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Biomedical subjects

R Edelman

Publications and source records attributed to R Edelman.

At least 55 records · Page 3Linked to original sources

Primary radiotherapy of T1 and T2 glottic carcinoma--analysis of treatment results and prognostic factors in 223 patients.

Treatment results in 223 patients with T1 and T2 glottic carcinoma were analysed. A multivariate analysis was performed to evaluate the prognostic significance of factors related to tumour, patient and treatment. Locoregional control after radiotherapy was 90% for 129 patients with T1 tumours and 73% for 94 with T2 tumours. Disease-specific survival was 96% and 81% for patients with T1 and T2 tumours, respectively. In the multivariate analysis of locoregional control, subglottic extension contributed prognostic information to T-stage. In the univariate analysis, number of involved tumour sites, cord mobility and treatment interruption had a significant influence, which was lost in the multivariate analysis. Age gave additional prognostic information in the multivariate analysis of disease-specific survival. Significant adverse effects of radiotherapy were found in 9 patients (4%). Forty-nine patients (22%) had a second malignancy, 11 (5%) diagnosed before the glottic carcinoma.

Adult↗

High seroprevalence of hepatitis A, B, C, and E viruses in residents in an Egyptian village in The Nile Delta: a pilot study.

Hepatitis C virus (HCV) infection is hyperendemic in Egypt, with seroprevalence rates of 10-20% among volunteer blood donors, and even higher rates reported among segments of the general population. We attempted to confirm the high seroprevalence of HCV and to compare it with the age-specific seroprevalence rates for hepatitis A, hepatitis B, and hepatitis E among 155 nonrandomly selected residents of a semiurban village in the Nile River delta. Of the two orally transmitted viruses (HAV and HEV), all 1-3-year-old children had been infected by HAV and the seroprevalence rate of 100% persisted until age 67. In contrast, HEV infections were not detected until children were 4-9-years old, and the 57% seroprevalence rate in this age group did not increase appreciably in older age groups. Of the two parenterally transmitted viruses, HBV was first detected in 1-3-year-olds, whereas HCV was first detected later, in 10-19-year-olds. The seroprevalence rates of both viruses increased progressively with age, peaking in the 40-67-year-old group at 66% for HBV and at 51% for HCV. The number of persons who had only one infection, or no infection at all, was too small to allow meaningful statistical analysis of serologically pure groups infected only by HBV, HCV, or HEV. The results of this pilot study revealed extraordinarily high seroprevalence rates of HBV, HCV, and HEV in this village, and distinctive age-specific seroprevalence rates suggesting different patterns of transmission.

Adolescent↗

Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant. The Vaginal Infections and Prematurity Study Group.

BACKGROUND: Bacterial vaginosis is believed to be a risk factor for preterm delivery. We undertook a study of the association between bacterial vaginosis and the preterm delivery of infants with low birth weight after accounting for other known risk factors. METHODS: In this cohort study, we enrolled 10,397 pregnant women from seven medical centers who had no known medical risk factors for preterm delivery. At 23 to 26 weeks' gestation, bacterial vaginosis was determined to be present or absent on the basis of the vaginal pH and the results of Gram's staining. The principal outcome variable was the delivery at less than 37 weeks' gestation of an infant with a birth weight below 2500 g. RESULTS: Bacterial vaginosis was detected in 16 percent of the 10,397 women. The women with bacterial vaginosis were more likely to be unmarried, to be black, to have low incomes, and to have previously delivered low-birth-weight infants. In a multivariate analysis, the presence of bacterial vaginosis was related to preterm delivery of a low-birth-weight infant (odds ratio, 1.4; 95 percent confidence interval, 1.1 to 1.8). Other risk factors that were significantly associated with such a delivery in this population were the previous delivery of a low-birth-weight infant (odds ratio, 6.2; 95 percent confidence interval, 4.6 to 8.4), the loss of an earlier pregnancy (odds ratio, 1.7; 1.3 to 2.2), primigravidity (odds ratio, 1.6; 1.1 to 1.9), smoking (odds ratio, 1.4; 1.1 to 1.7); and black race (odds ratio, 1.4; 1.1 to 1.7). Among women with bacterial vaginosis, the highest risk of preterm delivery of a low-birth-weight infant was found among those with both vaginal bacteroides and Mycoplasma hominis (odds ratio, 2.1; 95 percent confidence interval, 1.5 to 3.0). CONCLUSIONS: Bacterial vaginosis was associated with the preterm delivery of low-birth-weight infants independently of other recognized risk factors.

Cohort Studies↗

Breath-hold 3D STAR MR angiography of the renal arteries using segmented echo planar imaging.

Three-dimensional (3D), cardiac triggered renal MR angiograms were acquired with excellent background suppression within a single breath-hold of 18 to 30 s using signal targeting with alternating radiofrequency (STAR), a subtraction time-of-flight MR angiography technique, and a 3D scheme combining echo planar imaging (EPI) readouts and k-space segmentation. The 3D STAR sequence was evaluated on 17 healthy individuals, 3 potential renal donors, and 2 patients with suspected renovascular hypertension. An inversion tag through the aorta was applied to produce the vascular contrast. After a suitable inflow time, 16 to 64 sections were encoded. An additional presaturation pulse applied over the imaging volume prior to tagging permitted improved background suppression by reducing signal variations from involuntary motion and changes in the cardiac period during breath-holding. Intrarenal branches were observed consistently in all healthy individuals. Longer inflow times provided better depiction of the intrarenal vessels while shorter delays delineated the proximal renal branches with better signal-to-noise ratio. Breath-hold and diastolic data collection reduced both blurring and flow related dephasing. Our results demonstrate excellent visualization of the renal arteries to the level of intrarenal branch vessels using the proposed technique.

Adult↗

Activation of association auditory cortex demonstrated with functional MRI.

Activations in the temporal lobes previously observed using positron emission tomography and auditory stimuli were partially reproduced with functional MRI and echo-planar imaging at 1.5 T in six volunteers performing tone and phoneme monitoring tasks. Verbal processing compared to a tone recognition task significantly activated a cortical area located in the left anterior temporal region (P < 0.02).

Adult↗

Initial clinical studies of CVD 112 Vibrio cholerae O139 live oral vaccine: safety and efficacy against experimental challenge.

Since October 1992, epidemics of cholera associated with Vibrio cholerae O group 139 have occurred in India, Bangladesh, and much of the rest of Asia. A volunteer model was used to determine the safety, immunogenicity, and efficacy of an attenuated delta ctxA delta zot delta ace delta cep V. cholerae O139 vaccine strain, designated CVD 112. Six volunteers received 10(6) cfu and 6 received 10(8) cfu of CVD 112. No subject who received the 10(6) dose had diarrhea or other severe symptoms after vaccination; 3 vaccinees developed mild diarrhea (mean stool volume, 648 mL) after receiving the higher dose. Five weeks after vaccination, 8 vaccinees and 15 unvaccinated control subjects underwent challenge with 10(6) cfu of wild type V. cholerae O139 AI1837. One vaccinee (13%) and 12 control subjects (80%) developed diarrhea after challenge (P = .003). The short-term protective efficacy conferred by vaccine strain CVD 112 was 84% and was remarkably similar to that conferred by primary wild type clinical infection (80%).

Administration, Oral↗

Enteral immunization and challenge of volunteers given enterotoxigenic E. coli CFA/II encapsulated in biodegradable microspheres.

The development of a safe and effective vaccine against enterotoxigenic Escherichia coli (ETEC) would be useful for travellers and for young children in endemic areas. A feasibility study of an enteral ETEC vaccine prototype consisting of colonization factor antigen II (CFA/II), containing two component antigens CS1 and CS3, encapsulated in biodegradable polymer microspheres (BPM) was conducted in healthy volunteers. Ten adult volunteers swallowed intestinal tubes on days 0, 7, 14 and 28; after collection of jejunal fluid samples, 1 mg of CFA/II in BPM was administered via the tube. Volunteers kept a diary of symptoms after each dose. Secretory IgA in jejunal fluids, serum responses and circulating antibody-secreting cells (ASC) were measured before and after vaccination. The vaccine was well tolerated. Five of ten volunteers developed IgA anti-CFA/II ASC by 7 days after the last dose of vaccine; these same five vaccinees had IgA anti-CS3 ASC, and three of these five vaccinees had IgA anti-CS1 ASC. Five of ten vaccinees developed rises in jejunal fluid sIgA anti-CFA/II with peak GMT of 1:42. About 8 weeks after the first dose of vaccine, ten vaccinees and ten unvaccinated control volunteers underwent challenge with 10(9) c.f.u. ETEC E24377A (O139:H28 LT+ST+CS1+CS3+). Ten of ten controls and seven of ten vaccinees developed diarrhoea (p = 0.11, 30% vaccine efficacy). Two of the three protected vaccinees had the highest numbers of ASC and highest sIgA titres during the course of immunization, suggesting that these responses were protective and that this vaccine development strategy has merit. Future studies with higher dosages and a different dosing schedule are planned.

Adult↗

Phase 1 trial of a 24-valent Klebsiella capsular polysaccharide vaccine and an eight-valent Pseudomonas O-polysaccharide conjugate vaccine administered simultaneously.

A Klebsiella (K) vaccine consisting of 24 capsular polysaccharide antigens and a Pseudomonas aeruginosa (P) vaccine consisting of eight O-polysaccharide antigens conjugated to P toxin A have been developed to prevent sepsis by means of active or passive immunoprophylaxis. In search for a practical immunization schedule, the two vaccines were injected in opposite arms simultaneously (20 volunteers) or 14 days apart (21 volunteers). The vaccines were similarly well tolerated by both volunteer groups. Geometric mean antibody concentrations and mean fold antibody rises to the 33 vaccine antigens (including toxin A) were similar in the two groups at 2 months, and the decline in antibody measured at 18 months was also similar. Because the two vaccines were safe and similarly immunogenic in the two vaccine groups, they can be administered simultaneously to patients or plasma donors in a practical vaccination schedule.

Adolescent↗

Quantitative relationship between oral temperature and severity of illness following inoculation with candidate attenuated dengue virus vaccines.

The relationship between oral temperature and other parameters of illness was examined in 51 adult volunteers who were inoculated experimentally with partially attenuated candidate dengue virus vaccines. In subjects who developed clinical illness, the peak illness temperature, mean illness temperature, and peak 6:00 A.M. illness temperature all correlated positively with the total number of signs and symptoms other than fever and with a fall in the white blood cell count (the latter was the only laboratory abnormality significantly associated with clinical illness [P = .02]). Of these factors, the peak 6:00 A.M. oral temperature exhibited the strongest correlations with the two parameters used to estimate severity of illness (rxy = .58 and P < .01 for signs and symptoms; rxy = .37 and P = .01 for fall in white blood cell count).

Adolescent↗

A live attenuated dengue-1 vaccine candidate (45AZ5) passaged in primary dog kidney cell culture is attenuated and immunogenic for humans.

A dengue-1 candidate vaccine (45AZ5), previously found to be underattenuated in 2 volunteers, was further attenuated by passage in primary dog kidney (PDK) cell cultures. New candidate vaccines prepared from three levels of PDK-passaged virus, PDK-10, PDK-20, and PDK-27, were each injected into 9 or 10 volunteers. There was a significant, progressive decline in viremia, clinical illness, and hematologic changes from low to high PDK cell passage level. PDK-20 infected all 10 vaccinees and induced viremia in 5, transient fever in 3, symptoms that resulted in curtailed activities for < or = 1 day in 4, and neutralizing antibody in all 10, which persisted for > or = 1 year in 5 of 8 vaccinees tested. Progressive passage in PDK cell culture progressively attenuates vaccine candidate strain 45AZ5 for humans. Because passage level PDK-20 may be suitable for healthy adults at high risk of dengue fever, additional clinical trials of this strain are warranted.

Adolescent↗

Cytokine production patterns and lymphoproliferative responses in volunteers orally immunized with attenuated vaccine strains of Salmonella typhi.

New recombinant strains of attenuated Salmonella typhi used as live oral vaccines elicit potent immune responses. This study examined the patterns of cytokine production and proliferation to specific S. typhi antigens in subjects orally immunized with attenuated S. typhi vaccines CVD 906, CVD 908, and CVD 908 expressing the circumsporozoite protein of Plasmodium falciparum. After immunization, sensitized lymphocytes were found in subjects' blood that exhibited significantly increased proliferative responses and interferon-gamma production to purified S. typhi flagella when compared with preimmunization levels. Significant negative correlations were observed between interleukin-4 production and both interferon-gamma production and proliferation to S. typhi flagella. These results demonstrate that oral immunization with attenuated S. typhi strains alone or with those carrying a foreign gene elicits strong systemic cell-mediated immunity to purified S. typhi antigens, including the production of cytokines compatible with T1-type responses.

Animals↗

Safety, immunogenicity, and efficacy of a malaria sporozoite vaccine administered with monophosphoryl lipid A, cell wall skeleton of mycobacteria, and squalane as adjuvant.

A Plasmodium falciparum circumsporozoite protein (PfCSP) recombinant fusion protein, R32NS1(81), formulated with monophosphoryl lipid A, cell wall skeleton of mycobacteria, and squalane (Detox) was administered to 12 volunteers. One volunteer had malaise and self-limited painful induration at the injection site after the second dose and declined further immunization. The other 11 volunteers tolerated the three doses of 1,230 micrograms of vaccine, but most complained of sore arms; in five cases the pain or malaise was severe enough to interfere with work or sleep. Two weeks after the third dose of vaccine, four of the 11 immunized volunteers had > or = 14 micrograms/ml of antibodies to the repeat region of the PfCSP in their serum. Two of these four volunteers did not develop P. falciparum parasitemia when challenged by the bite of five mosquitoes carrying P. falciparum sporozoites. The seven volunteers with lower levels of antibodies and 11 of 11 controls developed parasitemia. These data are consistent with other studies, and indicate that vaccine-induced antibodies against the repeat region of PfCSP can prevent effective sporozoite infection of hepatocytes in humans. The challenge is to improve the immunogenicity of PfCSP-based vaccines, and to develop methods for including PfCSP peptides as components of multitarget malaria vaccines.

Adjuvants, Immunologic↗

CD4+ T cell clones obtained from Plasmodium falciparum sporozoite-immunized volunteers recognize polymorphic sequences of the circumsporozoite protein.

CD4+ T cell clones were derived from three volunteers who were protected against malaria after immunization with Plasmodium falciparum sporozoites. T cells specific for an epitope, Pf Th/Tc, contained in amino acids 326 to 345 of the circumsporozoite (CS) protein of P. falciparum (NF54) were derived from all three volunteers. DR1-, -4-, -7-, and -9-restricted T cell clones were found to recognize overlapping, but distinct, epitopes within a 20-mer peptide representing the amino acid 326 to 345 sequence. The Pf Th/Tc epitope contains part of the highly conserved region II as well as part of a polymorphic domain of the P. falciparum CS protein. All of the overlapping epitopes within peptide 326-345 contained at least three amino acids of the amino terminus of the conserved region II, in addition to a variable number of amino acids in the polymorphic region. The DR4-, -7-, and -9-restricted but not the DR1-restricted T cell clones recognized variant peptides representing this polymorphic region of the CS protein of P. falciparum isolates from Africa, Asia, and South America.

Alleles↗

Immunization of rabbits with enterotoxigenic E. coli colonization factor antigen (CFA/I) encapsulated in biodegradable microspheres of poly (lactide-co-glycolide).

We have searched for an effective oral delivery system for a purified enterotoxigenic Escherichia coli (ETEC) fimbrial adhesin, CFA/I, which elicits anti-colonization immunity. Purified CFA/I antigen encapsulated in biodegradable polymer microspheres of poly (DL-lactide-co-glycolide) (PLG) induced a vigorous, systemic CFA/I IgG antibody response in rabbits immunized once via intragastric tube; oral, unencapsulated CFA/I induced little or no circulating antibody. CFA/I-specific, S-IgA coproantibody was detected in one of three rabbits fed with the CFA/I-PLG microsphere vaccine. We conclude that PLG microspheres protected CFA/I from degradation in the stomach and effectively delivered the antigen for processing by the host's immune system.

Adhesins, Escherichia coli↗