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PubMed1994

Improving diagnosis of Huntington's disease by analysis of an intragenic trinucleotide repeat expansion.

OBJECTIVE: To develop an accurate presymptomatic test for Huntington's disease. METHOD: An improved polymerase chain reaction method was used to investigate the pattern of expansions of a CAG repeat sequence located in the 5' region of a gene recently found to produce the protein called Huntingtin. We documented the range of trinucleotide repeat expansions in the responsible gene in 82 affected individuals compared with 80 control subjects from a Western Australian population. RESULTS: The number of expanded repeats ranged from 40 to 73 in affected individuals and from 13 to 38 in normal controls. CONCLUSIONS: Polymerase chain reaction analysis of a CAG repeat sequence in the Huntington's disease gene clearly differentiated between normal and mutated alleles, providing an accurate diagnostic test for the disorder in individuals at risk. This predictive test has met with greater acceptance and demand than methods using family based linkage studies.

Base Sequence↗
PubMed1987

Prognostic value of consecutive peripheral pressure registration after reconstructive peripheral arterial surgery.

A reliable predictive test as a guide in selection for arterial reconstruction vs. primary amputation would be of great value. An ideal test should also be simple and noninvasive. We evaluated prediction based on preoperative and early postoperative (repeatedly in the first week) measurements of ankle and toe pressure in relation to patency 6 months after reconstructive peripheral vascular surgery in 39 patients. Occlusion occurred within 6 months in ten patients. In eight of them the preoperative ankle-brachial pressure index (ABI) was less than 0.4, but seven other patients with ABI less than 0.4 had maintained patency. In six of the ten with occlusion the toe-brachial pressure index (TBI) was less than 0.1, but in three others with TBI less than 0.1 the grafts were patent. During the first postoperative week there was progressive rise in pressure indices, reaching statistical significance on day 6, though with greatest rise on day 1. Although preoperative ABI less than 0.4 and TBI less than 0.1 were associated with high occlusion risk, the specificity of these indices was too low for predictive value. The repeated measurements during postoperative week 1 added no useful information to that obtained on day 1.

Aged↗
PubMed1994

HIV prevention: factors that predict compliance with testing and counseling procedures.

Human immunodeficiency virus (HIV) testing and pretest/posttest counseling are central components in prevention efforts in the United States. Yet, not all persons return for their test results and posttest counseling. Based on an exploratory study at four community health centers in South Florida, the authors determined the percentage of patients who returned to these clinics. They also examined those sociodemographic and HIV antibody test-related factors that predicted patient return. Less than 50% of those patients tested returned. Younger, urban, minority group patients whose HIV serostatus was likely to be negative were the least likely to return for test results. The authors describe a direction of future research to address these disturbing findings.

Adolescent↗
PubMed2004

Gait velocity in senior people. An easy test for detecting mobility impairment in community elderly.

BACKGROUND: Functional assessment is an important part of the evaluation of elderly patients. Mobility problems detected by functional tests predict the development of more severe disability and injurious events such as falls and hip fractures. Several tests to evaluate mobility have been described, but most of them are difficult to perform by a primary care physicians or take much time in the ambulatory setting. PURPOSE: To evaluate different mobility test to detect mobility impairment in community senior people. Select an easier test to perform on the ambulatory ward by a GP with the hypothesis that gait velocity could be an easier test to detect early mobility impairment. METHODS: A cohort of 100 elderly subjects of 75 year and older were selected from our database and contacted by phone. The subjects were appointed and assessed by three geriatricians from January to May 2000. The measures including MMSE, Yesavage Test, ADL (Barhtel) and IADL (Lawton), the Get Up and Go test, the POMA, one leg balance test and the Gait Velocity (GV). A gait velocity of 0.8 m/s or lower was defined as a pathological gait velocity (PGV). RESULTS: 95 subjects, mean age 79.63 (+/- 4) ranged form 75 to 95. Women in 71.3%. The ADLs were normal on 85% of the patients and the MMSE was normal on 78%. There was a significant association between pathological gait velocity (<0.8m/sec) and impairment on Get up and Go (OR 2.20; 95% CI 1.44-3.34), incapacity to perform the one leg balance test (OR 2.20; 95%CI: 1.43 - 4.71) and abnormal POMA test (OR 4.60; 95 %CI 1.5-14.7). Only 15% of the subjects with normal gait velocity reported recurrent falls in the previous 6 months while 35% of subjects with pathological gait velocity did. (OR 0.32 CI95% 010-099 p < 0.044). CONCLUSION: The pathological gait velocity (<0.8m/sec) correlates with a pathologic performance of Get Up and Go test and POMA and with the incapacity to perform the One Leg Balance test. Also correlate with previous repeated falls in the last 6 (p <0.04). The gait velocity could be a test easy to perform, no time consuming, and an operative tool to apply in the ambulatory care to detect elderly patients with mobility impairment.

Accidental Falls↗
PubMed1999

Sensitizing potential of acetaldehyde and formaldehyde using a modified cumulative contact enhancement test (CCET).

The contact allergenic activity of acetaldehyde was investigated with a modified cumulative contact enhancement test (CCET) method in guinea pigs. Possible cross-reactivity between acetaldehyde and formaldehyde was also studied. In contrast to the original CCET protocol, we used sham-treated controls and the chemicals were tested with closed epicutaneous application at 1st challenge. The suitability of the method was verified with formaldehyde and the results were comparable with those previously found with the guinea pig maximization test (GPMT). For the 1st time, acetaldehyde was shown to be a contact allergen in predictive tests. No cross-reactivity was observed between acetaldehyde and formaldehyde. Acetaldehyde seems to be a rare sensitizer in man. However, its allergenic activity should be considered, since it might be present as an impurity in ethoxylated surfactants. As the CCET protocol involves topical induction and challenge, we regard the modified version as well suited to evaluation of the contact allergenic potential of chemicals.

Acetaldehyde↗
PubMed1986

Results of sphincteroplasty in patients with spastic sphincter of Oddi. Predictive value of operative biliary manometry and provocation tests.

The predictive value of different preoperative provocation tests and operative biliary manometry was studied in a series of 22 patients undergoing sphincteroplasty for suspected spastic sphincter of Oddi (SPO). The result of the operation was good in 59%, 54%, and 71% of patients in groups with a positive codein test, a positive endoscopic retrograde cholangiopancreatography filling pain sign, and positive fentanyl test, respectively. Common bile duct pressure (CBDP) did not differ significantly between the SPO spasm group and control patients, but in the fentanyl test the CBDP elevation was significantly higher (p less than 0.01) than in controls (7.7 versus 3.3 mm Hg). It was concluded that the operative fentanyl test seems to be useful in predicting the response to surgery (sphincteroplasty) in patients with post-cholecystectomy biliary-type pain and suspected SPO spasm.

Adult↗
PubMed2000

Impact of genetic testing for Huntington disease on the family system.

The psychological impact of DNA predictive testing on asymptomatic individuals at risk for Huntington disease (HD) has received considerable attention since the advent of the procedure in 1993. This study examined the impact of such testing on families from the families' perspective. Individuals asymptomatic at the time of testing, together with their families, were interviewed in their homes with a semi-structured interview. Eighteen families with a total of 55 individuals participated. Defining the family as the unit of analysis was consistent with Systems Theory that links interactions of individuals, families, and the social environment. Areas of affected family functioning noted by the respondents included: 1) family membership; 2) family patterns of communication; and 3) future care giving concerns as they influenced current relationships. Eighty-one percent of families experienced changes in family membership. Members in 50% of families experienced changes in patterns of communication, and 56% percent of persons reported changes in current relationships in response to test results and their implications for future caregiving. The data support the conclusion that genetic testing is a family, as opposed to an individual, matter and that family involvement in the decision making process should be strongly encouraged in order to help families adjust. The data imply that families will benefit in pre-test sessions from an examination of their patterns of dealing with illness issues, both past and present.

Adult↗
PubMed2006

Grey matter changes can improve the prediction of schizophrenia in subjects at high risk.

BACKGROUND: We hypothesised that subjects at familial high risk of developing schizophrenia would have a reduction over time in grey matter, particularly in the temporal lobes, and that this reduction may predict schizophrenia better than clinical measurements. METHODS: We analysed magnetic resonance images of 65 high-risk subjects from the Edinburgh High Risk Study sample who had two scans a mean of 1.52 years apart. Eight of these 65 subjects went on to develop schizophrenia an average of 2.3 years after their first scan. RESULTS: Changes over time in the inferior temporal gyrus gave a 60% positive predictive value (likelihood ratio >10) of developing schizophrenia compared to the overall 13% risk in the cohort as a whole. CONCLUSION: Changes in grey matter could be used as part of a predictive test for schizophrenia in people at enhanced risk for familial reasons, particularly for positive predictive power, in combination with other clinical and cognitive predictive measures, several of which are strong negative predictors. However, because of the limited number of subjects, this test requires independent replication to confirm its validity.

Brain↗
PubMed1989

Bahia grass pollen, a significant aeroallergen: evidence for the lack of clinical cross-reactivity with timothy grass pollen.

Thirty-eight subjects were challenged (25 nasal, 13 bronchial) with Bahia grass, Paspalum notatum, pollen extract. A positive Bahia intradermal skin test predicted a positive challenge to Bahia in all (11/11) of the nasal challenges and 75% (6/8) of the bronchial challenges. All 19 subjects with negative Bahia intradermal skin tests had negative challenges with Bahia. Specific IgE antibodies to Bahia pollen were detected by conventional RAST (greater than or equal to 2+) in 82% (14/17) of subjects with positive challenges and in 5% (1/20) of subjects with negative challenges. Eight subjects had positive intradermal skin tests to either Bahia (three) or timothy, Phleum pratense (five). Seven of the eight subjects reacted exclusively to either Bahia or timothy nasal challenge as predicted by their skin tests. Bahia grass is a significant aeroallergen, which in some subjects can be demonstrated not to cross-react with timothy.

Allergens↗
PubMed1996

Home ovulation testing in a donor insemination service.

The use of home ovulation testing kits in donor insemination (DI) has been proposed to increase patient and clinic convenience while not compromising fecundity rates. Such a system was introduced into our DI service in December 1994, and we here report an audit of experience over 6 months. Patients were offered home or laboratory luteinizing hormone (LH) testing, and those requesting home testing were asked to store an aliquot of tested urine for subsequent assay in the laboratory allowing retrospective analysis of the accuracy of cycle timing. Insemination using cryopreserved semen was performed on the day home testing predicted ovulation, or on the day an LH surge was detected in the laboratory, and on the following day. Pregnancy rates were significantly reduced in home testers: 3.4% per cycle (174 cycles, 64 women) versus 12.7% (110 cycles, 53 women) over the same time period (P < 0.005, 95% confidence interval 6.5-18.9). Urine samples from 140 cycles from 51 women using home testing were analysed. There were insufficient data in nine to allocate the cycle. Of home tested cycles, 37 (28%) were inseminated on a day other than the first day of the LH surge. In 13 of these insemination was performed after the first day of the LH surge. Incorrect treatment was associated with high baseline LH, but those with 'late' treatment had low basal LH concentrations, similar to those correctly treated. Analysis of individual urine samples showed that the positive predictive value of home testing was 72%. These results suggest that home ovulation testing results in reduced chance of pregnancy, with increased frustration for both patients and clinic staff. This may be particularly so in women with high baseline LH concentrations.

Adult↗
PubMed1992

QROC curves and kappa functions: new methods for evaluating the quality of clinical decisions.

The application of statistical methods for measuring the ability of clinical judgements and tests to discriminate between normal and diseased patients is increasing in optometry and ophthalmology. This paper presents two new methods for assessing the quality of such diagnostic decisions. Both are based on measurement of the kappa coefficient of association and offer theoretical and practical advantages over traditional methods. The paper first introduces the family of kappa coefficients with examples of their calculation and application. The use of weighted kappa values for measuring test sensitivity and specificity is explained, and it is shown how the results may be plotted in the form of the QROC curve which enables different aspects of test discriminability to be represented graphically. Kappa functions are then proposed as an alternative method for representing and predicting test performance, having the advantage of identifying optimal test criteria in addition to providing measures of discriminability. The clinical application of the new methods is illustrated using data for the detection of glaucoma from measurements of intraocular pressure.

Eye Diseases↗
PubMed2000

Huntington's Disease.

Huntington's disease is a neurodegenerative disorder inherited in an autosomal dominant fashion that results in involuntary movements, psychiatric symptoms, and cognitive dysfunction. The illness typically begins in midlife and progresses over 15 to 20 years, producing increasing disability. The diagnosis of Huntington's disease in an individual has implications for family members as well, whose at-risk status may be altered by the diagnosis. Genetic counseling and information about alternative approaches (eg, clinical diagnosis, DNA banking) should be provided and consent obtained before DNA testing in a symptomatic patient. Genetic counseling is essential for predictive testing in asymptomatic at-risk individuals. Although disease-modifying therapy is not yet available, a multidisciplinary approach to both pharmacologic and nonpharmacologic management can improve the motor and psychiatric symptoms of the illness and enhance function and quality of life for patients and their families. There have been few rigorous trials of treatments for Huntington's disease. The medications discussed in this article have been empirically found to be useful in the management of specific symptoms. Therapy for the movement disorder should focus on those symptoms that specifically limit function. The potential contribution of medication side effects to disability should be periodically reassessed and therapy adjusted as the disease progresses. Psychiatric symptoms are a substantial source of morbidity in this disorder and should be actively treated because they are often quite responsive to appropriate therapy. Both the motor and the psychiatric symptoms can be modified by environmental as well as pharmacologic strategies. Ongoing assessment of the need for adjunctive therapies by means of physical, occupational, and speech therapy is an important component of management, and social work intervention is often necessary to assist with the practical difficulties faced by patients and caregivers. Voluntary organizations are an important source of information and support for professionals caring for patients with Huntington's disease as well as for patients and their families.

Journal Article↗
PubMed1997

Can 24-hour ambulatory blood pressure measurement predict the development of hypertension in primigravidae?

OBJECTIVE: To assess the role of 24-hour ambulatory blood pressure measurement in the mid-second trimester as a predictive test for the development of hypertension in pregnancy. DESIGN: Prospective intervention. SETTING: The Rotunda Hospital, Dublin. PARTICIPANTS: One thousand one hundred and two healthy primigravid women. INTERVENTION: 24-hour ambulatory blood pressure measurement at 18 to 24 weeks of gestation. MAIN OUTCOME MEASURES: The development of pre-eclampsia or gestational hypertension. RESULTS: A total of 1048 women had sufficient readings to be included in the final analysis. Of these, 23 (2.2%) developed pre-eclampsia, 64 (6.1%) developed gestational hypertension and 961 (91.7%) remained normotensive. Significantly higher ambulatory blood pressures were recorded in both the pre-eclamptic and gestational hypertensive group compared with the normotensive group. In addition, the gestational hypertensive group had significantly higher clinically measured blood pressure compared with the normotensive group. There were no differences between the pre-eclamptic and the gestational hypertensive group for any of the blood pressure parameters analysed. The best overall predictor for pre-eclampsia was 24-hour mean diastolic pressure which using a cutoff level of 71 mmHg gave a test with a sensitivity of only 22% and a positive predictive value of 15%. CONCLUSION: Because the absolute differences are small and the overlap between the hypertensive and normotensive groups large, ambulatory blood pressure measurement, in a healthy primigravid population, between 18 and 24 weeks of gestation is not a useful predictor of hypertension.

Adult↗
PubMed2000

In vitro and human testing strategies for skin irritation.

Prior to the manufacture, transport, and marketing of chemicals or products, it is critical to assess their potential for skin toxicity (corrosion or irritation), thereby protecting the worker and consumer from adverse skin effects due to intended or accidental skin exposure. Traditionally, animal testing procedures have provided the data needed to assess the more severe forms of skin toxicity, and current regulations may require animal test data before permission can be obtained to manufacture, transport, or market chemicals or the products that contain them. In recent years, the use of animals to assess skin safety has been opposed by some as inhumane and unnecessary. The conflicting needs of the industrial toxicologist to (1) protect human safety, (2) comply with regulations, and (3) reduce animal testing have led to major efforts to develop alternative, yet predictive, test methods. A variety of in vitro skin corrosion test methods have been developed and several have successfully passed initial international validation. These have included skin or epidermal equivalent assays that have been shown to distinguish corrosive from noncorrosive chemicals. These skin/epidermal equivalent assays have also been modified and used to assess skin irritation potential relative to existing human exposure test data. The data show a good correlation between in vitro assay data and different types of human skin irritation data for both chemicals and consumer products. The effort to eliminate animal tests has also led to the development of a novel human patch test for assessment of acute skin irritation potential. A case study shows the benefits of in vitro and human skin irritation tests compared to the animal tests they seek to replace, and strategies now exist to adequately assess human skin irritation potential without the need to rely on animal test methods.

Animals↗
PubMed2001

Platelet tests in the prediction of myocardial infarction and ischaemic stroke: evidence from the Caerphilly Prospective Study.

A platelet test that is predictive of myocardial infarction (MI) and/or stroke would enable the targeting of anti-platelet drugs towards high-risk patients. The predictive power of several platelet tests for MI and for stroke was examined in 2000 older men in the Caerphilly Cohort Study of Heart Disease, Stroke and Cognitive Decline. The tests were: aggregation to adenosine diphosphate (ADP) in platelet-rich plasma (PRP); aggregation to ADP in whole blood measured using an impedance method and a test of platelet aggregation induced in whole blood by high-shear flow. Around 200 MIs and 100 ischaemic strokes occurred during a 10-year follow-up. Neither primary nor secondary aggregation in PRP was predictive of MI. However, the fifth of men in whom the primary response to ADP was least, showed the highest risk of a subsequent stroke [relative odds (RO) 1.64; 95% confidence interval (CI) 1.12-2.43]. Aggregation in whole blood was not predictive of MI but, again, the fifth of men with the least platelet response showed the highest stroke incidence (RO 1.79; 95% CI 1.06-3.00). Retention of platelets in the high-shear test was not predictive of either event.

Adenosine Diphosphate↗
PubMed1986

[Prognostic criterion in the mendelian analysis of quantitative traits].

Prediction test for estimation of genetical parameters and the fitness of the hypothesis is proposed. The test is based on coincidence of values of quantitative character in individuals predicted on the basis of the genetic analysis and the empirical measured values. The method gives a higher correctness of prediction of phenotypical values than statistical methods. The problem of a choice of the boundary values for the test is considered.

Genetics, Medical↗
PubMed2000

Testicular volume does not predict germ cell count in patients with cryptorchidism.

PURPOSE: A germ cell count of less than 0.2 germ cell per tubule on the prepubertal biopsy of cryptorchid testes predicts abnormal spermiograms and decreased fertility in adulthood, and may be used to select patients for post-orchiopexy hormonal therapy. Testicular volume directly correlates with testicular function and spermiogenesis. We determined whether testicular volume would predict the total germ cell count accurately enough to replace testicular biopsy in the modern management of cryptorchidism. MATERIALS AND METHODS: At our hospital 723 patients younger than 9 years with cryptorchidism (unilateral in 619 and bilateral in 104) underwent orchiopexy and bilateral testicular biopsies. These patients had not undergone groin surgery or hormonal therapy previously and had at least 50 tubules in each testicular biopsy. Testicular volume and position, patient age and germ cell counts were analyzed. The generalized estimating equation was used to determine whether a correlation existed between testicular volume and germ cell count. RESULTS: The generalized estimating equation demonstrated a direct correlation between testicular volume and germ cell count. However, germ cell counts predicted from testicular volume varied widely within the 95% confidence intervals. Testes with less than 0.2 germ cell per tubule cannot be reliably distinguished from those with greater than 0.2 germ cell per tubule. CONCLUSIONS: Testicular volume does not accurately predict the germ cell count in patients with undescended testes, cannot be used to select patients for post-orchiopexy hormonal therapy and cannot replace testicular biopsy in the modern management of cryptorchidism.

Child↗