Cardiac screening procedures

Seven per cent of a sample group of civil service employees were found to have diagnosable heart disease. The diagnosis was made on the basis of a complete physical examination and history taken by a specialist in internal medicine and/or heart disease. In addition a questionnaire form related to symptoms of heart disease was filled out by the patient, and various laboratory tests were made. As a technique in cardiac case-finding, the electrocardiogram was the best single device. Of all the cases of heart disease in this survey 65 per cent were detected from tracings obtained by using all 12 leads, and 57 per cent if only the three standard limb leads were taken; but of the presumably normal persons, 13 per cent would be erroneously suspected of possible heart disease by this technique. Heart disease was detected in 50 per cent of the diagnosed cases on the basis of answers to three of the questions in the questionnaire. Eighteen per cent of normal persons would also have been suspected of having heart disease by this case-finding device. Although the survey reported did not develop a simple cardiac case-finding technique, the data presented indicated that a questionnaire history-form, if judiciously used and evaluated, may be of value to physicians who examine large numbers of patients who are unwilling to submit to a complete cardiac evaluation.     

Recording and interpretation of the results obtained by using the ELISA Sevatest commercial immunoenzyme kit for detecting Toxoplasma gondii antibodies

The results of the repeated tests of 295 serum samples from patients, previously examined by means of enzyme immunoassay screening and traditional serological tests (complement fixation, indirect immunofluorescence, and indirect hemagglutination) and 115 serum samples from healthy donors, studied by enzyme immunoassay techniques with the use of the commercial kits Sevatest ELISA, have been analyzed. The methodological approach permitting the determination of the final titer of the serum under study, taken in a dilution of 1:800, by its optical density has been used. The mean geometric titer for the control group of donors, determined in the enzyme immunoassay, has been 1:800. This fact suggests that titers exceeding 1:1,600 should be considered diagnostically significant.     

The Chilliwack Respiratory Survey, 1963: Part IV. The Effect of Tobacco Smoking on the Prevalence of Respiratory Disease

Chronic non-specific respiratory disease was found by a survey at Chilliwack, B.C., to affect 29.3% of men and 18.0% of women between the ages of 25 and 74. The habit of current cigarette smoking was found to be the most important single factor associated with respiratory disease, and was found to be related to changes in simple measures of lung function. The authors were unable to confirm the existence of a threshold in lifetime cigarette smoking before respiratory disease occurred.Comparisons were made with a population previously studied at Berlin, New Hampshire, U.S.A., in 1961. At Berlin, where pollution by SO₂ and dust-fall had been thoroughly documented, the comparable prevalence rates for respiratory disease were 40.0% for men and 21.6% for women. When differences between the two populations as to age and number of cigarettes smoked daily were taken into account, the disease rates in these two communities were found to be quite similar. The Chilliwack sample did, however, have significantly higher values for the lung function tests.     

Coronary Artery Disease with Single Coronary Artery

The authors have reviewed the literature in search of the coexistence of single coronary artery with significant coronary artery disease. Two cases of single right coronary artery are described. In both, the anomalies were unsuspected and diagnosed roentgenographically in life. Both patients had angina pectoris, positive graded-exercise stress tests, and hemodynamically significant obstruction or occlusion to the coronary arteries. In neither case was the stenosis proximal or amenable to bypass surgery.     

Mutation screening of EXT genes in Chinese patients with multiple osteochondromas

Since vascular risk factors commonly act for susceptibility to Alzheimer's disease (AD) and vascular dementia (VaD) by declining cognitive abilities, we conducted a genetic association study to identify their common underlying genetic factors. We selected single nucleotide polymorphisms (SNPs) which had been previously discovered for association with AD, and case and control associations of VaD were examined with the individual SNPs using 207 patients with VaD and 207 sex- and age-matched control subjects. As a result, no significant associations of susceptibility to VaD with 13 selected SNPs were observed even without employing a multiple test (P>0.05). This study suggests that genetics of VaD might be quite different from that of AD, and cautions should be taken especially when inferences about genetic factors are made with patients with mixed dementia.     

The Scarborough Glaucoma Survey

A glaucoma screening survey was carried out in Scarborough, Ontario, to detect previously unsuspected cases of the disease.General practitioners were employed to perform Schiotz tonometry. Suspected cases were further tested with applanation tonometry and tonography with water drinking.Of the 17,968 persons examined, 999 had a family history of glaucoma. Forty-one of these had obvious clinical glaucoma. The use of Schiotz tonometry plus applanation tonometry in individuals with a positive family history uncovered 463 suspected of having glaucoma. Tonography with water drinking revealed 348 persons with abnormal findings. Of this number, 228 had clinical glaucoma and 120 preclinical glaucoma.Mass screening by tonometry was found to be valuable in detecting glaucoma in the early stages. In most instances, blindness from this disease can be prevented by early diagnosis.     

Dexpramipexole Is Ineffective in Two Models of ALS Related Neurodegeneration

Treatment options for people living with amyotrophic lateral sclerosis (ALS) are limited and ineffective. Recently, dexpramipexole (RPPX) was advanced into human ALS clinical trials. In the current studies, we investigated RPPX in two parallel screening systems: 1) appropriately powered, sibling-matched, gender-balanced survival efficacy screening in high-copy B6-SJL-SOD1^G93A/Gur1 mice, and 2) high-content neuronal survival screening in primary rat cortical neurons transfected with wild-type human TDP43 or mutant human TDP43. In both cases, we exposed the test systems to RPPX levels approximating those achieved in human Phase II clinical investigations. In SOD1^G93A mice, no effect was observed on neuromotor disease progression or survival. In primary cortical neurons transfected with either mutant or wild-type human TDP43, a marginally significant improvement in a single indicator of neuronal survival was observed, and only at the 10 µM RPPX treatment. These systems reflect both mutant SOD1- and TDP43-mediated forms of neurodegeneration. The systems also reflect both complex non-cell autonomous and neuronal cell autonomous disease mechanisms. The results of these experiments, taken in context with results produced by other molecules tested in both screening systems, do not argue positively for further study of RPPX in ALS.     

Amoebiasis: diagnosis by aspiration and exfoliative cytology

The present study was undertaken to evaluate the use of fine needle aspiration and exfoliative cytology in the identification of amoebic cysts/trophozoites, and to characterize amoebiasis. The subjects consisted of 15 patients, 11 diagnosed by fine needle aspiration cytology (FNAC) as amoebic abscesses (14 liver and one pulmonary) and four women whose cervical smears contained Entamoeba histolytica cysts or trophozoites. Of 128 ultrasonographically guided FNAC of hepatic lesions over a four year period, 17 were abscesses of which 10 were diagnosed as amoebic. A single case of pulmonary amoebiasis was detected in an 18-year-old male. The case was initially diagnosed as tubercular due to deceptive symptomatology. Three cases of amoebic cysts and one trophozoite were reported on routine cervical smear screening. All four cases were unsuspected for amoebic infection. The disease may easily go undetected unless meticulous screening is exercised, and the search for cysts or trophozoites is made with clear concepts of the morphological characteristics of E. histolytica in mind.     

Molecular heterogeneity in the infantile and juvenile forms of Sandhoff disease (O-variant GM2 gangliosidosis)

There are two major beta-hexosaminidase, EC 3.2.1.52, isozymes in normal human tissues. They exist as active dimers of alpha- and/or beta-subunits. A defect of their beta-subunit results in Sandhoff disease (O-variant GM2 gangliosidosis), an inherited, clinically heterogeneous, lysosomal storage disease. The status of the HEXB gene, pre beta-polypeptide chain mRNA, and residual beta-hexosaminidase activities were examined in a clinically and ethnically diverse collection of 16 fibroblast cell lines from patients with Sandhoff disease. Differentiation of the two major clinical types, infantile and juvenile onset, could be made by the determination of the activity of the residual beta-hexosaminidase eluting in the same pH range as hexosaminidase A. All the juvenile lines were found to have normal or reduced levels of pre beta-chain mRNA and no gross abnormalities in the HEXB gene. Of the 11 infantile type cell lines examined, four were found to contain no detectable pre beta-chain mRNA. Two cell lines in this group contained partial gene deletions localized to the 5' end of the HEXB gene. One of these cell lines has previously been assigned to the single complementation group in Sandhoff disease, conclusively demonstrating that the primary gene defect in the majority of Sandhoff cases is in the HEXB gene itself. These data suggest that each clinical group is made up of a collection of different HEXB mutations.     

Identification of a WSSV neutralizing scFv antibody by phage display technology and in vitro screening

White spot syndrome virus (WSSV) is one of the most significant viral pathogens causing high mortality and economic damage in shrimp aquaculture. Although intensive efforts were undertaken to detect and characterize WSSV infection in shrimp during the last decade, we still lack methods either to prevent or cure white spot disease. Most of the studies on neutralizing antibodies from sera have been performed using in vivo assays. For the first time, we report use of an in vitro screening method to obtain a neutralizing scFv antibody against WSSV from a previously constructed anti-WSSV single chain fragment variable region (scFv) antibody phage display library. From clones that were positive for WSSV by ELISA, 1 neutralizing scFv antibody was identified using an in vitro screening method based on shrimp primary lymphoid cell cultures. The availability of a neutralizing antibody against the virus should accelerate identification of infection-related genes and the host cell receptor, and may also enable new approaches to the prevention and cure of white spot disease.     

A case-control study of cervical cancer screening in north east Scotland.

To estimate the relative risk of invasive cervical cancer in each succeeding year after a negative screening result the screening records of all women tested in the north east of Scotland were examined as the basis for a case-control study. The cases consisted of 115 women in whom invasive cervical cancer had been diagnosed in 1968-82 and who had appeared in the screening records at least once before diagnosis. For each patient five controls were selected from women of the same age who appeared in the screening records before the date of diagnosis in the patient. If the patient''s cancer had been detected by screening the controls were chosen from women of the same age screened the same year. A comparison was made between cases and controls of the number of negative smears taken before the diagnosis. The results showed a high relative protection (inverse of the relative risk) in the first two years after a negative test, falling steadily as time since the last negative test elapsed. Even after 10 years, however, a considerable residual effect was observed.     

Mammography screening in the county of Fyn. November 1993-December 1999

This report covers the outcome of the first three invitation rounds of the organised mammography screening programme in the county of Fyn. The programme started in November 1993, and the third invitation round ended on 31 December 1999. The screening takes place either at a special clinic located at University Hospital Odense or in a mobile unit. Women living in and around the city of Odense are examined at the clinic (about 55%), while the rest are examined in the mobile unit. Two-view mammography is used at the first screening. Women with dense breast tissue will continue to have two-view mammography (about 60%), whereas the rest will have singleview mammography at the subsequent screens. All screening images are exposed at the mammography-screening clinic and evaluated with double reading in the clinic. The programme targets women aged 50-69, except those undergoing treatment for breast cancer or going for regular check-ups following breast cancer. Based on the updated population register, the IT-Centre of the county of Fyn issues the invitations. Invited are all women aged 50-69 and living in the county of Fyn when their general practitioners' patients are invited. During the first 3 invitation rounds, 136,079 screening tests were made. Of these, 129,375 tests were made in the women aged 50-69 targeted by the programme. In addition, 6682 screening tests were made in women aged 70 and above, and 22 screening tests were made in women below the age of 50. As a consequence of the mammography screening 2657 assessments were made, 1145 women had surgery, 782 women were diagnosed with invasive breast cancer, and 109 women were diagnosed with ductal carcinoma in situ. A participation rate for the first invitation round was calculated immediately after the end of the round based on the number of participants divided by the number of women invited. This percentage was 88%. Invitation data are, however, not stored. It is therefore not possible now to calculate the participation rates in previous invitation rounds based on the same method. We have therefore chosen to calculate the participation rate as the coverage, i.e. the number of participants divided by the average number of women in the county of Fyn during a given invitation round. Calculated in this way, 84% participated in the first round, 84% in the second round, and 82% in the third round. It should be remembered that these figures do not take into account that some women are not invited because they 1) were undergoing current treatment for breast cancer or going for regular check-ups following breast cancer, or 2) did not participate in the previous round (and never actively informed the programme that they wanted an invitation to the next invitation round), relevant only for the second and third invitation round. For the second and third invitation rounds, the programme only invited women who participated in the previous invitation round, asked the clinic for an invitation, or entered the target population since the last invitation round. Therefore the participation rate in the second invitation round among actually invited women will be close to 94%, as 94% of those participating in the first round came for the second round. For the third invitation round, the participation rate among actually invited women will be close to 96%, as 96% of those participating in the first and second rounds came for the third round. One per cent of the participants in the first invitation round were diagnosed with invasive breast cancer or ductal carcinoma in situ. The detection rate was 0.5% in both the second and third invitation rounds. Ductal carcinoma in situ cases constituted 14% of the detected cases in the first and second rounds, and 10% in the third round. The percentage of invasive breast cancer 10 mm of less was 38%, 31%, and 32%, respectively, and 68%, 74%, and 73%, respectively, were node-negative. The screening programme of the county of Fyn fulfilled all the quality assessment parameters specified by the European guidelines on breast cancer screening, except two. The proportionate interval cancer rate was higher than specified in the guidelines, probably mainly due to the fact that the Fyn programme operates without early recalls. The proportion of stage II+ cancers was higher than specified in the guidelines, which seems, however, to be due to inconsistency between some of the performance indicators in the European guidelines. This analysis of the outcome from the first three invitation rounds of the mammography screening programme in the county of Fyn thus showed that it is a programme of high quality with a favourable profile of the prognostic indicators. The screening programme is hopefully well on its way to reducing breast cancer mortality in the county of Fyn.     

Screening for squamous cervical cancer: duration of low risk after negative results of cervical cytology and its implication for screening policies. IARC Working Group on evaluation of cervical cancer screening programmes.

A collaborative study of screening programmes in eight countries was performed to estimate the risks of cervical cancer associated with different screening policies. Most of the data came from centrally organised screening programmes. Relative protection was higher in women who had had two or more negative results of screening tests than in those who had had only one negative smear, particularly in the first five years after the last test. There was little difference in the protection afforded by screening every year compared with every three years, but screening only once every five or 10 years offered appreciably less protection. The age of the women did not affect the sensitivity of the test or the sojourn time of the disease (the length of the detectable preclinical phase during which abnormal cytology could be picked up if a smear were taken); invasive cancer in women under 25 was rare. Centrally organised screening programmes were more effective than uncoordinated screening. Screening programmes should be aimed principally at women aged 35-60 but should start some years before the age of 35, and the intervals between screening should be three years or less.     

Screening tests for diabetes detection; combined with a chest x-ray survey

A program was carried out to test the value and feasibility of performing blood sugar screening tests in conjunction with a community-wide chest x-ray survey. A simple, rapid and inexpensive blood sugar screening test requiring only about two drops of blood from the finger tip was used. Among 14,681 persons who stated that they did not have diabetes, 191 or 1.3 per cent had "positive" results in screening tests. The number of persons referred to their physicians for diagnostic study because of the possibility of diabetes was reduced from 191 to 127 by means of a more specific secondary screening test. Diagnostic information with regard to 102 of the 127 persons referred to their physicians was supplied by the physicians. In 58 (0.40 per cent of the 14,681 participants) the diagnosis was diabetes-newly discovered as a result of referral by the survey.Some of the persons referred to their physicians because of suspicion of diabetes, while not then diabetic, might be considered prediabetic. The appearance of diabetes in this group during the year following the survey was therefore investigated. Glucose tolerance tests were performed for 32 of the diabetes suspects whose diagnosis immediately following the survey was either "not diabetic" or unknown. In 15 cases the glucose tolerance curves were indicative of diabetes, in seven cases questionable and in ten cases normal. The 58 persons diagnosed immediately after the survey plus the 15 found to have "diabetic" glucose tolerance curves a year later made a total of 73 newly discovered diabetics. This is a discovery rate of 0.50 per cent among the 14,681 participants in the survey. The success of this combined diabetes detection and chest x-ray survey suggests that other screening procedures should be studied to determine the desirability of adding them to similar community-wide case-finding programs.     

Is pulse oximetry a reliable tool for detection of aspiration?

This study was designed to determine whether significant differences in saturation levels existed among patients with aspiration and patients without and wether pulse oximetry can reliably detect aspiration in patients with dysphagia. We also examined the effects of gender and disease (neurologic versus non neurologic) on saturation levels. We studied 38 patients. They all underwent a videofluoroscopic study of swallowing (VFSS). Twenty patients aspirated on videofluoroscopic study of swallowing: ten patients were solid aspirators, ten patients were liquid aspirators. In each group (liquid aspirators, solid aspirators or non aspirators) we found no significant difference in saturation levels. We found however a significant difference in saturation levels between each group before, during and after videofluoroscopic study of swallowing. Both gender and disease had an effect on saturation levels. We conclude that pulse oximetry can not serve as a screening tool for detection of aspiration as saturation levels are dependent on many factors. Therefore one can not reliably predict aspiration with a single saturation screening.     

Celiac disease: Pathogenesis and serologic tests

The serological tests represent a significant advance in screening at-risk patients for celiac disease and probably should supplant other nonspecific methods for screening, such as 72-hr fecal fat, the d-xylose test, serum carotene, or small-bowel x-ray. The latter tests lack sensitivity, specificity, or simplicity. The published results suggest that the EMA IgA IFA is currently the screening tool of choice. The demonstration of the characteristic histological abnormalities of the intestinal abnormality and clinical improvement on a gluten-free diet is the gold standard for the diagnosis of celiac disease. Whether serological testing can substitute for intestinal biopsy in the diagnosis of celiac disease will depend on the experience obtained from more widespread application of these tests. The greater availability and more frequent use of these tests should increase the detection of a readily treatable condition, the diagnosis of which is often greatly delayed.     

A Comparative Study of the Triphenyltetrazolium Chloride (Uroscreen) Test and Conventional Methods for the Detection of Bacteriuria

Acute urinary tract infection may be preceded by and active pyelonephritis may be associated with asymptomatic bacteriuria. Treatment of asymptomatic bacteriuria may prevent or arrest active, chronic pyelonephritis and its sequelae. Consequently, there is a need for a reliable and simple screening procedure to detect asymptomatic bacteriuria in large segments of the population.The reliability and practicability of tests advocated for the detection of bacteriuria, including the new chemical triphenyltetrazolium chloride (T.T.C.) (Uroscreen) test, were evaluated. Reliability was assessed by correlating results of these tests with bacterial counts of tested urines. Significant bacteriuria is defined as the presence of 100,000 or more organisms per ml. of urine.The T.T.C. (Uroscreen) test was positive in 92.5% of cases of bacteriuria; there were 7.5% false-negative and 2.8% false-positive results. Bacteria on Gram-stained smear were found in 95.5% of the cases of bacteriuria and in 14.6% of those with non-infected urine; pyuria (more than three leukocytes per high-power field), in 60% of those with bacteriuria and in 15.9% of those with presumably non-infected urine. Bacteria were conspicuous in the urinary sediment in 91.1% of cases of bacteriuria and in 3.7% of presumably non-infected urines.The T.T.C. (Uroscreen) test fulfilled the criteria for a reliable and simple screening procedure. It should be used concomitantly with other screening tests when the urine is examined routinely.     

Human papillomavirus DNA and liquid-based cervical cytology cotesting in screening and follow-up patient groups

OBJECTIVE: To compare the use of human papillomavirus (HPV) DNA and cervical cytology cotesting in screening and follow-up of patients with previous cervical abnormalities and to assess the significance of a positive HPV DNA test result in re-screening of cytologically normal cases. STUDY DESIGN: Cellular samples collected in liquid-based fixative were used for both cervical cytology and HPV DNA testing. The cervical cytology slides were manually screened by cytotechnologists followed by rapid re-screening by pathologists. The HPV DNA tests were performed using hybrid capture test kits. Statistical analyses of cervical cytology results and HPV DNA tests for high- and low-risk HPV from both patient groups were carried out. RESULTS: The prevalence of HPV DNA-positive cases was higher in younger patients. There was a poor correlation between cervical cytology results and HPV DNA tests for the screening group (kappa = 0.23), but a fair to good correlation was obtained for the follow-up group (kappa = 0.51). The false negative fraction of cytology negative/HPV DNA positive cases (0.1317), as compared with cytology negative/HPV DNA negative cases (0.0056), was statistically significant (p = 0.000001). CONCLUSION: The prevalence of HPV DNA decreased with increasing age in both the screening and follow-up patient groups. Virus clearance was delayed in the follow-up group as compared with the screening group. There was a poor correlation between cervical cytology and HPV DNA tests in the screening group but a fair to good correlation in the follow-up patient group. Cotesting of HPV DNA and cervical cytology increases the sensitivity and decreases the false negative fraction, suggesting that cotesting could be used to increase the interval of screening.     

Diagnostic Procedures in Sarcoidosis

One hundred consecutive patients suspected of having sarcoidosis were examined by means of available diagnostic procedures and the results of the examinations were compared. While Kveim tests and/or lymphocyte transformation tests gave the most significant results in cases of less than two years'' standing, a combination of these and organ biopsies is required for the diagnosis of cases of more than two years'' duration.An interpretation of the immunological deviations observed in sarcoidosis is attempted on the basis of observations made on leukocyte cultures and on isolations of mycobacteriophages from patients with sarcoidosis.     

Self testing for diabetes mellitus.

OBJECTIVE--To develop a simple, economically viable, and effective means of population screening for diabetes mellitus. DESIGN--A postal request system for self testing for glycosuria with foil wrapped dipsticks. Preprandial and postprandial tests were compared with a single postprandial test. The subjects were instructed how to test, and a result card was supplied on which to record and return the result. All those recording a positive test result and 50 people recording a negative result were invited for an oral glucose tolerance test. SETTING--General practice in east Suffolk, list size 11534. PATIENTS--All subjects aged 45-70 years registered with the practice were identified by Suffolk Family Health Services Authority (n = 3057). The 73 subjects known to have diabetes from the practice''s register were excluded, leaving 2984 subjects, 2363 (79.2%) of whom responded. 1167 subjects completed the single test and 1196 the two tests. MAIN OUTCOME MEASURES--Response rate and number of patients with glycosuria. Sensitivity, specificity, and positive predictive value of a single postprandial test and preprandial and postprandial tests. Number of new cases of diabetes identified and cost of screening. RESULTS--Of the patients completing the single postprandial test, 29 had a positive result, an oral glucose tolerance test showed that eight (28%) had diabetes, six (21%) impaired glucose tolerance, and 14 (48%) normal glucose tolerance. 44 of the group who tested before and after eating had a positive result; nine (20%) had diabetes, five (11%) impaired tolerance, and 26 (11%) normal tolerance. Screening cost 59p per subject and 81 pounds per case detected. Of the 17 people with previously undiagnosed diabetes, eight were asymptomatic and 11 had not visited their general practitioner in the past three months. CONCLUSIONS--A postal request system for self testing for postprandial glycosuria in people aged 45-70 is a simple and effective method of population screening for diabetes mellitus.