The hemagglutination inhibition antibody responses to an inactivated influenza vaccine among healthy adults: with special reference to the prevaccination antibody and its interaction with age

The immunogenicity of the trivalent split-virus influenza vaccine was investigated among 70 healthy adults (mean age: 48.5, range: 36-68). The vaccine antigens were: A/Yamagata/32/89 (H1N1); A/Beijing/352/89 (H3N2); and B/Bangkok/163/90. Regarding the entire sample, the vaccine induced a tenfold or more rise on the average in the hemagglutination inhibition (HAI) antibody to each antigen. The response rates (greater than or equal to a fourfold rise) were about 90% or more among those with a prevaccination titer < or = 1:64 (equivalent to < or = 1:16 on the Western scale; in Japan, the HAI titers are expressed by the final, and not the initial, dilution of the serum; from hereon our findings will be expressed using the Japanese scale), whereas they were 0-50% at > or = 1:128. Thus, the prevaccination titer was negatively associated with antibody induction. The achievement rates (postvaccination titer > or = 1:128) among those with a prevaccination titer < 1:16 remained at 48-68%. Regarding the analysis of variance, a significant effect on antibody induction was indicated for the prevaccination titer (P < or = 0.002), but not for age (P > or = 0.425). The interaction between the prevaccination titer and age was significant for A/Yamagata (P = 0.030), while it was also suggestive for A/Beijing (P = 0.054): as age increased, those with no preexisting antibody (< 1:16) showed greater titer rises, in contrast to the smaller rises among those with a titer > or = 1:16. Based on the attack survey conducted separately, the vaccine efficacy on influenza-like illnesses with fever < or = 37 degrees C and > or = 37.5 degrees C was calculated to be 16% (95% confidence interval: -66% to 57%) and 37% (-55% to 74%), respectively.     

Helper and cytotoxic T lymphocyte responses to influenza vaccination in healthy compared to diabetic elderly

This study was designed to determine the effect of Type II diabetes mellitus in older adults on two measures of the cell-mediated immune response to influenza vaccination. Twenty-two elderly persons with diabetes mellitus were compared to 20 healthy seniors, all of whom were living independently in the community. Peripheral blood mononuclear cells (PBMC) were challenged in vitro with live influenza virus, pre-vaccination and 4 and 12 weeks post-vaccination. PBMC culture supernatants were assayed for IL-2 activity as a measure of the helper T-cell response to vaccination. The cytotoxic T-lymphocyte response was determined using an assay of granzyme B activity in PBMC lysates. Initial analysis of the data showed increased IL-2 production in post-vaccination PBMC cultures from the diabetic group compared to the healthy group. However, when vaccination histories were used in an analysis of variance, it was found that the difference between the two groups was related to vaccination history. Study subjects vaccinated one year prior to participation in this study compared to those who had not been previously vaccinated, demonstrated a significantly suppressed IL-2 response to vaccination. Type II diabetes mellitus had no effect on the IL-2 response to vaccination. The granzyme B response to vaccination was not significantly affected by previous vaccination and results were similar for the healthy and diabetic elderly groups.     

Intestinal immune responses to an inactivated oral enterotoxigenic Escherichia coli vaccine and associated immunoglobulin A responses in blood

An inactivated oral enterotoxigenic Escherichia coli (ETEC) vaccine against ETEC diarrhea was given to 25 adult Swedish volunteers. The vaccine consisted of formalin-killed E. coli bacteria expressing the most common colonization factor antigens (CFAs), i.e., CFA/I, -II, and -IV, and recombinantly produced cholera B subunit (CTB). Immunoglobulin A (IgA) antibody responses in intestinal lavage fluid to CTB and CFAs were determined and compared with corresponding responses in stool extracts and serum as well as with IgA antibody-secreting cell (ASC) responses in peripheral blood. Two doses of vaccine induced significant IgA responses to the different CFAs in lavage fluid in 61 to 87% of the vaccinees and in stool in 38 to 81% of them. The most frequent responses were seen against CFA/I. The magnitudes of the antibody responses against CTB and CFA/I in stool correlated significantly (CTB, P < 0.01; CFA/I, P < 0. 05) with those in intestinal lavage. Intestinal lavage responses against CFAs were best reflected by the ASC responses, with the sensitivity of the ASC assay being 80 to 85%, followed by stool (sensitivity of 50 to 88%) and serum antibody (sensitivity of 7 to 65%) analyses. CTB-specific immune responses were seen in >90% of the vaccinees in all assays.     

Sex hormone responses in healthy men and male patients with chronic obstructive pulmonary disease during an oral glucose load

The responses of serum testosterone, sex hormone-binding globulin (SHBG) and luteinizing hormone (LH) to an oral glucose tolerance test (OGTT) were investigated in 16 healthy subjects as well as in 11 normoxaemic and 10 hypoxaemic chronic obstructive pulmonary disease (COPD) patients. The latter group were investigated on two occasions, with and without oxygen therapy. Testosterone and apparent free testosterone concentration (AFTC) fell significantly in the healthy subjects as well as in the hypoxaemic patients on oxygen therapy (p < 0.01), whereas LH increased in all groups during the OGTT (p < 0.05). There were significantly higher SHBG levels (p < 0.01), and lower AFTC levels (p < 0.05) in the hypoxaemic group compared to the healthy subjects. In the hypoxaemic group short-term oxygen therapy increased basal AFTC significantly (p < 0.05). With oxygen therapy, the 120-min glucose levels fell significantly from 9.1 +/- 3.2 to 7.6 +/- 2.7 mmol l-1 (mean +/- SD) in the hypoxaemic group (p < 0.05). In conclusion, we have found the serum testosterone and AFTC levels to decrease after an oral glucose load in healthy subjects, together with a compensatory increase in LH. The same pattern is seen in COPD patients. The hypoxaemic patients have a reduced AFTC which is partly reversed by oxygen therapy.     

Comparison of the safety, tolerability, and immunogenicity of a MF59-adjuvanted influenza vaccine and a non-adjuvanted influenza vaccine in non-elderly adults

The adjuvanted influenza vaccine FLUAD is composed of subunit influenza antigens combined with the MF59-adjuvant emulsion. The vaccine was developed primarily for use in elderly populations, but non-elderly individuals might also benefit. To evaluate this hypothesis, 301 healthy adults were assigned randomly to receive two intramuscular injections of either FLUAD (150 subjects) or a non-adjuvanted vaccine, Fluzone (151 subjects), in two trials conducted at a 1-year interval. Injections consisted of 15 micrograms per 0.5 ml dose. Vaccine composition was A/Texas/36/91 (H1N1), A/Johannesburg/33/94 (H3N2), and B/Harbin/7/94 for the first injection and A/Texas/36/91 (H1N1), A/Nanchang/933/95 (H3N2), and B/Harbin/7/94 for the second injection. Immunogenicity was evaluated at 28 and 180 days post-immunization. FLUAD was generally well tolerated in healthy adults when compared with Fluzone. FLUAD was associated with increased pain at the injection site after immunization. A statistically significant increase in the incidence of injection-site warmth, chills, myalgia, and analgesic/antipyretic use occurred in the FLUAD group after the first injection but not after the second injection. In both groups, most of these local and systemic reactions were classified as mild. FLUAD was more immunogenic than Fluzone following both injections. After the first injection, statistically significant differences were found in the percentage of subjects with four-fold rises in hemagglutinin inhibition (HI) titers at 28 days post-immunization for the B antigen. After the second injection, the FLUAD group had significantly higher HI titers, a significantly higher percentage with a four-fold increase in titer, and a significantly greater percentage of subjects with titers >/=160 for the H3N2 antigen at 28 days. Only minor immunogenicity differences between the two groups were seen at 180 days. Compared with Fluzone, FLUAD was associated with increased immunogenicity and mild post-immunization reactions in healthy adults. The magnitude of increased immunogenicity in healthy adults was less than that seen in elderly populations.     

Training to criterion in eyeblink classical conditioning in Alzheimer's disease, Down's syndrome with Alzheimer's disease, and healthy elderly.

The cholinergic antagonist scopolamine delays acquisition of eyeblink classical conditioning (EBCC) in rabbits and humans, but scopolamine-treated organisms eventually acquire conditioned responses (CRs). Patients with probable Alzheimer's disease (AD) and older adults with Down's syndrome (DS/AD) have disrupted cholinergic systems and perform EBCC very poorly. It was hypothesized that patients with probable AD and DS/AD, like scopolamine-injected organisms, would acquire CRs if given sufficient training. Twelve probable AD patients, 12 DS/AD patients, and 6 healthy elderly control individuals participated in 5 daily 90-trial sessions of EBCC. Fifty-eight percent of the probable AD, 92% of the DS-AD, and 100% of the control participants achieved learning criterion. Probable AD, DS/AD, and control participants had statistically significant increases in the percentage of CRs produced over 5 EBCC sessions. The neural substrate for EBCC was not eliminated in probable AD or DS/AD patients, although the learning mechanism was disrupted. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Clinical and in situ cellular responses to Haemophilus ducreyi in the presence or absence of HIV infection

This study examined the prevalence of cardiovascular risk factors among low-income women and assessed the level of awareness and attitudes about these risk factors in the community. A survey instrument was developed and administered by a single researcher to a convenience sample of women in health clinics and nonclinical community settings. These settings included: an academic clinic, community clinics, women's shelters, free meal sites, community centers, public housing units, and private homes in Philadelphia, Pennsylvania. Two hundred two women were selected without regard to age or race. The mean number of cardiovascular risk factors per subject was 2.6 (SD 1.4). Each of eight established cardiovascular risk factors was identified by 4% to 34% of subjects. Among those women with a specific risk factor, only 0% to 45% reported that they were at increased risk due to the presence of that factor. The prevalence of cardiovascular risk factors among low-income women is substantial. Knowledge and understanding of these risk factors is suboptimal, particularly among women personally affected by risk factors for cardiovascular disease.     

A 6-month comparison between formoterol and salmeterol in patients with reversible obstructive airways disease

The aim of this randomized, open, parallel group study was to compare the clinical efficacy of formoterol dry powder capsule 12 micrograms b.i.d. and salmeterol dry powder 50 micrograms b.i.d. in the treatment of patients with reversible obstructive airways disease. The 6-month treatment was preceded by a 2 week run-in period. Morning pre-dose peak expiratory flow (PEF) during the last 7 days of treatment was the primary variable. Throughout the study, patients recorded morning and evening pre-dose PEF, use of rescue medication, respiratory symptoms and adverse events. Clinic visits were scheduled at monthly intervals. Of the 482 patients randomized (equal numbers in the two treatment groups), 428 completed the study. Four hundred and twenty-five patients were included in the efficacy analysis for the primary variable. For mean morning pre-dose PEF during the last 7 days of treatment, the 95% confidence interval (CI) for the treatment contrast formoterol minus salmeterol was included entirely in the pre-defined range of equivalence (CI limits = -8.69, +9.841 min-1). This was also the case for the morning PEF during the last week before each clinic visit. For mean evening pre-dose PEF, the estimated treatment contrasts showed a trend towards superiority of formoterol over salmeterol, which became statistically significant at 2, 3 and 4 months (P < 0.05; estimated contrasts 7.27, 10.45 and 10.511 min-1, respectively). No treatment group differences were found in use of rescue medication and respiratory symptom scores. The incidence of adverse events was similar in the two groups. These findings demonstrate that formoterol 12 micrograms b.i.d. and salmeterol 50 micrograms b.i.d., both formulated as dry powders, have similar long-term efficacy and safety profiles in patients with reversible obstructive airways disease.     

Combined nicotinic and muscarinic blockade in elderly normal volunteers: cognitive, behavioral, and physiologic responses

1-, 3-, and 6-nitrobenzo[a]pyrene (nitro-BaP) are environmental contaminants that can be metabolized to genotoxic derivatives by either nitroreduction or ring-oxidation. In this study, we examined the types of mutations produced by the primary nitroreduced metabolites, 1-, 3-, and 6-nitroso-BaP (NO-BaP) in the hprt gene of Chinese hamster ovary cells. RNA from 6-thioguanine-resistant mutants was reverse-transcribed to cDNA and the hprt coding sequence was amplified and sequenced. The mutational patterns produced by the three compounds exhibited extensive similarities: 1) base pair substitutions accounted for 67% (28/42) of 1-NO-BaP, 51% (26/51) of 3-NO-BaP, and 50% (11/22) of 6-NO-BaP mutations; 19-36% of the mutations were exon deletions and 14-18% were frameshifts; 2) most (64-84%) of the simple base pair substitutions occurred at G:C, mainly G:C-->T:A and G:C-->C:G transversions; 3) 98% (46/47) of the simple base pair substitutions at G:C had the mutated dG on the non-transcribed strand and 81% (38/47) were located with the mutated dG flanked 3' by at least one purine; and 4) most simple base pair substitutions (48/62, 77%) occurred in exons 2, 3, and 8 of the hprt gene. Although there were no significant differences among the mutation profiles of the NO-BaPs, a significant difference did exist between the mutation pattern produced by 3-NO-BaP and the mutation pattern previously determined for the ring-oxidized product of 3-nitro-BaP metabolism, trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9, 10-tetrahydro-3-nitrobenzo[a]pyrene. This observation indicates that differences in the structures of closely related adducts can be important enough to have an effect on mutation profiles.     

Lexical effects and lexical properties associated with National Adult Reading Test (NART) stimuli in healthy young adults and healthy elderly adults

Among patients with hepatic iron overload, the distinction between hereditary hemochromatosis (HH), a common yet treatable genetic disease, and other causes of siderosis remains problematic. The recent discovery of a specific homozygous mutation (C282Y) in a novel major histocompatibility complex class I-like gene (named HLA-H or HFE) in 80% to 100% of well-characterized cases of HH suggests that direct DNA-based mutation analysis may help resolve this dilemma. To assess the clinical utility of direct HLA-H mutation analysis in a typical diagnostic setting, we measured genotypic and phenotypic parameters of iron overload in 37 subjects with biopsy-proven hepatic siderosis (2+ or greater) and in 127 healthy control subjects. The prevalence of C282Y homozygotes was significantly greater in the hepatic siderosis group (32%) than in the control group (0%), confirming the association between this homozygous mutation and hepatic iron overload. In the hepatic siderosis group, C282Y homozygotes had significantly higher hepatic iron and ferritin levels, a significantly lower prevalence of hepatitis C virus or alcoholic liver disease, but no significant difference in the saturation of serum transferrin. Of the 20 subjects with a hepatic iron index (HII) in the previously defined "hemochromatosis range" (>1.9), 9 (45%) were C282Y homozygotes. Of the 11 nonhomozygous subjects with an HII greater than 1.9 (presumed false-positive HIIs), 10 (91%) had hepatic cirrhosis compared with 3 of 9 (33%) homozygotes with an HII greater than 1.9 who had cirrhosis (P<.02). The HII thus has poor diagnostic specificity for predicting genotypic HH in patients with cirrhosis. We conclude that direct determination of the HLA-H C282Y genotype may be the single best diagnostic test for HH, particularly in patients with cirrhosis, for whom the HII is quite nonspecific.     

Effects of smoking on renal hemodynamics in healthy volunteers and in patients with glomerular disease

Patients with renal disease who smoke have a poor renal functional prognosis, but the mechanisms involved have not been explored. In this controlled study, the effects of smoking and sham smoking were compared in 15 healthy normotensive volunteers. All were occasional smokers and abstained from smoking for 48 h as documented by urinary cotinine measurements. These data were compared with those of seven patients with biopsy-confirmed IgA glomerulonephritis, also occasional smokers. Renal clearance examinations were obtained after hydration in the supine position before and while smoking two cigarettes or sham cigarettes in random order on 2 consecutive days. GFR and effective renal plasma flow were determined using In111-diethylenetriamine penta-acetic acid and 131I-hippurate with a dual tracer infusion clearance technique. In an ancillary study with six volunteers, the effect of smoking was compared with the effect of nicotine-containing chewing gum. In healthy volunteers, sham smoking caused a minor but significant increase of mean arterial pressure (MAP) and GFR with no significant change of effective renal plasma flow, filtration fraction (FF), or renovascular resistance. Smoking caused a significant and more marked increase of MAP (from baseline 92.8+/-8.98 to 105+/-7.78 mmHg) and heart rate (from 61.7+/-7.52 to 86.4+/-9.87 min(-1)), accompanied by a significant increase in arginine vasopressin (from 1.27+/-0.72 to 19.9+/-27.2 pg/ml) and epinephrine (from 37+/-13 to 140+/-129 pg/ml). During smoking, GFR decreased in all but one volunteer (from 120+/-17.7 to 102+/-19.3 ml/min per 1.73 m2), and this was accompanied by a significant decrease of FF (from 21.3+/-4.24 to 17.4+/-3.41%) and an increase in renovascular resistance (from 97.6+/-27.2 to 108+/-30.4 mmHg x min/ml per 1.73 m2). These findings were reproduced with nicotine-containing chewing gum. In contrast, when patients with IgA glomerulonephritis smoked, a similar increment in MAP was noted, the changes of FF were not uniform, and a small but consistent increase of urinary albumin/creatinine ratio was observed. An additional 20 volunteers were subjected to the smoking arm of the study for statistical evaluation of the GFR change in patients. The difference between the change of GFR between all volunteers (n = 35) and patients (n = 7) was significant (P < 0.005). It is concluded that the known effects of smoking and nicotine on the sympathetic nervous system and on systemic hemodynamics are accompanied by significant acute changes in renal hemodynamics and albuminuria. These findings are of interest because of the known effects of smoking on progression of renal disease.     

Polyarthropathy, orbital myositis and posterior scleritis: an unusual adverse reaction to influenza vaccine

We report a patient who developed an acute symmetrical polyarthropathy, orbital myositis and posterior scleritis following inoculation with the 1993 Fluvirin (inactivated influenza vaccine: surface antigen) vaccine. We believe that this represents a hypersensitivity reaction to the vaccine as extensive investigations revealed no underlying infective, inflammatory or systemic cause. We review the current indications for vaccination against the influenza virus and the known adverse reactions to the vaccine.     

Effects of air pollution on symptoms and peak expiratory flow measurements in subjects with obstructive airways disease

In preterm neonates, intraventricular haemorrhage is linked to the dysfunction of cerebral autoregulation (AR). We aimed at tracing the critical closing pressure (CCP) in order to quantify AR and to reveal its inner workings. In an observational study, 10 preterm neonates (median, range: ga 28 weeks, 25 to 32 weeks; bw 1070, 685 to 1730 g; age 2d, 1 to 7 d) were continuously Doppler traced (a. carotis interna) for > 10 min. Systemic blood pressure (BP, a. umbilicalis, a. radialis, a. temporalis) was recorded simultaneously (> 1200 cardiac cycles each). Systolic BP was on average 11 mmHg above CCP. There was a striking parallel between both variables, even in cases of sudden spontaneous BP fluctuations > 30% (r = 0.72, 0.41 to 0.99), while systolic cerebral blood flow velocity remained largely unaffected (r = -0.15, -0.75 to 0.53), indicating a properly functioning AR. CCP was 28 mmHg, 14 to 38 mmHg. Based on our data, a physiological model of AR is developed, integrating anatomy, metabolic and neuronal pathways with former physiologic findings--including low frequency cycling of cerebral blood flow velocity. Tracing of CCP is thought to have the potential to identify infants with impaired AR. Since this method is noninvasive and independent of angle of insonation (thus rendering it uncritical in probe fixation), it is a promising tool for sustained monitoring of cerebral haemadynamics in the clinical setting.     

Clinical and serological study of tsutsugamushi disease in northern Osumi, Kagoshima Prefecture

We report 34 cases of tsutsugamushi disease seen from 1989 to 1993 at Yagi Clinic, northern Osumi, Kagoshima Prefecture. Nineteen patients (55.9%) showed the highest antibody titers against the Kawasaki strain Orientia tsutsugamushi (Ot) and 13 (38.2%) against the Kuroki strain Ot. It is suggested that two antigenic types (Kawasaki and Kuroki) of Ot were distributed in Kagoshima Prefecture, and the Kawasaki type Ot more or less dominates Kuroki type Ot. There was no difference in clinical features between the two groups of patients.     

Patterns of hospitalization in elderly patients with asthma and chronic obstructive pulmonary disease

The purpose of this study was to describe the impact of asthma and chronic obstructive pulmonary disease (COPD) in the elderly on health care utilization. The Health Care Financing Administration (HCFA) file for the year 1984 through 1991 involving beneficiaries < or = 65 yr were searched for the diagnoses of asthma and COPD by ICD-9 codes. The study groups were created by determining the first admission for an exacerbation of either disease during each year from 1984 through 1991. Patients were identified by their social security number. The 1984 cohort consisted of 56,692 patients with asthma exacerbation and 162,899 with COPD exacerbation. The 1991 cohort consisted of 67,758 patients with asthma exacerbation and 131,974 patients with COPD exacerbation. In addition, the 1984 cohort was tracked by social security number for evidence of rehospitalization for either asthma or COPD through 1991. Length of hospitalization increased as patients grew older. The discharge rate to an independent living facility diminished as age increased. The use of convalescent and nursing homes or home health care after discharge more than doubled from 1984 through 1991. The utilization of health care resources by elderly patients with asthma and COPD is immense, both during hospitalization and after discharge.     

Intraindividual variability in cognitive performance in older adults: Comparison of adults with mild dementia, adults with arthritis, and healthy adults.

Intraindividual variability in latency and accuracy of cognitive performance across both trials and occasions was examined in 3 groups of older adults: healthy adults, adults with arthritis, and adults diagnosed with mild dementia. Participants completed 2 reaction-time and 2 episodic-memory tasks on 4 occasions. Results indicated that intraindividual variability in latency was greater in individuals diagnosed with mild dementia than in adults who were neurologically intact, regardless of their health status. Individual differences in variability were stable over time and across cognitive domains. Intraindividual variability was also related to level of performance and was uniquely predictive of neurological status, independent of level of performance. Results suggest that intraindividual variability may be a behavioral indicator of compromised neurological mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Antibody and clinical responses in volunteers to immunization with malaria peptide-diptheria toxoid conjugates

Twenty residue peptides from the 185-200-kD and 45-kD merozoite surface antigens of the malaria parasite Plasmodium falciparum were covalently linked to diphtheria toxoid as a carrier and used to immunize human volunteers with aluminium hydroxide as an adjuvant. Significant antibody levels were elicited by two boosting injections. The antibodies reacted with acetone-methanol fixed merozoite membranes in an immunofluorescence assay, but no inhibition of merozoite reinvasion could be detected in in vitro cultures containing the antibodies. Antibody levels against the immunizing peptides declined markedly within 77 days after the third injection. No hypersensitivity was observed against the peptides. However, the volunteers developed hypersensitivity against diphteria toxoid, and in particular a pronounced type III (Arthus) hypersensitivity after three injections with the toxoid. This effect might appear to limit the use of peptide-diphtheria toxoid conjugates for human immunization. Several biochemical, haematological and immunological tests done on the volunteers showed no other adverse effects from the immunizations.