Prevalence and characteristics of diagnostic groups amongst 1034 patients seen in ENT practices for dizziness.

OBJECTIVE: To determine the prevalence and characteristics of various diagnostic groups amongst patients referred to ENT practices with the primary complaint of dizziness. STUDY DESIGN: A prospective, observational, multicentre study. METHODS: Consecutive patients presenting with dizziness to the participating ENT practices were enrolled. Seven ENT specialists at three clinics participated. RESULTS: Benign paroxysmal positional vertigo was diagnosed in 53.3 per cent of the 1034 study patients. Fifty-nine per cent of these experienced night-time awakening with dizziness, which was a significant proportion in comparison to the other diagnostic groups. Benign paroxysmal positional vertigo was the most frequent diagnosis in all age groups, including those over 70 years. CONCLUSION: In this study of patients referred to ENT for dizziness, benign paroxysmal positional vertigo was the dominant diagnostic entity, in all age groups and overall. All clinicians in contact with dizzy patients must consider benign paroxysmal positional vertigo, especially in the elderly.

Viral fitness implications of variation within an immunodominant CD8+ T-cell epitope of HIV-1.

Cytotoxic T-lymphocyte (CTL) epitopes within the HIV genome are subject to negative and positive selective pressures, the balance of which influences CTL escape at a given epitope. We investigated whether viral fitness requirements dictate conservation of the HLA-A2 restricted immunodominant epitope SLYNTVATL (SL9). Viral clones incorporating changes throughout the SL9 epitope region were compared to consensus SL9 virus in terms of replication kinetics and relative viral fitness. Constructs recapitulating in vivo SL9-CTL escape variants showed markedly little effect on replication and fitness, as did non-natural conservative mutations targeting immunologically relevant positions of the epitope. Although certain residues of the epitope were constrained by viral requirements, our research reveals that there are multiple SL9 variants that are well tolerated virologically but fail to arise in vivo. In light of this data, assumptions regarding the balance of immune and viral selective pressures on this immunodominant epitope sequence need to be reassessed.

[Visual circle scale (VCS)--a patient-friendly scale to measure pain compared to VAS and Likert scale]. / Visuelle Kreisskala (VCS)--eine patientenfreundliche Skala zur Schmerzmessung im Vergleich mit der VAS und Likert-Skala.

AIM: The visual analogue scale (VAS) and Likert scale (LS) are widely used but the patients might have difficulties to work with these scales and there might be errors in calculation. The visual circle scale (VCS) is a graphic construct with a simple grading to augment the understanding and ease for calculation. METHOD: This study compares the different scales in orthopaedic patients for pain assessment postoperatively. In addition, the scales were rated by the patients for simplicity, understanding and global rating. RESULTS: Included were 65 patients (40 women) with an average age of 66 years with 330 pain assessments and 65 questionnaire ratings. The average pain was LS 42.7, VAS 39.3, VCS 44. The correlation coefficients r (Spearman) between all scales were > 0.89 and the same held also for sensitivity for change. The VCS was the scale preferred by > 50 % of the orthopaedic patients to assess the pain. CONCLUSION: The VCS is able to measure pain comparably to the known scales (VAS, Likert scale). From the patients point of view it is the preferred scale to work with.

Quantitative and qualitative assessment of human immunodeficiency virus type 1 (HIV-1)-specific CD4+ T cell immunity to gag in HIV-1-infected individuals with differential disease progression: reciprocal interferon-gamma and interleukin-10 responses.

The human immunodeficiency virus type 1 (HIV-1)-specific CD4(+) T cell response was investigated in 33 untreated HIV-1-infected individuals, using highly sensitive ELISPOT assays and intracellular flow cytometry. The median frequencies of interferon (IFN)-gamma-producing HIV-1 gag-specific CD4(+) T cells did not correlate significantly with control of viral replication or progression. HIV-1 gag-specific interleukin (IL)-4-producing cells were rarely detected. Circulating frequencies of CD4(+) T cells constitutively producing IL-10, however, were significantly higher in individuals with progression or active replication. In 17 of 30 HIV-1-infected individuals, gag antigen was observed to induce IL-10 production from CD4(+) T cells. In 2 individuals, early treatment of acute HIV-1 infection "rescued" low to undetectable gag-specific IFN-gamma-producing CD4(+) T cell responses and dramatically down-regulated constitutive IL-10 production from circulating CD4(+) T cells. The detection of HIV-1-specific IL-10-inducing CD4(+) T cells in HIV-1-infected individuals suggests that HIV-1 may directly subvert specific immune responses by IL-10 induction.

Human leucocyte antigen supertypes and immune susceptibility to HIV-1, implications for vaccine design.

T cell responses against HIV-1 have been identified in a number of exposed uninfected populations. We hypothesized that the ability to mount an effective T cell response is partly determined by the human leucocyte antigens (HLA) phenotype of the individual. We examined whether certain HLA supertypes were associated with differential HIV-1 susceptibility in sexually exposed adults and in the setting of mother to child HIV-1 transmission. By multivariate analysis, decreased HIV-1 infection risk was strongly associated with possession of a cluster of closely related class I HLA alleles (A2/6802 supertype) in sexually exposed adults (Hazard ratio=0.42, 95% confidence intervals (CI): 0.22-0.81, P=0.009) and perinatally exposed infants (Odds ratio=0.12, 95% CI: 0.03-0.54, P=0.006). The alleles in this HLA supertype are known in some cases, to present the same peptide epitopes (termed 'supertopes'), for T cell recognition. The identification of HIV-1 supertopes, which are associated with protection from HIV-1 infection, has important implications for the application of epitope-based HIV-l vaccines in a variety of racial groups.

Sequence and peptide-binding motif for a variant of HLA-A*0214 (A*02142) in an HIV-1-resistant individual from the Nairobi Sex Worker cohort.

As part of the ongoing study of natural HIV-1 resistance in the women of the Nairobi Sex Workers' study, we have examined a resistance-associated HLA class I allele at the molecular level. Typing by polymerase chain reaction using sequence-specific primers determined that this molecule is closely related to HLA-A*0214, one of a family of HLA-A2 supertype alleles which correlate with HIV-1 resistance in this population. Direct nucleotide sequencing shows that this molecule differs from A*0214, having a silent nucleotide substitution. We therefore propose to designate it HLA-A*02142. We have determined the peptide-binding motif of HLA-A*0214/02142 by peptide elution and bulk Edman degradative sequencing. The resulting motif, X-[Q,V]-X-X-X-K-X-X-[V,L], includes lysine as an anchor at position 6. The data complement available information on the peptide-binding characteristics of this molecule, and will be of use in identifying antigenic peptides from HIV-1 and other pathogens.

Simian immunodeficiency virus (SIV) infection of a rhesus macaque induces SIV-specific CD8(+) T cells with a defect in effector function that is reversible on extended interleukin-2 incubation.

A vigorous expansion of antigen-specific CD8(+) T cells lacking apparent effector function was observed in a rhesus macaque acutely infected with the simian immunodeficiency virus (SIV) strain SIVmac239. Antigen-specific CD8(+) T cells were identified using antigenic-peptide class I major histocompatibility complex tetramers. As many as 8.3% of CD8(+) cells recognized the Mamu-A*01-associated SIV epitope Gag(181-189) (CTPYDINQM); however, these cells demonstrated no effector function when presented with peptide-incubated targets, as measured by intracellular cytokine staining for gamma interferon (IFN-gamma), interleukin-2 (IL-2) production, or direct cellular lysis. Similar results were observed with three other SIV peptide antigens. Nonresponsiveness did not correlate with apoptosis of the CD8(+) cells, nor were cells from this macaque impaired in their ability to present peptide antigens. Associated with the nonresponsive state was a lack of IL-2 production and decreased IL-2 receptor expression. Exogenous IL-2 treatment for 1 week in the absence of antigenic stimulation restored antigen-specific responses and the quantitative correlation between tetramer recognition and antigen-responsive IFN-gamma secretion. This case report suggests a regulatory mechanism that may impede the effector function of antigen-specific T cells during acute infection with SIV or human immunodeficiency virus in some cases. This mechanism may participate in the failure of the immune system to limit infection.

Treatment outcome after laser excision of early glottic squamous cell carcinoma--a literature survey.

Two treatment options are widely used for the cure of T1 glottic squamous cell carcinoma: radiotherapy and surgical removal. There is ongoing controversy about whether laser excision should be offered to patients with T1 glottic carcinoma. The purpose of this study is to present a review of studies dealing with treatment outcome after laser excision of T1 glottic carcinoma. Eighteen original papers on outcomes were identified. Recurrence rates ranged from 4% to 35%. The disease-specific survival rate at 5 years was found to be from 89% to 100% and crude survival from 74% to 100%. Of the six studies dealing with voice quality, radiation therapy was found to be more effective in preservation of the voice in three, while in the other three studies, no significant difference could be detected. With respect to costs of treatment, in three out of four studies laser surgery was found to be the more economical treatment option. Laser surgery seems to provide comparably low recurrence rates and high disease-specific survival as compared with radiotherapy. In T1 cancer, laser resection leaves the patient with a poorer voice quality than is the case with radiation therapy, but laser treatment seems to be the cheaper option.

Cloning and functional analysis of sucrose:sucrose 1-fructosyltransferase from tall fescue.

Enzymes of grasses involved in fructan synthesis are of interest since they play a major role in assimilate partitioning and allocation, for instance in the leaf growth zone. Several fructosyltransferases from tall fescue (Festuca arundinacea) have previously been purified (Lüscher and Nelson, 1995). It is surprising that all of these enzyme preparations appeared to act both as sucrose (Suc):Suc 1-fructosyl transferases (1-SST) and as fructan:fructan 6(G)-fructosyl transferases. Here we report the cloning of a cDNA corresponding to the predominant protein in one of the fructosyl transferase preparations, its transient expression in tobacco protoplasts, and its functional analysis in the methylotrophic yeast, Pichia pastoris. When the cDNA was transiently expressed in tobacco protoplasts, the corresponding enzyme preparations produced 1-kestose from Suc, showing that the cDNA encodes a 1-SST. When the cDNA was expressed in P. pastoris, the recombinant protein had all the properties of known 1-SSTs, namely 1-kestose production, moderate nystose production, lack of 6-kestose production, and fructan exohydrolase activity with 1-kestose as the substrate. The physical properties were similar to those of the previously purified enzyme, except for its apparent lack of fructan:fructan 6(G)-fructosyl transferase activity. The expression pattern of the corresponding mRNA was studied in different zones of the growing leaves, and it was shown that transcript levels matched the 1-SST activity and fructan content.

Zenker's diverticulum treated by the endoscopic stapling technique.

The objective of the present study is to determine whether the endoscopic stapling technique for the treatment of Zenker's diverticulum provides a relief of symptoms and an acceptably low number of complications. Previous studies have indicated that endoscopic stapling of the common wall between the oesophagus and the diverticulum is a safe and effective method that has a low complication rate and only necessitates a few days of hospitalization. To the present only a few investigations including a limited number of patients have reported the clinical outcome with regard to relief of symptoms and degree of satisfaction in a group of patients treated with this new approach. Twenty-three consecutive patients with Zenker's diverticulum treated with endoscopic staple-assisted oesophagodiverticulotomy were investigated. The median age was 70 years and the median observation time was 12 months. All patients but one (96%), reported significant relief of symptoms and 76% had no symptoms at all at the time of follow-up. In one patient, a postoperative episode of uncomplicated fever occurred, which was managed successfully with gastric tube and antibiotics. Most patients resumed oral intake of fluids and foods within the first postoperative day. The high degree of patient satisfaction, the low rate of complications and the few recurrences of symptoms reported in the present study indicate that the endoscopic stapling technique is an efficient and reliable treatment for Zenker's diverticulum.

Factors contributing to the lack of human immunodeficiency virus type 1 (HIV-1) transmission in HIV-1-discordant partners.

Correlates of resistance to infection by human immunodeficiency virus type 1 (HIV-1) are important for defining potential therapeutic interventions and for prophylactic vaccination. In this study, 11 couples discordant in their HIV-1 infection status were prospectively evaluated for the presence of protective factors. Behavioral characteristics of all subjects entailed a high risk of transmission. Cytotoxic T lymphocyte (CTL) responses against viruses isolated from the infected partner, and against laboratory virus isolates, were detected in 5 (45%) of 11 HIV-negative partners, including a CCR5Delta32-homozygous and a heterozygous subject. No CTL responses were observed in 6 control unexposed subjects. Marked variation in lymphocyte susceptibility to viral infection was noted. Resistance attributable to major histocompatibility complex discordance or anti-major histocompatibility complex antibodies was not identified. These results suggest that a combination of factors, including cellular immunity, viral characteristics, and coreceptor integrity, may be involved in the persistent nontransmission of HIV.

Influence of HLA supertypes on susceptibility and resistance to human immunodeficiency virus type 1 infection.

Certain human leukocyte antigens, by presenting conserved immunogenic epitopes for T cell recognition, may, in part, account for the observed differences in human immunodeficiency virus type 1 (HIV-1) susceptibility. To determine whether HLA polymorphism influences HIV-1 susceptibility, a longitudinal cohort of highly HIV-1-exposed female sex workers based in Nairobi, Kenya, was prospectively analyzed. Decreased HIV-1 infection risk was strongly associated with possession of a cluster of closely related HLA alleles (A2/6802 supertype; incidence rate ratio [IRR], 0.45; 95% confidence interval [CI], 0.27-0.72; P=.0003). The alleles in this supertype are known in some cases to present the same peptide epitopes for T cell recognition. In addition, resistance to HIV-1 infection was independently associated with HLA DRB1*01 (IRR, 0.22; 95% CI, 0.06-0.60; P=.0003), which suggests that anti-HIV-1 class II restricted CD4 effector mechanisms may play an important role in protecting against viral challenge. These data provide further evidence that resistance to HIV-1 infection in this cohort of sex workers is immunologically mediated.

Antisense repression of vacuolar and cell wall invertase in transgenic carrot alters early plant development and sucrose partitioning.

To unravel the functions of cell wall and vacuolar invertases in carrot, we used an antisense technique to generate transgenic carrot plants with reduced enzyme activity. Phenotypic alterations appeared at very early stages of development; indeed, the morphology of cotyledon-stage embryos was markedly changed. At the stage at which control plantlets had two to three leaves and one primary root, shoots of transgenic plantlets did not separate into individual leaves but consisted of stunted, interconnected green structures. When transgenic plantlets were grown on media containing a mixture of sucrose, glucose, and fructose rather than sucrose alone, the malformation was alleviated, and plantlets looked normal. Plantlets from hexose-containing media produced mature plants when transferred to soil. Plants expressing antisense mRNA for cell wall invertase had a bushy appearance due to the development of extra leaves, which accumulated elevated levels of sucrose and starch. Simultaneously, tap root development was markedly reduced, and the resulting smaller organs contained lower levels of carbohydrates. Compared with control plants, the dry weight leaf-to-root ratio of cell wall invertase antisense plants was shifted from 1:3 to 17:1. Plants expressing antisense mRNA for vacuolar invertase also had more leaves than did control plants, but tap roots developed normally, although they were smaller, and the leaf-to-root ratio was 1.5:1. Again, the carbohydrate content of leaves was elevated, and that of roots was reduced. Our data suggest that acid invertases play an important role in early plant development, most likely via control of sugar composition and metabolic fluxes. Later in plant development, both isoenzymes seem to have important functions in sucrose partitioning.

Very early risk stratification using combined ECG and biochemical assessment in patients with unstable coronary artery disease (A thrombin inhibition in myocardial ischemia [TRIM] substudy). The TRIM Study Group.

BACKGROUND: The diagnostic capability of troponin T (TnT), troponin I (TnI), myoglobin, and creatine kinase (CK)-MB mass for detection of myocardial injury seems evident. Newer studies have found these sensitive markers to carry independent prognostic information in patients with unstable coronary artery disease as well. ST-segment depression in the admission ECG is known to be an important indicator of poor outcome in these patients. The present study investigates the prognostic capacities of the ECG in combination with biochemical admission measurements in 516 patients admitted to hospital with unstable coronary artery disease. METHODS AND RESULTS: Baseline ECG recordings and blood samples were collected for central analysis. The patients were followed up for 30 days, and predefined end points, ie, death, myocardial infarction, and refractory angina, were registered as end points. By univariate analysis, ST-segment depression, inverted T waves in >/=5 leads, TnT >/=0.1 microg/L, TnI >/=0.5 microg/L, myoglobin >/=40 microg/L, female sex, and age >/=65 years were predictors of death and myocardial infarction at 30 days. By multivariate analysis, female sex, ST-segment depression at randomization, or inverted T-waves in >/=5 leads were the only independent predictors of death or myocardial infarction. On the basis of baseline ECG ST-T changes and CK-MB mass/TnT/TnI/myoglobin levels, the patients were divided into 3 subgroups at high (14% event rate), intermediate (6%), and low (3%) risk of early death/myocardial infarction. CONCLUSIONS: The present study found the combination of baseline values of TnT, TnI, CK-MB mass, and ST-T changes in the ECG to be effective for early risk stratification in patients with unstable coronary artery disease.

Cloning of sucrose:sucrose 1-fructosyltransferase from onion and synthesis of structurally defined fructan molecules from sucrose.

Sucrose (Suc):Suc 1-fructosyltransferase (1-SST) is the key enzyme in plant fructan biosynthesis, since it catalyzes de novo fructan synthesis from Suc. We have cloned 1-SST from onion (Allium cepa) by screening a cDNA library using acid invertase from tulip (Tulipa gesneriana) as a probe. Expression assays in tobacco (Nicotiana plumbaginifolia) protoplasts showed the formation of 1-kestose from Suc. In addition, an onion acid invertase clone was isolated from the same cDNA library. Protein extracts of tobacco protoplasts transformed with this clone showed extensive Suc-hydrolyzing activity. Conditions that induced fructan accumulation in onion leaves also induced 1-SST mRNA accumulation, whereas the acid invertase mRNA level decreased. Structurally different fructan molecules could be produced from Suc by a combined incubation of protein extract of protoplasts transformed with 1-SST and protein extract of protoplasts transformed with either the onion fructan:fructan 6G-fructosyltransferase or the barley Suc:fructan 6-fructosyltransferase.

Clinical application of two novel rapid bedside tests for the detection of cardiac troponin T and creatine kinase-MB mass/myoglobin in whole blood in acute myocardial infarction.

The objective of this study was to determine whether two novel rapid bedside assays for whole-blood detection of cardiac troponin T and creatine kinase (CK)-MB mass/myoglobin could rule out or rule in acute myocardial infarction in patients with acute chest pain. Ninety-two patients with chest pain <12 h prior to admission were investigated. No difference in the cumulative sensitivity of the TropT test and the CARDIAC STATus test (CK-MB mass and myoglobin in combination) was found 6 h after admission (94 vs. 97%). The cumulative positive predictive value of the TropT test and CARDIAC STATus test 6 h after admission was 97 and 76%, respectively. The negative predictive value was 97% for the TropT test and 98% for the CARDIAC STATus test at this time point. Our data show that the rapid assays provide diagnostic as well as prognostic information shortly after admission.

Anti-HLA alloantibody is found in children but does not correlate with a lack of HIV type 1 transmission from infected mothers.

Searching for mechanisms of natural resistance to HIV infection with which to guide HIV vaccine design, we have examined antibody responses to HLA class I antigens in children of HIV-1-infected mothers. Anti-HLA antibodies are known to block HIV infectivity in vitro and can be protective against SIV challenge in macaques immunized with purified class I HLA. It was hypothesized that alloantibody to maternal HLA in children might contribute to the prevention of mother-to-child transmission of HIV-1. In fact, a surprisingly high proportion of the children examined, 22%, were found to have antibody against class I alloantigens. This alloantibody, however, did not correlate with the HIV status of the children and was found in a similar proportion of children of HIV-negative mothers. The HLA specificity of the antibody was not correlated with noninherited maternal HLA alleles and occurred with a higher frequency in older children. This result suggests environmental factors, rather than exposure to maternal cells, are involved in the formation of the alloantibody. The finding that anti-allo-class I HLA antibodies are not associated with a decreased risk of mother-to-child transmission indicates that this humoral immune response is unlikely to be the natural mechanism that accounts for the lack of transmission observed in many births. This result, however, does not preclude the further investigation of cellular alloimmune responses, or the use of alloimmunization as an artificial HIV immunization strategy.

Naturally occurring IgG anti-HLA alloantibody does not correlate with HIV type 1 resistance in Nairobi prostitutes.

In an effort to identify an immunological basis for natural resistance to HIV-1 infection, we have examined serum antibody responses to HLA class I antigens in female prostitutes of the Nairobi Sex Workers Study. Anti-HLA antibodies are known to block HIV infectivity in vitro and can be protective against SIV challenge in macaques immunized with purified class I HLA. Thus, it was postulated that broadly cross-reactive alloantibodies recognizing common HLA alleles in the client population might contribute to the prevention of heterosexual transmission of HIV. In fact, 12% of the women were found to have serum IgG antibodies against class I alloantigens. However, this alloantibody did not correlate with the HIV status of the women and was found in a similar proportion of HIV-positive and HIV-resistant women. The observed levels of alloantibody did not increase with HIV infection in susceptible individuals, suggesting that potential antigenic mimicry between HIV and host HLA class I antigens does not significantly increase levels of anti-class I antibodies. The lack of correlation between serum anti-allo-class I HLA antibodies and the risk of sexual transmission indicates that this humoral immune response is unlikely to be the natural mechanism behind the HIV-resistance phenotype of persistently HIV-seronegative women. This result, however, does not preclude the further investigation of alloimmunization as an artificial HIV immunization strategy.