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PubMed1998

A model for the prediction of time to union in fractures of the tibia.

BACKGROUND AND PURPOSE: This report covers the second arm of a trial, the main focus of which was to assess the effect of interferential currents (IFCs) on time to union in tibial fractures. No significant improvement was found with the use of IFCs for the parameters employed (Fourie & Bowerbank, 1997). METHODS: The focus of this study is the development of logistic regression models which used subject characteristics to predict non-union of fracture within 24, 32 and 40 weeks. Such models could be used to identify clients for consideration of alternative interventions, for example, electric current stimulation, bone grafting or the injection of bone morphogenic proteins (BMPs). The usefulness of such models would depend on their ability to correctly identify subjects whose fractures do or do not unite. These models were validated with respect to their sensitivity and specificity to predict non-union for a separate data set. RESULTS: The results indicated, for instance, that use of a model to predict non-union of fracture within 24 weeks would lead to 27% of subjects being correctly classified (as union or non-union), 51% of subjects whose fractures did not unite within 24 weeks were identified and 65% of subjects (diagnosed as non-union) whose fractures did not unite within 24 weeks (the closer these values are to 100% the more accurate the model). CONCLUSIONS: The conclusion reached was that the models may have value for low-cost, non-invasive interventions, but that they could not be used to predict those cases where surgical involvement would be necessary, due to the high false-positive rate.

Adult↗
PubMed1996

Using a coronary risk score for screening and intervention in general practice. British Family Heart Study.

AIM: To investigate whether a risk score proposed by the British Regional Heart Study (BRHS), derived from data collected in 1978-1980, provides an appropriate basis for current coronary risk factor screening and intervention in general practice. METHODS: The BRHS risk score was applied to 1993 men aged 40-59 years and 1353 women aged 35-59 years, from 13 general practices in England, Wales and Scotland, who had health checks during 1991-1992 in the British Family Heart Study (FHS). Modifications to the BRHS risk score were made in order to identify subjects with a current high risk compared with others of the same age and sex. These were validated on 3272 men and 2229 women recruited from different general practices during 1992-1994 in the FHS. RESULTS: Only 9% of men in the FHS fell into the published top (highest risk) quintile of the BRHS score, versus an expected 20%, and 44% fell into the bottom quintile. Scores were, on average, substantially lower in the FHS men than in the BRHS men, principally because of lower measured cholesterol levels (using a Reflotron) and a lower prevalence of cigarette-smoking. The BRHS scores also tended to increase with age, disproportionately identifying older subjects, and were substantially lower in women than in men. Simple age-related modifications to the risk score were therefore devised to overcome these problems. These modifications performed well in the validation. CONCLUSIONS: The substantial difference in risk scores between the BRHS and FHS men may reflect both a real reduction in risk and changes in calibration and methodology. Current use of the BRHS risk score may therefore mislead doctors and patients in the direction of complacency. In addition, the published BRHS risk score has an age-dependence that is undesirable in terms of guiding the intensity of lifestyle intervention which should be offered to an individual patient. The simple modifications proposed provide a more appropriate basis for coronary risk factor screening and intervention in general practice, and one that can be used both for men and for women.

Adult↗
PubMed2000

The nucleotide sequence of two new DP alleles, DPA1*02015 and DPB1*8401, identified in a Chinese subject.

The HLA-DP genes (HLA-DPA1 and -DPB1) are encoded by the major histocompatibility complex (MHC) on human chromosome 6. They are involved in the presentation of antigen to CD4+ T cells as part of the class II antigen-presentation pathway. During a small study of Oriental subjects (11 Chinese and 26 Japanese subjects), one Chinese subject was identified as having numerous heterozygous sites within the second exon of both DPA1 and DPB1. These were further analysed using novel codon-specific primers. Sequencing analysis using these primers determined the subject to have DPA1*0103/*02015 and DPB1*0501/*8401; these new alleles have been submitted to GenBank and assigned the accession numbers AF098794 and AF077015, respectively.

Alleles↗
PubMed2006

Time to abandon microalbuminuria?

The term microalbuminuria--a urinary albumin excretion (UAE) between 20 and 200 microg/min--has been introduced to identify subjects at increased risk of renal and cardiovascular disease. However, the relationship between albuminuria and risk is not restricted to the microalbuminuric range and extends to as low as 2-5 microg/min. On the contrary, the increase of UAE above 200 microg/min (macroalbuminuria) heralds the onset of proteinuria (urinary protein excretion above 0.5 g/24 h) and progressive renal and cardiovascular disease. Albuminuria is a component of the metabolic syndrome and may represent a marker of the increased risk of renal and cardiovascular disease associated with insulin resistance and endothelial dysfunction. Proteinuria is a sign of established kidney damage and plays a direct pathogenic role in the progression of renal and cardiovascular disease. Albuminuria reflects functional and potentially reversible abnormalities initiated by glomerular hyperfiltration, proteinuria, a size-selective dysfunction of the glomerular barrier normally associated with glomerular filtration rate (GFR) decline that may result in end-stage renal disease. Thus, the limit of 200 microg/min segregates patients with albuminuria or proteinuria who are at quite different risk. Among subjects with albuminuria, however, there is a continuous relationship between albumin excretion and risk and no lower bound between normal albuminuria and microalbuminuria can be identified that segregates subjects at different risk. Thus, the terms microalbuminuria and macroalbuminuria could be replaced by the concepts of albuminuria- and proteinuria-associated diseases. Future studies are needed to identify levels of albuminuria below which therapy is no longer beneficial.

Albuminuria↗
PubMed1991

Combined use of alcohol and nicotine gum.

This study evaluated the effects of chewing nicotine gum immediately before and just after drinking a moderate amount of alcohol. Four research questions were addressed. First, does chewing nicotine gum prior to drinking alcohol attenuate the increased craving to smoke that is typically associated with alcohol use? Second, does drinking prior to chewing reduce the gum's effectiveness? Third, are significant side effects observed with nicotine gum, and is their severity affected by alcohol use? Finally, can we identify subjects who are more likely to respond well to the gum on the basis of smoking history or pattern or other descriptive-demographic, psychologic, or historical variables? Smokers who had abstained for at least 12 h were studied in a fully crossrandomized experimental design that contrasted nicotine gum (before or after drinking) versus sugarless gum, and alcohol versus a no-alcohol comparison condition. Nicotine gum use was associated with significantly greater immediate reduction in craving to smoke, regardless of whether it preceded or followed alcohol, but the effects were weak and short-lived in either case. Moderate use of alcohol after chewing the gum eliminated virtually all of its beneficial effects. Mild side effects were common with nicotine gum, but equally so regardless of alcohol use. A small battery of demographic and historical variables failed to identify those subjects who responded well to nicotine gum.

Adult↗
PubMed2000

Cost effectiveness analysis of BMD referral for DXA using ultrasound as a selective pre-screen in a group of women with low trauma Colles' fractures.

Measurements of bone density (BMD) are central to the World Health Organisation (WHO) approach to the definition of osteoporosis. Dual energy X- ray absorptiometry (DXA) remains the gold standard technique for measuring the bone mineral density (BMD) but Quantitative Ultrasound (QUS) is an attractive alternative method of bone assessment because it is easy to use and relatively inexpensive. It has been suggested that QUS could be used as a selective population pre-screen, to maximise the cost effectiveness of referral for DXA assessment of BMD. We set out to examine how such an approach might perform in the assessment of women with low trauma Colles' fracture. In 46 women aged 50-80 (mean 67) years we used DXA to measure BMD at lumbar spine and hip, and heel bone ultrasound to measure Broad Band Attenuation (BUA) and Velocity of Sound (VOS). We calculated local costs of pounds sterling 45 for DXA and pounds sterling 15 for QUS. We identified a BUA threshold of 60 dB/MHz as most cost effective as pre-screen, and calculated a sensitivity of 93% and specificity of 84% in identifying those subjects who were subsequently identified as having osteoporosis by DXA. DXA assessment of all patients had a cost of pounds sterling 77 per osteoporotic subject identified. We examined the cost-effectiveness of using QUS as a pre-screen, only referring subjects for more expensive DXA assessment if BUA was less than 60 dB/MHz. However this approach had no advantage, still costing pounds sterling 78 per osteoporotic subject identified. QUS assessment does not appear cost-effective as a pre-screen for DXA, even in this high risk group of women with low trauma Colles' fracture. A QUS pre-screen would only be cost-effective if the scan could be performed at a substantially lower cost.

Absorptiometry, Photon↗
PubMed2000

Characteristic subjective experiences of schizophrenia.

The purpose of the study was to identify subjective experiences that are characteristic of schizophrenia. A questionnaire for self-assessment of disturbances in several cognitive-perceptual areas (the Eppendorf Schizophrenia Inventory) was constructed and administered to first episode schizophrenia patients (SCHf; n = 45), negative-syndrome schizophrenia patients (SCHn; n = 45), remitted schizophrenia subjects (SCHr; n = 24), depressive patients (DEP; n = 43), alcoholic patients (ALC; n = 48), obsessive-compulsive patients (OCD; n = 46), and healthy controls (CON; n = 57). Comparisons between the SCHf, SCHn, DEP, ALC, and OCD groups and a subsequent factor analysis revealed four schizophrenia-specific dimensions: Attention and Speech Impairment (AS), Ideas of Reference (IR), Auditory Uncertainty (AU), and Deviant Perception (DP). Further analyses suggested that the AS syndrome represents a mediating vulnerability factor, while IR, AU, and DP probably are reversible episode indicators. The results may contribute to the refinement of the measurement of specific prepsychotic signs, thus facilitating the development of early intervention approaches.

Adult↗
PubMed1992

Triazolam as a discriminative stimulus in humans.

Seven healthy normal male and female volunteers (19-42 years) were trained to discriminate between the benzodiazepine triazolam (0.32 mg/70 kg; e.g. drug A) and placebo (e.g. drug B). During the first four daily sessions, drug A and drug B were administered orally in capsules 60 min prior to the session on alternate days and subjects were informed of the drug label at the time of drug administration. Subsequently, drug A and drug B were administered in a randomized-block fashion and subjects identified the drug code they thought they received. Subjects were informed of the drug code post-session. Once the criterion for discrimination was met (i.e. correct drug code identification on four consecutive sessions), the dose-effect curve for triazolam (0.1-0.75 mg/70 kg) was determined. The discrimination was acquired in all subjects; triazolam (0.32 mg/70 kg) and placebo produced approximately 85-95% correct responding. During the dose-effect curve determination, triazolam produced dose-related increases in triazolam-appropriate responding and self-reported sedation and drug strength. These results indicate that a triazolam-placebo discrimination can be acquired and that the triazolam discriminative stimulus effect is related to dose and to self-reported sedation.

Adult↗
PubMed2006

Highly active antiretroviral therapy interruption: predictors and virological and immunologic consequences.

OBJECTIVE: To characterize the magnitude and the predictors of highly active antiretroviral therapy (HAART) interruption (TI) and to investigate its immunologic and virological consequences. METHODS: Using Concerted Action on Seroconversion to AIDS and Death in Europe data from 8,300 persons with well-documented seroconversion dates, we identified subjects with stable first HAART (for at least 90 days) not initiated during primary infection. A TI was defined as an interruption of all antiretroviral therapy drugs for at least 14 days. RESULTS: Of 1,551 subjects starting HAART, 299 (19.3%) interrupted treatment. Median (interquartile range) duration of the TI was 189 (101-382) days. The cumulative probability (95% confidence interval) of TI at 2 years was 15.9% (14.0%-18.1%). Women were more likely to have a TI than men in the same exposure group (35.8% vs 24.2% among drug users, 22.1% vs 13.3% among heterosexuals; P < 0.05). Higher baseline viremia and poor immunologic response to HAART were associated with higher probabilities of TI. Median (interquartile range) individual CD4 cell loss during TI was 94 (1-220) cells/microL. Older age at HAART (>40 yr), lower pre-HAART nadir (<200 cells/microL), and lower CD4 at start of TI (<350 cells/microL) were significantly associated with greater relative CD4 loss during TI. CONCLUSIONS: We estimate that almost 1 in 6 subjects on HAART interrupts treatment by 2 years. Further research is needed to investigate the reasons why TI is higher in women. We have identified characteristics of subjects with the greatest risk for CD4 loss in whom TI may have greater risks.

Adult↗
PubMed2004

Mutation analysis of the BOULE gene in men with non-obstructive azoospermia: identification of a novel polymorphic variant in the black population.

The BOULE gene is a member of the 'deleted in azoospermia'DAZ family. As in flies and worms, disruption of the BOULE homologues leads to meiotic defects during the first meiotic division, we screened the coding region of the BOULE gene from 40 infertile men with non-obstructive azoospermia or severe oligoasthenoteratozoospermia by denaturing high-pressure liquid chromatography and direct sequencing in order to make progress in elucidating the aetiology of male infertility. Two infertile patients were heterozygous for a novel G to C transversion in exon 2 resulting in a Q2E amino acid substitution. As these two infertile men were from African origin, screening of fertile African subjects identified this novel variant in two fertile male subjects suggesting that this novel Q2E substitution had non-pathologic role. Taking into account the size of our sample, we conclude that BOULE coding sequence mutations are not an important factor in the aetiology of azoospermia.

Amino Acid Sequence↗
PubMed2002

Dehydroepiandrosterone, 17alpha-hydroxyprogesterone and aldosterone responses to the low-dose (1 micro g) ACTH test in subjects with preclinical adrenal autoimmunity.

OBJECTIVE: The appearance of 21-hydroxylase autoantibodies (21OHAbs) identifies subjects with preclinical adrenal insufficiency. In 21OHAb-positive subjects, the adrenocortical function is best evaluated by peak cortisol (F) levels after the low-dose (1 micro g) ACTH stimulation test (LDT). No information is currently available on the correlation between F and other adrenocortical hormone responses to the LDT in subjects with an ongoing autoimmune adrenal process. In this study, we tested the hypothesis that the dehydroepiandrosterone (DHEA), 17alpha-hydroxyprogesterone (17OHP) and aldosterone (A) responses to the LDT are consensual to that of F during the preclinical phase of autoimmune adrenal insufficiency. DESIGN AND PATIENTS: We studied 12 subjects positive for 21OHAb, in the absence of clinical signs of adrenal insufficiency. On the basis of peak F levels after the LDT, and according to the lower level of normal observed in 15 healthy volunteers (510.4 nmol/l), patients were subdivided into two groups: group A, n = 6 subjects with normal F response; and group B, n = 6 subjects with impaired F response. Results were expressed as absolute delta increase (Delta) between peak and basal levels. RESULTS: DeltaF was significantly higher in group A (314.5 +/- 115.8 nmol/l) than in group B (151.7 +/- 88.2 nmol/l) (P = 0.041). DeltaDHEA and Delta17OHP were also significantly higher in group A (17.0 +/- 13.5 nmol/l and 6.1 +/- 4.4 nmol/l, respectively) than in group B (0.69 +/- 2.25 nmol/l and 1.9 +/- 1.7 nmol/l, respectively) (P = 0.002 and P = 0.041). The difference in DeltaA between the two groups did not reach statistical significance (group A 321.8 +/- 272.0 pmol/l vs. group B 157.0 +/- 154.0 pmol/l). DeltaDHEA, Delta17OHP and DeltaA tended to correlate positively with DeltaF (P = 0.039, P = 0.039 and P = 0.044, respectively), but the correlations did not reach significance after correction of the P-value. CONCLUSIONS: Our study demonstrates a high concordance between F and DHEA, 17OHP and A responses to the LDT in subjects with preclinical adrenal autoimmunity, thus strengthening the concept that the LDT is an accurate test to identify early adrenal dysfunction.

17-alpha-Hydroxyprogesterone↗
PubMed1991

A combined single-blind, double-blind, placebo-controlled study to determine the reproducibility of hypersensitivity reactions to aspartame.

Aspartame is an O-methyl ester composed of phenylalanine and aspartic acid. After its final approval as a sweetener in 1981, a number of reports of adverse reactions to aspartame appeared in the literature. To explore the pathogenesis of such reactions, we initiated a study in July 1986 to identify subjects with hypersensitivity reactions to aspartame with blinded challenge procedures. The study was closed after 32 months. During that time, we advertised in local newspapers and worked closely with the local community of allergists and dermatologists in an attempt to recruit subjects with hypersensitivity reactions to aspartame. A total of 61 self-referrals and physician referrals were screened, with 20 referrals evaluated in clinic. After this evaluation, 12 patients underwent single- and double-blind challenge with up to 2000 mg of aspartame. No subject with a clearly reproducible adverse reaction to aspartame was identified. In summary, we found that it is difficult to recruit study subjects with a history of hypersensitivity reactions to aspartame and that subjects who believed themselves allergic to aspartame did not have reproducible reactions.

Adult↗
PubMed2005

Progression of mild cognitive impairment to Alzheimer's or vascular dementia versus normative aging among elderly Chinese.

To compare differences in evolutionary progressions from Mild Cognitive Impairment (MCI) to dementia of Alzheimer's type (DAT) or to vascular dementia (VaD) versus normal aging, subjects identified as MCI or as cognitively normal (CN) during standard cognitive evaluations among a large epidemiological study designed to determine prevalence and incidence of dementia and its major subtypes in Beijing, China were re-examined after an interval of approximately 3 years, repeating the same investigation protocol as at baseline. MCI subjects meeting criteria for dementia and the two major subtypes, DAT and VaD were identified at follow-up evaluation. Annual conversion rates for combined dementias and for major subtypes of DAT and VaD, from MCI, were compared with conversion rates among CN subjects. Relative risks for conversion from MCI to major subtypes of dementia were also compared with CN subjects by Cox regression models. 175 MCI and 400 CN subjects were identified at baseline. Among 121 MCI subjects available at follow-up, 51 were diagnosed with dementia (29 with DAT, 18 with VaD and 4 with other dementias), compared with 14(10 DAT, 3 VaD and 1 other type dementia) diagnosed as dementia among 281 CN subjects available at follow-up. Annual conversion rates calculated from MCI to all dementias, compared with conversion rates from CNs, were 14.1% versus 1.6%. Specifically for DAT, annual conversion rates were 8.0% versus 1.1% and for VaD were 5.0% versus 0.3%. Relative risks for developing all dementias, DAT and VaD among MCI subjects were 9, 6 and 5 times greater than among CN subjects. Conversion rates among MCI subjects to dementia, and major subtypes, for elderly Chinese residents of Beijing were comparable with results reported among similar studies worldwide. Risks of developing dementia, and major subtypes, among MCI subjects in Beijing were significantly higher than among normal subjects. Identification of MCI among elderly populations provides the possibilities for dementia prevention and treatment within prodromal stages.

Age Distribution↗
PubMed2002

A comparison of MRI and laparoscopy in detecting pelvic structures in cases of vaginal agenesis.

OBJECTIVE: To determine whether laparoscopy improves detection of uterine structures over MRI in cases of vaginal agenesis. DESIGN: Prospective case series. SETTING: Ambulatory pediatric gynecology clinic in a tertiary care children's hospital. PARTICIPANTS: Subjects with vaginal agenesis who had an MRI to detect uterine structures. MAIN OUTCOME MEASURES: A chart review identified subjects with vaginal agenesis who had an MRI to assess müllerian structures. The MRI findings were correlated with physical exam, presenting symptoms, and operative findings. We assessed degree of agreement between laparoscopy and MRI in patients both with and without pelvic pain to determine sensitivity and specificity of MRI in predicting uterine structures confirmed on laparoscopy. RESULTS: Twenty-two subjects with vaginal agenesis were identified and 14 had both an MRI and laparoscopic evaluation. MRI successfully predicted uterine anomalies in six cases (43%) and lack of uterine structures in one case (8%). MRI diagnosis did not correlate with laparoscopic findings in the remaining seven cases (50%). Among subjects presenting with no complaints of pelvic pain (n = 6), three had negative MR imaging but positive laparoscopy. Using laparoscopy as a gold standard, MRI had a sensitivity of 53% for accurately detecting uterine anomalies confirmed on laparoscopy. CONCLUSION: Laparoscopy improves detection of uterine structures over MRI alone in women with vaginal agenesis.

Adolescent↗
PubMed1985

Comparison of the lay Diagnostic Interview Schedule and a standardized psychiatric diagnosis. Experience in eastern Baltimore.

We studied DSM-III diagnoses made by the lay Diagnostic Interview Schedule (DIS) method in relation to a standardized DSM-III diagnosis by psychiatrists in the two-stage Baltimore Epidemiologic Catchment Area mental morbidity survey. Generally, prevalence estimates based on the DIS one-month diagnoses were significantly different from those based on the psychiatric diagnoses. Subjects identified as cases by each method were often different subjects. Measured in terms of kappa, the chance-corrected degree of agreement between the DIS and psychiatrists' one-month diagnoses was moderate for DSM-III alcohol-use disorder (abuse and dependence combined), and lower for other mental disorder categories. The unreliability of either the DIS or psychiatric diagnoses is one potential explanation for the observed disagreements. Others include the following: insufficient or inadequate information (on which to base a diagnosis); recency of disorder; incomplete criterion coverage; overinclusive DIS questions; and degree of reliance on subject symptom reports. Further study of the nature and sources of these discrepancies is underway. This work should produce a more complete understanding of obstacles to mental disorder case ascertainment by lay interview and clinical examination methods in the context of a field survey.

Adolescent↗
PubMed1993

To drink or not to drink? Assessing conflicting desires in dependent drinkers in treatment.

Reactivity to Alcohol and Neutral Cues was compared in male, inpatient problem drinkers (N = 30). Subjects reported an overall desire not to drink alcohol which decreased in the presence of the Alcohol Cue. There were no cue-specific changes in heart rate, blood pressure and arousal level and a non-significant trend for increased stress in the Alcohol Cue condition. Subgroups of subjects reporting positive and negative desire for alcohol were identified. Subjects who reported negative desire for alcohol in the Alcohol Cue condition also reported greater self-efficacy to resist drinking in the future. These findings have implications for understanding the nature of self-reported desire for alcohol and its potential role in the treatment of alcohol dependence.

Adult↗
PubMed1982

Alpha 1-antitrypsin deficiency: the radiological features of pulmonary emphysema in subjects of Pi type Z and Pi type SZ: a survey by the British Thoracic Association.

In a multicentred survey of alpha 1-antitrypsin deficiency, radiological details have been obtained in 165 subjects homozygous for Pi type Z and in 23 subjects heterozygous for type SZ. Eight-five per cent of all type Z subjects had radiological evidence of pulmonary emphysema which was commoner in smokers than in those who had never smoked and which predominantly affected the lower zones of the lungs; 66% of the type Z subjects identified through family studies also had emphysema. Emphysema in subjects of Pi type SZ was limited to those who had smoked; this phenotype may not carry a specific risk of emphysema.

Adult↗
PubMed2001

Association of specific HLA phenotypes with left ventricular mass and carotid intima-media thickness in hypertensives.

The aim of this study was to investigate the hypothesis that the expression of certain HLA antigens may constitute a risk marker for cardiovascular hypertrophy in subjects with arterial hypertension. We examined 158 subjects with newly diagnosed arterial hypertension. HLA class I (-A, -B, -Cw) and class II (-DR, -DQ) antigens were studied by two-step microlymphocytotoxic technique in peripheral T and B lymphocytes. Carotid intima-media thickness (IMT) was determined noninvasively by ultrasonography. The left ventricular mass was calculated according to the formula of Devereux and was normalized by the individual's height (LVM/h). The individuals with DR13 and DR17 were characterized by higher values of IMT compared to those without these HLA (0.096+/-0.018 cm v 0.085+/-0.021 cm, P = .011, 0.100+/-0.019 cm v 0.084+/-0.021 cm, P = .012, respectively). The presence of HLA DQ7 was characterized by markedly higher values of IMT that just failed to reach statistical significance (0.091+/-0.019 cm v 0.084+/-0.022 cm, P = .045). Furthermore, subjects with HLA DQ7 and DR11 exhibited higher values of LVM/h in comparison to those without these HLA (191.3+/-36.2 g/m v 166.9+/-41.0 g/m, P = .029 and 194.6+/-34.3 g/m v 166.6+/-40.9 g/m, P = .034, respectively). Hypertensive subjects with HLA B51 tended to have lower LVM/h (166.6+/-39.0 g/m with v 176.0+/-41.7 g/m without HLA B51, P = .045). In conclusion, it can be postulated that certain HLA phenotypes exhibit an association with increased carotid IMT and left ventricular mass in hypertensive subjects. The determination of these antigens may help to identify subjects at high risk for cardiovascular events.

Adult↗