecular weight range of 21-45 kDa were found only in patients with positive H. pylori status and histopathologically proven gastritis. These immunoreactive components may be valuable in specific immunodiagnosis of H. pylori infection.

Adolescent↗
PubMed1996

Targeted expression of IL-11 in the murine airway causes lymphocytic inflammation, bronchial remodeling, and airways obstruction.

Interleukin-11 is a pleotropic cytokine produced by lung stromal cells in response to respiratory viruses, cytokines, and histamine. To further define its potential effector functions, the Clara cell 10-kD protein promoter was used to express IL-11 and the airways of the resulting transgene mice were characterized. In contrast to transgene (-) littermates, the airways of IL-11 transgene (+) animals manifest nodular peribronchiolar mononuclear cell infiltrates and impressive airways remodeling with subepithelial fibrosis. The inflammatory foci contained large numbers of B220(+) and MHC Class II(+) cells and lesser numbers of CD3(+), CD4(+), and CD8(+) cells. The fibrotic response contained increased amounts of types III and I collagen, increased numbers of alpha smooth muscle actin and desmin-containing cells and a spectrum of stromal elements including fibroblasts, myofibroblasts, and smooth muscle cells. Physiologic evaluation also demonstrated that 2-mo-old transgene (+) mice had increased airways resistance and non-specific airways hyperresponsiveness to methacholine when compared with their transgene (-) littermates. These studies demonstrate that the targeted expression of IL-11 in the mouse airway causes a B and T cell-predominant inflammatory response, airway remodeling with increased types III and I collagen, the local accumulation of fibroblasts, myofibroblasts, and myocytes, and obstructive physiologic dysregulation. IL-11 may play an important role in the inflammatory and fibrotic responses in viral and/or nonviral human airway disorders.

Airway Obstruction↗
PubMed1996

FISH detection of chromosome 15 deletions in Prader-Willi and Angelman syndromes.

We have evaluated fluorescence in situ hybridization (FISH) analysis for the clinical laboratory detection of the 15q11-q13 deletion seen in Prader-Willi syndrome (PWS) and Angelman syndrome (AS) using probes for loci D15S11, SNRPN, D15S10, and GABRB3. In a series of 118 samples from patients referred for PWS or AS, 29 had deletions by FISH analysis. These included two brothers with a paternally transmitted deletion detectable with the probe for SNRPN only. G-banding analysis was less sensitive for deletion detection but useful in demonstrating other cytogenetic alterations in four cases. Methylation and CA-repeat analyses of 15q11-q13 were used to validate the FISH results. Clinical findings of patients with deletions were variable, ranging from newborns with hypotonia as the only presenting feature to children who were classically affected. We conclude that FISH analysis is a rapid and reliable method for detection of deletions within 15q11-q13 and whenever a deletion is found, FISH analysis of parental chromosomes should also be considered.

Angelman Syndrome↗
PubMed1996

Clinical experience with preimplantation genetic diagnosis of cystic fibrosis (delta F508).

Preimplantation genetic diagnosis (PGD) was attempted in 12 couples in whom both parents carry the common delta F508 deletion causing cystic fibrosis (CF). In vitro fertilization (IVF) was followed by cleavage stage biopsy on days 2 and 3 and removal of one or two cells for genetic analysis by nested polymerase chain reaction (PCR) and heteroduplex formation. A total of 18 cycles resulted in 137 normally fertilized embryos, of which 115 developed to cleavage stages and 114 were successfully biopsied. Genetic analysis was successful in 83 embryos (73 per cent). With the remaining embryos, either results from two or more cells were discordant or amplification failed. In 15 cycles, one or two either normal or carrier embryos were transferred and five (33 per cent) clinical pregnancies were established. Five singletons have been born and at birth all five babies have been confirmed as homozygous for the normal allele. Our experience demonstrates that IVF and cleavage stage biopsy consistently provides sufficient embryos, diagnosed as unaffected, for transfer in this autosomal recessive disease and that pregnancy rates are comparable to those following IVF.

Adult↗
PubMed1996

A novel 70-kDa Triton X-114-soluble antigen of Plasmodium falciparum that contains interspecies-conserved epitopes.

In order to identify novel conserved integral membrane and other membrane-associated proteins of Plasmodium falciparum, lambda gt11-P. falciparum DNA library phages were immunoscreened with convalescent-phase mouse sera and rabbit antiserum against Triton X-114-soluble proteins of P. falciparum. One recombinant phage clone, L857, reacted with both of the antibody probes. Insert DNA (857 bp long) in L857 was 69% dA+dT rich and hybridized to a fragment of 1800 bp from mung bean nuclease-digested P. falciparum genomic DNA. The cloned parasite DNA did not show notable sequence homology with any known protein gene. The L857-encoded polypeptide, p34 (M(r) 34 kDa) was expressed in bacteria, fused to glutathione S-transferase (GST). The fusion peptide, GST-p34 (M(r) 62 kDa), was recognized by immune serum against Triton X-114-soluble antigens of P. falciparum and was reactive with anti-P. falciparum, anti-Plasmodium yoelii, and anti-GST sera. Rabbit antiserum raised against the fusion peptide recognized a 70-kDa protein from lysates of P. falciparum cells and a putative homologous 100-kDa protein from lysates of P. yoelii. The rabbit serum anti-fusion peptide antibodies bound to acetone-fixed P. falciparum-infected erythrocytes and, in immunofluorescent antibody tests, produced a punctate pattern of fluorescence suggesting that the 70-kDa native protein is associated with an apical organelle of the parasite.

Amino Acid Sequence↗
PubMed1996

Bacteriology of necrotizing infections of soft tissues.

BACKGROUND: Necrotizing infections of soft tissues (NIST) are being attributed to a large variety of organisms, besides the originally described beta-haemolytic Streptococcus. A detailed bacteriological study of these infections was thought worthwhile. METHODS: A prospective study of 55 patients with NIST was carried out. Analysis of surface swabs and debrided tissue for aerobic and anaerobic bacteria and fungal infection was performed. A detailed bacteriological profile was obtained in 50 patients. RESULTS: A total of 257 isolates (167 aerobic, 90 anaerobic) was obtained. One to nine strains of bacteria were isolated from each patient. Aerobic bacteria alone were isolated in 26 patients while the remaining patients grew both aerobic and anaerobic bacteria. Forty-two patients had at least one Gram-positive bacterium while 40 had at least one Gram-negative bacterium. Staphylococcus aureus was the organism isolated most frequently (52%), followed by Bacteroides fragilis (40%) and anaerobic cocci (38%). Group A beta-haemolytic streptococci were isolated in 16%. Blood cultures were positive in only eight patients. Fungal cultures were positive in six patients. Aspergillus fumigatus was the commonest pathogen. CONCLUSIONS: Necrotizing infections of soft tissues are polymicrobial and no single bacterium is associated with a specific clinical entity. Importance should be placed on early recognition and treatment of the disease rather than on isolation of bacteria.

Adolescent↗
PubMed1996

Would better adherence to guidelines improve childhood immunization rates?

OBJECTIVE: To evaluate the contribution of three provider practices to underimmunization of children with financial coverage for vaccines. DESIGN: Retrospective cohort study of children in a large health maintenance organization, based on computerized databases and chart review. SETTING: Large health maintenance organization in northern California. PATIENTS: The population included 24,268 children who had at least one immunization recorded in the health plan tracking system and had continuous health plan membership between 15 and 24 months of age in 1992 through 1993. The study group (N = 4691) were those who had missed one or more of the immunizations due during their second year. RESULTS: Most (57%) of the underimmunized children had made at least one clinic visit between 15 and 24 months of age. Among those underimmunized children who made well care visits, 90% had been partially immunized at the visit but had not been simultaneously given all vaccines for which they were eligible. When a provider did not give all possible vaccines simultaneously, there was a 9% chance that the child would go on to miss the remaining immunization. Simultaneous administration alone would have achieved full second year coverage of 30% of the underimmunized children in this population. Most underimmunized children (53%), including 35% of those children who had not made any well care visits, had made urgent visits between 15 and 24 months of age. Chart review of randomly sampled patients showed no obstacle or contraindication to immunization at 79% of urgent visits and at 71% of well care visits at which vaccines were withheld. A policy to use weekday urgent visits to promote immunization could potentially reach 27% of the underimmunized children. CONCLUSIONS: Provider practices play an important role in underimmunization of children who have insurance coverage for vaccines. Of the three guidelines evaluated, simultaneous administration of all possible vaccines has the greatest potential effectiveness to improve coverage rates in this population. Other guidelines, such as immunizing at urgent visits, are potentially effective but their costs and logistics need further study.

California↗