Analysis of false-negative and underreported smears in the Florence district screening program for cervical carcinoma

AIMS AND BACKGROUND: To review false-negative or underreported (reactive changes, squamous or glandular atypia) smears performed in women developing histologically proven CIN2 or more severe lesions within 24 months and evaluate error causes. The study setting was the Florence District cervical cancer population-based screening: about 60,000 women age 25-60 years screened per year. METHODS: 118 false-negative or underreported cases were identified at screening files-cancer Registry matching, and the original smears were reviewed by six independent readers to judge smear adequacy and error type. RESULTS: Sampling errors (reported as inadequate, negative or less severe than CIN1 at review) accounted for 74% and screening/interpretation errors (reported as CIN1 or more severe at review) accounted for 26% of studied cases. Screening/interpretation errors were more likely ascribed to misinterpretation and underreporting than to misperception of cellular abnormalities. CONCLUSIONS: Quality control should above all address the problem of sampling adequacy. Due to the rarity of misperceived abnormalities (true screening errors), manual or automated rescreening of negative smears would not be an effective procedure for quality control.     

Single-specimen bile cytology: a prospective study of 80 patients with obstructive jaundice

The interaction between drugs (tolbutamide (1), 1-butyl-3-(methylsulfonyl)urea (2)) and human serum albumin (3) was investigated by equilibrium dialysis and NMR spectroscopy. The binding of 1 and 2 to 3 was concluded to be hydrophobic and hydrophilic, respectively, on the basis of the dependence of the binding constants on temperature, ionic strength, and chain length of fatty acid added. In 1H-NMR spectra of 1, there were no significant shifts with change in concentration or addition of 3. The spin-lattice relaxation time (T1) and spin-spin relaxation rate (1/T2) of the respective protons of 1 were independent of concentration, but depended on the concentration of 3 added. The binding position was determined from the ratio of 1/T2 of 1 bound to 3 and free 1. 1 and 2 were found to bind to 3 through the tolyl group and sulfonylurea group, respectively. The binding property of 1 was considered to be governed by the competition between the hydrophobic effect of the tolyl group and the hydrophilic effect of the sulfonylurea group in the molecule.     

Cervical cytology screening: experience of a general hospital

At Henderson General Hospital, Hamilton, a program was introduced whereby cervical smears were taken routinely for cytologic study from all women admitted aged 17 years or older. The procedure was performed by a specially trained nurse. In a 5-year period 53% of eligible patients were screened. Of these, 32% had not had a cervical smear taken before. In 7681 smears nine instances of invasive disease were discovered: three of the cervix, three of the endometrium and three metastatic. There were 20 cases of carcinoma in situ and 2 of severe dysplasia. Evidence of infection was present in a high percentage of the smears. Hospital admission affords an excellent opportunity of applying this valuable screening procedure.     

Colorectal adenoma in patients with a history of breast cancer: a prospective study in Taiwan

The increased incidence of colorectal cancer in women with a history of breast cancer is well established. However, the relationship between the prevalence of adenomatous polyps and breast cancer is still controversial. We conducted a prospective study of the incidence of colorectal polyps in patients with a history of breast cancer in Taiwan. Eighty-nine patients (86 women and 3 men) received colonoscopy to test for precancerous lesions. Mean age was 49.4 +/- 10.4 years. Twelve polyps (9 adenomatous, 2 hyperplastic, 1 inflammatory) (13.5%) and one cancer (1.1%) were found. The mean age of patients with and without colorectal neoplasia was 56.3 +/- 9.4 and 48.2 +/- 10.2 years respectively, (p < 0.005); 10 out of 13 patients (77%) with colorectal neoplasia were over 50 (p < 0.1). Compared with a study of Chinese people in Hong Kong, our population had a lower incidence of colorectal adenomatous polyps, but breast cancer patients have a greater risk of developing colorectal cancer than the general population in Taiwan.     

The AutoPap system for primary screening in cervical cytology. Comparing the results of a prospective, intended-use study with routine manual practice

OBJECTIVE: To evaluate the effectiveness of the AutoPap System in detecting abnormal and normal cervical smears when used in a primary screening/quality control mode, as compared with currently established laboratory practices. STUDY DESIGN: Slides were obtained prospectively and were initially processed in the routine fashion with cytotechnologist screening followed by 10% random quality control rescreening. Slides were then processed on the AutoPap System and allocated into the following groups: (1) approximately 25% of the lowest-ranking slides were placed in the laboratory's archives as within normal limits; (2) the remaining approximately 75% of slides were subjected to manual screening. Approximately 15% of the highest-ranking slides in this group underwent quality control rescreening. For each slide needing manual screening, the cytotechnologist was supplied with a report giving the ranking score of that slide. All discrepant slides for either adequacy or diagnosis were subjected to a truth-determination process. The results obtained from the two arms of the protocol were then compared. RESULTS: The AutoPap System-assisted arm of the study was superior to the current practice arm for the identification of abnormal slides at the level of atypical squamous cells of undetermined significance and above (ASCUS+), low grade squamous intraepithelial lesion (LSIL) and higher LSIL+. AutoPap System-assisted practice was equivalent to current practice for the identification of unsatisfactory and satisfactory but limited by slides. All results showed statistical significance. In addition, AutoPap System-assisted practice in the study indicated improved specificity of diagnosis. CONCLUSION: AutoPap System-assisted practice shows superior sensitivity and specificity when compared to current practice. Its clinical use as a primary screening device should improve the overall practice of cervical cytology as well as provide potential enhancement in overall laboratory productivity.     

Detection of growth fraction in tumors by Ki67 monoclonal antibody in cytologic smears: a prospective study of 40 cases

The monoclonal antibody (MAb) Ki67 detects a nuclear antigen in cycling tumor cells. Quantitation of proliferating cells is helpful in predicting the recurrence and metastatic potential of tumors as previously reported. We conducted a prospective study on 40 benign and malignant tumors by performing Ki67 immunocytochemical stains on cytologic smears and their corresponding frozen tissues. Quantitation of Ki67 positive cells was done by counting 300 cells in 5-7 high-power fields in cytologic smears and tissues. Only nuclear or nucleolar immunostaining was considered positive for MAb Ki67. The number of Ki67 positive tumor cells in cytologic smears correlated well with Ki67 positive cells from corresponding tissues. On the average, cytologic smears showed 1.9% higher Ki67 positivity in malignant tumors as compared to their corresponding frozen tissues (P < 0.001). The Ki67 positivity in malignant tumors was found to be significantly higher when compared with benign tumors (P < 0.001). We conclude that cytologic smears can be used for the determination of growth potential in tumors by MAb Ki67. Additionally, cytologic preparations can be used during intraoperative consultations when adequate tissue is not available for the above mentioned study.     

The lower cervical spine in trauma: a study of false-negative and false-positive findings

Evaluation of roentgenographic studies of the lower cervical spine may be complicated by posttraumatic immobility, certain body types, and technical factors which produce equivocal findings. False-positive and false-negative findings are reported, with suggestions for additional views and more diagnostic evaluation.     

Natural history of sucking patterns in infant goats: A comparative study.

Examined temporal organization of sucking patterns, the phase interaction of sucking and other rhythmical motor patterns, and the effects of feeding on sucking rate in 26 Nubian goats. No changes in sucking rate were noted over the 1st 3 mo. The precise rate concordance between sucking and tail movements suggested that peripheral motor rhythms are regulated by a central sequencing mechanism which in turn is modulated by organismic and peripheral factors. A comparison of sucking patterns in 10 human infants and Ss indicates that qualitative species differences in the prefunctional organization of sucking influence the nature of the interaction between sucking performance and organismic or peripheral factors. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Natural history of innocent heart murmurs in newborn babies: controlled echocardiographic study

AIM: To define the origin and the natural history of innocent heart murmurs in newborn infants. METHODS: Fifty healthy babies born at term with the clinical diagnosis of an innocent heart murmur and 50 controls without a murmur were studied. Each baby had a complete two dimensional and pulsed Doppler echocardiogram and those with any abnormality were followed up at 6 weeks, 3 months, and 6 months until the murmur had disappeared or the heart was totally normal. Babies with congenital heart disease were excluded from the study. RESULTS: Pulmonary branch stenosis (PBS) was found in 25 (50%) of the study group and in six (12%) controls; patent ductus arteriosus (PDA) in 30 (60%) subjects and in six (12%) controls; and a patent foramen ovale (PFO) in 50 (100%) subjects and in 41 (82%) controls. At 6 weeks the murmur had disappeared in 64% of babies. PBS was still present in eight of 22 (36%) babies at 6 weeks, in 12% at 3 months, but in none at 6 months. At 6 weeks, seven of the eight with PBS still had a murmur compared with two of 14 (14%) babies in which the PBS had resolved (P < 0.005). At 6 weeks the PDA had closed in all patients but the foramen ovale was still patent in 29 of 44 (66%) subjects and nine of 33 (27%) controls. The closure of the PFO was not influenced by its size at birth. CONCLUSIONS: An innocent heart murmur in a baby born at term is often related to PBS, particularly if the murmur is still present after 24 hours of age, when most PDA have closed. At 6 weeks the murmur had disappeared and the PBS had resolved in 64% of the babies. PBS had resolved in all babies at 6 months.     

Natural history of ovarian adenocarcinomas: from epidemiology to experimentation

The ovarian carcinogenesis is not well known because the diagnosis is usually delayed to an advanced stage with a lot of chromosomic abnormalities. On the other hand, there is a lack of animal models and preneoplastic patterns are discussed. Different ways of studying are in progress. Prophylactic oophorectomy in women with BRCA1 mutation provides ovaries that can be compared to a control group. Epithelial or stromal changes are observed in the familial risk group more frequently than in the controls and could be preneoplastic. An experimental approach has been developed in order to confirm the Fathalla's theory of the incessant ovulation by culturing cells of rat surface ovarian epithelium with a high proliferative pressure. These cells become malignant in 10 out of 30 cases (after 10 cultures). The transformed tumor cells are a syngeneic tumor model that can be transplanted in the animal and analysed by molecular biology technics. This allowed to show the loss of a potentially tumor suppressor gene, lot 1, in the transformed cells and on the other hand the overexpression of a gene coding for a protease enzyme the cathepsin B, which is a marker of an aggressive metastatic power.     

Natural history of diverticular disease: when to operate?

PURPOSE: The natural history of patients admitted because of acute diverticulitis is largely unknown, and the selection of patients for surgical treatment varies notably. This study presents our experience concerning the outcome for 366 patients admitted during a 10-year period. METHODS: Three hundred sixty-six patients admitted to our hospital with acute diverticulitis from 1981 to 1990 were identified from a computer database, and their clinical data up to the end of 1996 were reviewed from the database and patient records. RESULTS: There were significantly more males than females in the age group less than 50 years old, and young males underwent surgical treatment during the first treatment period more frequently than the others. Young patients were operated on without mortality, and all their temporary colostomies were closed. Older patients died more often of diseases unrelated to the diverticular disease during the years after the first episode of acute diverticulitis. Recurrences of diverticular disease developed in 22 percent of patients, and they were significantly more common in patients less than 50 years old than in the older age groups. Males less than 50 years old more often developed complications of diverticular disease after two hospital admissions. CONCLUSIONS: Males first admitted when less than 50 years of age undergo more primary operations and develop more recurrences of diverticular disease than do older people. Based on our data, however, we recommend surgery for all patients after two episodes of acute diverticulitis that resolves after conservative treatment with antibiotics.     

Computer-assisted primary screening of cervical smears using the PAPNET method: comparison with conventional screening and evaluation of the role of the cytologist

The reactions of 221 women to their place of delivery (state or private hospital), type of delivery (vaginal or Caesarean) and associated obstetrical interventions were explored by means of a structured interview conducted at 3 months postpartum. Women were randomly selected from the birth records of three cultural groups residing in the municiple area of Johannesburg, South Africa: White (n = 72), Indian (n = 79) and Mixed cultural origin (n = 78). The type of birth experienced by women differed in the cultural groups examined. While most women experienced positive emotional reactions to birth many also expressed a variety of negative reactions. The differences in care experienced by women in the present study reflect the impact of the two systems of care, private and state, that are available to women in South Africa.     

Multiparameter flow cytometric DNA analysis of effusions: a prospective study of 36 cases compared with routine cytology and immunohistochemistry

Single-parameter flow cytometry (SFCM) is limited in its ability to detect aneuploid and diploid malignant cells or accurately estimate S-phase fractions (SPF) in effusions because of the high degree of contamination by benign mesothelial cells and inflammatory cells. We examined 36 pleural and peritoneal fluids by conventional cytology and multiparameter FCM (MFCM) to analyze the DNA content of cells expressing epithelial markers cytokeratin, epithelial membrane antigen, carcinoembryonic antigen, BRST-1, or BRST-3 (B72.3) and compared the results to those found with SCFM. The cases were also studied by immunohistochemistry using the same antibody panel. By routine cytology, 14 of the 36 cases were classified as carcinomas, 11 as reactive, 1 as mesothelioma, and 10 as suspicious. MFCM allowed reclassification of 5 of the 10 suspicious cases as carcinomas and the remaining 5 as reactive cases based on ploidy and marker expression. Whereas SFCM detected only 13 nondiploid carcinomas, MFCM detected 4 diploid and 15 nondiploid carcinomas. All reactive cases were diploid by SFCM or MFCM. The mesothelioma case showed were distinct peaks by MFCM, a diploid peak with SPF of 13.4% and a tetraploid peak with SPF of 36.1%. The SPF of the nondiploid carcinomas ranged from 5.9 to 50.4% and diploid carcinomas, from 3.5 to 14.5% when gated on epithelial cells. The reactive cases had SPF ranging from 0.4 to 4.4%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impact of prenatal mid-trimester screening on the prevalence of fetal structural anomalies: a prospective epidemiological study

The objective of this study was to evaluate the effectiveness of the measurement of maternal serum alpha-fetoprotein (MSAFP) at 16 weeks and a subsequent routine ultrasound screening at 18-20 weeks' gestation and the impact on the birth prevalence of congenital structural anomalies in an unselected pregnant population of Hungary in a prospective epidemiological study. A total of 63,794 pregnant women (representing one-sixth of the population of Hungary) were offered this screening program over 3 years (1988-90). Of the pregnant population, 75.7% (48,312) received MSAFP screening and in 81.0% (51,675), at least one ultrasound scan was performed. In the screened pregnancies, 496 craniospinal, thoraco-abdominal, urogenital and other severe major anomalies occurred; 317 were detected at 18-20 weeks (sensitivity 63.1%; specificity 100.0%; positive predictive value 100.0%). The sensitivity of ultrasound scanning was significantly higher (p < 0.05) than that of the MSAFP screening. (At the time of ultrasound scanning the MSAFP value was known.) In this study, the less serious anomalies such as hydrocele, hypospadias and undescended testicle were not systematically searched for, but the birth prevalences were calculated. The overall mid-trimester prevalence of severe plus less severe major anomalies was 2.26%. The birth prevalences of severe major anomalies were 0.57 (craniospinal), 4.36 (thoracoabdominal and urogenital) and 1.21 (other severe) per 1000. These values were lower than the mid-trimester prevalences which were 2.94, 5.20 and 2.06 per 1000, respectively. The prevalence values at the age of 1 year were also calculated (0.36, 2.21, 0.54 per 1000, respectively). We conclude that our screening program with availability of termination of pregnancy could significantly (p < 0.05) reduce the prevalence of severe major abnormalities at birth. Training programs in cardiac scanning are required.     

Value of endobiliary brush cytology and biopsies for the diagnosis of malignant bile duct stenosis: results of a prospective study

BACKGROUND: Before considering a nonsurgical method of management of a bile duct stenosis, a tissue diagnosis is highly desirable. In a prospective study we have evaluated the feasibility and reliability of endobiliary brush cytology and biopsies performed at the time of endoscopic retrograde cholangiography. METHODS: Two hundred thirty-three consecutive patients underwent an attempt at endobiliary brush cytology and biopsies of bile duct stenosis when no mass was detected on ultrasound and CT scan. RESULTS: The material for cytology was sufficient for analysis in 210 cases (90%) and biopsies were obtained in 128 cases (55%). One hundred fifteen patients had both cytology and biopsies (49%). For the diagnosis of malignant stenosis, the sensitivity was 35% for cytology, 43% for biopsies, and 63% for the combination of cytology and biopsies. For both cytology and biopsies, the specificity was 97%. In the cases of cancer primarily involving the bile ducts, the sensitivity was 86% when combining both cytology and biopsies. CONCLUSIONS: Endobiliary sampling is technically difficult and has a limited sensitivity for the diagnosis of malignant biliary stenosis. Biopsies should be combined with cytology to increase the sensitivity.     

Multicystic kidney dysplasia: a prospective study on the natural history of the affected and the contralateral kidney

In a 6-year period, 41 young infants with multicystic kidney dysplasia were seen in our department. In 30 cases, the diagnosis had already been suspected by prenatal ultrasonography. A prospective protocol was proposed to the parents which comprised ultrasound evaluation every 3 months until the age of 24 months and renal function assessment at the age of 18 months. In 33 patients, the study was completed as scheduled. At the start of the study, the maximal diameter of the multicystic kidney was above the mean length of normal kidneys in all cases where precise measurement was possible. Within 24 months, 7 of the dysplastic kidneys disappeared, 20 regressed in size, 1 remained unchanged and only 5 increased in size. Between the age of 0 to 3 months, renal length of the contralateral kidney was within the normal range in 19 infants and above +2SD in 14 cases. At the age of 18 to 24 months, renal length was, with few exceptions, between 0 and +4SD. Inulin clearance was normal in all 33 individuals with a median value of 112 ml/min per 1.73 m2. CONCLUSION: As a rule, multicystic kidneys shrink in the first 2 years of life. In most cases the contralateral kidney maintains a normal renal function as a consequence of progressive compensatory hypertrophy.     

Natural history of low back pain. A longitudinal study in nurses

STUDY DESIGN: Longitudinal study. OBJECTIVES: To assess the natural history of low back pain. SUMMARY OF BACKGROUND DATA: Most episodes of low back pain resolve or improve within a few weeks, but chronic or recurrent symptoms are common. Previous studies of natural history have usually relied on people's long-term recall of symptoms, or they have been limited to patients seeking clinical care. METHODS: Nurses (1,165 women) completed a baseline questionnaire and up to eight follow-up questionnaires 3 months apart. Each questionnaire asked whether they had experienced low back pain in the past month. One-month prevalences of pain at specified follow-ups were calculated according to histories of pain reported on earlier questionnaires. RESULTS: The 1-month prevalence of low back pain at individual follow-ups ranged from 16% to 19%. Of 906 women who completed the baseline questionnaire and at least three follow-up questionnaires, 38 (4.2%) reported pain every time they returned a questionnaire, and 190 (21.0%) reported pain on at least three occasions. The presence or absence of low back pain at baseline was highly predictive of future pain throughout follow-up. The longer that back pain was consistently reported, the more likely it was to be present at the next follow-up. Later risk was lowest in women who reported no back pain at baseline or either of the first two follow-ups. Back pain carried a worse prognosis if it was disabling or associated with sciatica. CONCLUSIONS: Our results confirm the importance of back pain duration and the occurrence of associated disability and sciatica as predictors of future symptoms, and allow more reliable quantification of the natural history of back pain in women of working age. In the absence of other information, the differentials in risk associated with a person's history of back pain appear to remain constant for a period of at least 2 years.     

Respiratory allergy in laboratory animal workers: a retrospective cohort study using pre-employment screening data

OBJECTIVES: To study the role of exposure, atopy, and smoking in the development of laboratory animal allergy (LAA) in a retrospective cohort study. METHODS: Between 1977 and 1993, 225 people received a pre-employment screening when they started a job at a Dutch research institute where they were going to work with laboratory animals. After active follow up 136 of them (60.4%) could be traced and were sent a questionnaire with extensive questions on allergic symptoms, smoking habits, and job history. 122 people (89.7%) sent back a completed questionnaire. Those who were accepted for a job at the institute and did not have allergic symptoms at the start of the job were selected as cohort members. After selecting people with complete data on start and end date of jobs, exposure intensity, atopy, and smoking, the cohort consisted of 99 people with an average time of follow up of 9.7 years. LAA was defined as a positive response to a set of questions in the questionnaire. The mean number of hours a week a person was exposed to laboratory animals at entry of the cohort was used as a surrogate for exposure, and was divided into four categories. RESULTS: 19 cohort members (19.2%) reported LAA. More people with asthmatic symptoms were found in the high exposure categories. More atopic than non-atopic people reported asthmatic symptoms (13% v 6%). The mean time until development of symptoms of LAA was about 109 months in non-atopic people (n = 9), and 45 months in atopic people (n = 10) (t test; P < 0.05). Time until development of symptoms of LAA was shorter at a higher intensity of exposure, except for those exposed for less than two hours a week. A proportional hazard regression analysis showed that exposure and atopy were significant determinants of LAA. An increased relative risk (RR) was found for non-atopic people exposed to laboratory animal allergens for more than two hours a week. Atopic people had an even higher risk when exposed to laboratory animals for more than two hours a week (RR above 7.3). Sex, smoking, and age were not risk factors. More atopic than non-atopic people were absent from work or transferred because of allergies. CONCLUSIONS: This study showed that exposure and atopy are significant predictors of LAA and that the risk of developing LAA remained present for a much longer period (> 3 y) than considered before.