Is benign paroxysmal positional vertigo underdiagnosed in hospitalised patients?

OBJECTIVES: To investigate the proportion of sufferers of benign paroxysmal positional vertigo among hospitalised patients in Hong Kong who complained of dizziness, and to determine the predictive values and likelihood ratios of classical presenting symptoms. DESIGN: Cross-sectional study. SETTING: Convalescence/rehabilitation hospital, Hong Kong. PATIENTS: A cohort of 88 newly admitted patients, who complained of dizziness or complained of having had dizziness in the 2 weeks prior to admission from September 2005 to February 2006. MAIN OUTCOME MEASURES: Presence of the pathognomonic nystagmus of benign paroxysmal positional vertigo. RESULTS: Five patients had benign paroxysmal positional vertigo, all with the posterior type. The frequency of its occurrence among patients complaining of dizziness was 6% (95% confidence interval, 1-11%), which was more than double the figure of 3% in our local convalescence/rehabilitation hospitals, though this difference was not statistically significant. Regarding the five identified patients, in two it involved the left ear, in two others the right ear, and in one it was bilateral. All four classical presenting symptoms had low positive predictive values, high negative predictive values, and small likelihood ratios. CONCLUSION: Benign paroxysmal positional vertigo in the setting of a convalescence/rehabilitation hospital in Hong Kong seems to be underdiagnosed. Small and insignificant likelihood ratios for the classical presenting symptoms preclude their use in making the diagnosis. However, absence of these symptoms in a clinical setting of low occurrence rate can be regarded as against the diagnosis.

A stochastic-advective transport model for NAPL dissolution and degradation in non-uniform flows in porous media.

Remediation schemes for contaminated sites are often evaluated to assess their potential for source zone reduction of mass, or treatment of the contaminant between the source and a control plane (CP) to achieve regulatory limits. In this study, we utilize a stochastic stream tube model to explain the behavior of breakthrough curves (BTCs) across a CP. At the local scale, mass dissolution at the source is combined with an advection model with first-order decay for the dissolved plume. Field-scale averaging is then employed to account for spatial variation in mass within the source zone, and variation in the velocity field. Under the assumption of instantaneous mass transfer from the source to the moving liquid, semi-analytical expressions for the BTC and temporal moments are developed, followed by derivation of expressions for effective velocity, dispersion, and degradation coefficients using the method of moments. It is found that degradation strongly influences the behavior of moments and the effective parameters. While increased heterogeneity in the velocity field results in increased dispersion, degradation causes the center of mass of the plume to shift to earlier times, and reduces the dispersion of the BTC by lowering the concentrations in the tail. Modified definitions of effective parameters are presented for degrading solutes to account for the normalization constant (zeroth moment) that keeps changing with time or distance to the CP. It is shown that anomalous dispersion can result for high degradation rates combined with wide variation in velocity fluctuations. Implications of model results on estimating cleanup times and fulfillment of regulatory limits are discussed. Relating mass removal at the source to flux reductions past a control plane is confounded by many factors. Increased heterogeneity in velocity fields causes mass fluxes past a control plane to persist, however, aggressive remediation between the source and CP can reduce these fluxes.

Protein carbonyl measurements show evidence of early oxidative stress in critically ill patients.

OBJECTIVE: To determine whether there is evidence of oxidative injury in patients who are critically ill with severe sepsis or major trauma, by measuring protein and lipid oxidation products. DESIGN: A prospective, observational study. SETTING: Critical care unit at a university teaching hospital. PATIENTS: Twenty-two patients with severe sepsis (Acute Physiology and Chronic Health Evaluation II score 15-34) and eight patients with major trauma (Injury Severity Score 26-50). INTERVENTIONS: Plasma and bronchoalveolar lavage fluid was collected regularly during the first 10 days after trauma or onset of sepsis. Both fluids were analyzed for protein carbonyl concentrations as a measure of protein oxidation and thiobarbituric acid-reactive substances as a measure of lipid peroxidation. Myeloperoxidase concentrations were measured as an index of neutrophil activation. MEASUREMENTS AND MAIN RESULTS: Protein carbonyl concentrations were initially highly elevated compared with those in healthy adults in the plasma of both patient groups. They fell significantly within the first few days but remained above control values. Protein carbonyl concentrations were also high initially in bronchoalveolar lavage fluid and fell significantly with time. Thiobarbituric acid-reactive substances were not increased in plasma, and varied over a wide concentration range in lavage fluid. Myeloperoxidase activity reached micromolar levels in the lavage fluid when corrected for dilution, and was significantly higher in the plasma of the sepsis patients who subsequently died. There was a strong correlation between carbonyl concentrations in lavage fluid and plasma, and between protein carbonyls, thiobarbituric acid-reactive substances and myeloperoxidase in the lungs. CONCLUSIONS: Our results provide evidence of oxidation occurring early in severe sepsis and major trauma patients, with protein carbonyl measurements providing a sensitive index of this process. High protein carbonyl concentrations in plasma as well as bronchial aspirates indicate that oxidation is not restricted to the lungs. The correlation between oxidative measures and myeloperoxidase concentrations in the lung indicates that neutrophil oxidants could be responsible for the injury.

TLCQA: quantitative study of thin-layer chromatography.

UNLABELLED: An accurate, simple and low-cost image-analysis system has been set up for capturing thin-layer chromatography images, and a software package, TLCQA, has also been developed for both qualitative and quantitative analyses using the acquired image. AVAILABILITY: Available upon request from the authors. CONTACT: bcftchau@poly.edu.hk

Treatment of dystonia with botulinum A toxin: a retrospective study of 170 patients.

OBJECTIVE: Botulinum A toxin has been reported to provide excellent symptomatic relief for patients with dystonia. To analyse the treatment, complications, and outcome of patients receiving botulinum A toxin injection, the case records of 170 patients attending the Botox Clinic at the Kwong Wah Hospital from 1 December 1992 to 31 December 1996 were reviewed. Of these 170 patients, 130 (76.5%) had idiopathic hemifacial spasm, 18 (10.6%) had blepharospasm, 18 (10.6%) had spasmodic torticollis, and 4 (2.4%) had generalised or focal limb dystonia. One hundred and sixty-six (97.6%) patients were Chinese. The average dose of botulinum A toxin required for an optimal response was 14.54 U for those with hemifacial spasm, 49.64 U for those blepharospasm, and 137 U for those with spasmodic torticollis. Among patients with hemifacial spasm, 103 (81.7%) gave a good response, 21 (16.7%) gave a partial response, and there was no response in two (1.6%) patients. The corresponding figures for patients with blepharospasm were 7 (38.9%), 10 (55.6%), and 1 (5.6%), respectively, and for those with spasmodic torticollis, the figure were 6 (37.5%), 6 (37.5%), and 4 (2.5%), respectively. Complications from botulinum A toxin injection were rare (less than 10%), minor, transient, and usually dose-related. In conclusion, idiopathic hemifacial spasm was the most common type of movement disorder encountered in our Botox Clinic and botulinum A toxin injection was safe and effective in the majority of patients.

Protein carbonyl measurement by a sensitive ELISA method.

We describe a new immunoassay for measuring protein carbonyls as an index of oxidative injury. Protein samples were reacted with dinitrophenylhydrazine then adsorbed to wells of an ELISA plate before probing with a commercial antibody raised against protein-conjugated dinitrophenylhydrazine. The biotin-conjugated primary antibody was then reacted with streptavidin-biotinylated horseradish peroxidase for quantification. The method was calibrated using oxidized albumin and results correlated well with the colorimetric carbonyl assay. The method required only 60 microg protein and was used to analyze the amount of protein carbonyls in plasma and lung aspirate samples. It was sensitive in the 0-2.5 nmol/mg protein range within which clinical samples fell and was linear up to 10 nmol/mg protein. The ELISA method for protein carbonyls is more sensitive and discriminatory than the colorimetric assay and should have wide application for analysing experimental and clinical samples, especially where concentrations are low and where only small amounts of sample are available.

Isolated hypoglossal nerve palsy in Behçet's disease.

Isolated hypoglossal nerve paresis as a manifestation of Behcet's disease has not been reported. We describe a 42-year-old man with isolated unilateral hypoglossal nerve paresis, who had had a five-year history of recurrent orogenital aphthae and relapsing arthritic manifestations. It is suggested that the nerve disorder represents a form of mononeuritis that may occur in Behcet's disease.

Molecular characterization of haemophilia A in southern Chinese.

41 unrelated southern Chinese haemophilia A patients were studied. The 5' promoter region, all 26 exons, their immediate 5' and 3' flanking splice junctions and the 3' untranslated region of the FVIII gene were amplified (including 16 different segments of exon 14) using GC-clamped primers. The GC-clamped PCR products were screened by denaturing gradient gel electrophoresis (DGGE) and fragments showing an abnormal migration pattern were sequenced. 17 mutations were identified, of which four were splicing defects, involving the first 1-6 nucleotide (nt) in the intervening sequences (IVS), six missense mutations, three nonsense mutations and four frameshift mutations. 14 other patients carried the type 1 inversion, affecting the distal copy of the FSA gene at the telomere of the X chromosome and the same gene in intron 22 of the FVIII gene. All the mothers studied (12/14) were carriers of the inversion. Two of these patients with inversion also have a co-existing missense mutation. In most cases the clinical severity of the disease corresponds to the genotype.

DNA analysis of Huntington's disease in southern Chinese.

Allelic frequencies of RFLPs at loci closely linked to the HD gene, D4S95, D4S91, D4S141, and D4S90, were determined in 13 Huntington's disease (HD) patients from nine Chinese families and 129 normal subjects. These were similar for non-HD and HD chromosomes and the HD gene in Chinese is associated with multiple haplotypes. Hence the HD gene probably arose independently in the background haplotypes of the Chinese population. The heterozygosity rates for the two most useful RFLP sites are 0.659 for D4S95-AccI VNTR and 0.494 for D4S141-HindIII. (CAG)n repeat numbers ranged from 12 to 27 in 174 normal chromosomes. In 52 meiotic recombinations, the (CAG)n repeats were stably inherited in normal families. In HD families, 12 of 13 HD patients had expanded (CAG)n repeats of 40 to 58. Additionally, 10 asymptomatic family members had expanded (CAG)n repeats and the inheritance of the expanded repeat was unstable in these families.

False non-paternity in a family for prenatal diagnosis of beta-thalassaemia.

Initial screening for the common beta-thalassaemia mutations with allele-specific oligonucleotide probes in an at-risk family suggested non-paternity. Subsequent DNA fingerprinting of the members proved otherwise. The mother had a codon 41/42 frameshift mutation and the father's defect, determined by direct sequencing of PCR-amplified beta gene, was a codon 43 nonsense mutation. In the affected children, the close proximity of these two defects resulted in the absence of a hybridization signal to the normal probe in that region and a wrong assumption of homozygosity for the codon 41/42 mutation. The non-reactivity of the father's amplified DNA to the codon 41/42 thalassaemic probe accounted for the initial wrong conclusion of non-paternity. Since prior screening for beta-thalassaemia mutations is done in all prenatal diagnosis programmes and concomitant inheritance of these two defects is relatively common in the Chinese, this 'artefact' of false non-paternity is worth noting.

Molecular defects in haemophilia B: detection by direct restriction enzyme analysis.

The common restriction fragment length polymorphisms (RFLPs) associated with the FIX gene: 5' BamH I, Dde I, BamH I (2), Taq I and 3' Hha I were absent or of low incidence in Southern Chinese and are therefore not useful for linkage analysis. No deletion was detected amongst seven consecutive unrelated haemophilia B patients, but one had an insertion of a 15 kb Pvu II fragment containing exon d. Using an alternate strategy of polymerase chain reaction (PCR) amplification and direct sequencing, the molecular defect in the other six patients was defined. The four novel mutations characterized were: nucleotide (nt) 6410 G----C (Gly12----Ala); nt 31261 delta T (stop codon 31 bp downstream); nt 31260 C----G (Thr380----Ser) and nt 31122 C----A (Ala34----Asp). Two patients had the same mutation at nt 6365, G----A (Arg-4----Gln), identical to one previously described in other ethnic groups, suggesting that this is a hotspot for mutation. Each of the mutations was found to affect an enzyme recognition site and could thus be identified by direct visualization of abnormal restriction fragments in amplified genomic DNA. This allows rapid and accurate DNA diagnosis of haemophilia B in an ethnic group which otherwise shows little or no polymorphism for the common RFLP sites.

Multiple XbaI polymorphisms for carrier detection and prenatal diagnosis of haemophilia A.

Three XbaI restriction fragment length polymorphisms (RFLPs) can be detected using the factor VIII-intron 22 probe (p482.6) in a XbaI-KpnI double digest of genomic DNA. The XbaI (A) site had been reported by Wion et al (1986) to be in intron 22, while the two additional sites. XbaI (B) and XbaI (C), are shown here to be X-linked and close to the XbaI (A) site. The frequencies of heterozygosity for these three sites are 0.49, 0.18 and 0.30 respectively. In 75 females the observed heterozygosity rate for the XbaI (A) site is 0.41 and this increased to 0.57 with the two additional sites. Care should be exercised when interpreting the XbaI RFLPs, since the 1.4 kb XbaI/KpnI fragment and the 4.8 kb XbaI fragment are associated with both positive XbaI (A) and XbaI (B) sites. By the combined use of the multiple XbaI polymorphisms with the BclI site in intron 18, the carrier detection rate would increase to 67%. Four prenatal diagnoses had been performed using the multiple XbaI polymorphisms.

Restriction fragment length polymorphism in the interzeta hypervariable region for prenatal diagnosis of non-deletion alpha thalassemia.

A Bam HI restriction fragment length polymorphism in the interzeta hypervariable region (IZ HVR) of the zeta-alpha gene cluster was used for the prenatal diagnosis of a pregnancy at risk for Hb H hydrops fetalis. The parents had zeta-alpha thalassemia 1 and non-deletion alpha thalassemia, respectively, and a previous hydrops was missed using the conventional method of gene detection. In this prenatal diagnosis, linkage to IZ HVR was used to exclude non-deletion alpha thalassemia, and the numbers of zeta and alpha genes in the fetus were quantitated to predict the exact genotype. Confirmation was made by analysis of cord blood at delivery.