Coalescence of liquid drops by surface tension.

The merging of two mercury drops at very low kinetic energy is observed using fast, digital, and analog imaging techniques. Sequences showing the time evolution of the overall-surface shape as well as an amplified view of the contact region are shown. Qualitative and quantitative comparisons with computations of the Navier-Stokes equation with a free surface are made. In the model, the surface is tracked by a marker-chain method.

Prognostic significance of DNA cytometry of postirradiation cervicovaginal smears.

BACKGROUND: Cytologic sampling is performed routinely after radiotherapy for cervical carcinoma. The prognostic significance of postirradiation dysplastic and atypical cells is uncertain because of difficulties in distinguishing preneoplastic and cancerous changes from benign radiation changes. DNA cytometry studies may provide a more objective method of identifying significant lesions. METHODS: Postirradiation cervical carcinoma patients with cervical/vaginal smears containing atypical or dysplastic cells were identified prospectively. Papanicolaou smears were destained, restained with a Feulgen stain, and evaluated for DNA content using image cytometry. Pathologic and clinical records were monitored on each patient for evidence of recurrence or biopsy-proven dysplasia. RESULTS: Of 46 patients, 14 had been diagnosed on cytology as having atypical squamous cells, 4 as having atypical/suspicious cells, 12 with low grade squamous intraepithelial lesions (SIL), 3 with high grade SIL, and 13 with ungraded SIL. DNA histograms were classified as follows: 14 diploid, 19 polyploid, and 13 aneuploid. Cytologic diagnosis and histogram type were correlated significantly and both correlated with clinical outcome. The probability of either postirradiation dysplasia or recurrence was as follows: SIL, 82%; suspicious, 100%; polyploid, 79%; and aneuploid, 92%. Patients with atypical squamous cells of undetermined significance or diploidy most frequently had negative follow-up (57% each). All patients with both SIL and aneuploidy developed either dysplasia or recurrence. The stage of disease did not correlate with outcome or histogram pattern. CONCLUSIONS: DNA analysis of postirradiation cytologic smears demonstrating atypia or dysplasia may provide useful ancillary information. The presence of aneuploidy usually signifies either recurrence or dysplasia. Polyploidy most frequently occurs in dysplastic processes, whereas diploid histograms usually denote a benign disease course.

Evaluation of PAPNET testing as an ancillary tool to clarify the status of the "atypical" cervical smear.

To assess the utility of the PAPNET system (Neuromedical Systems Inc., Suffern, NY) in clarifying the status of cervical smears showing borderline abnormalities, we analyzed the results of five cytotechnologists who reclassified 200 "atypical" smears by evaluating PAPNET images only. The interobserver agreement (reliability) of the PAPNET reviewers was computed, and their readings were compared with three standards: the consensus diagnosis of five pathologists who used light microscopy, the detection of cancer-associated human papillomavirus DNA by Southern analysis, and the correlation with diagnoses of biopsy specimens obtained during passive follow-up. The PAPNET reviewers classified 18 to 65% of cases as normal, 25 to 42% as equivocal, and 10 to 55% as abnormal. Unanimous interobserver agreement was achieved in only 24 (13%) cases. Four of the five PAPNET reviewers agreed moderately well with the results of the pathology reference panel. In four of the five PAPNET reviews, classification of cases as abnormal was strongly correlated with the detection of cancer-associated types of human papillomavirus. Consensus PAPNET results of abnormal were predictive of abnormal histologic findings at follow-up. Theoretically, if colposcopy had been performed on all of the women with equivocal or abnormal PAPNET results (based on the consensus of the panel), as much as 95% of biopsy-confirmed lesions could have been detected, but 79% of women would have been referred. Restriction of colposcopy referral to women with definitely abnormal PAPNET readings would have reduced referrals to 31%, but the sensitivity of the triage would have dropped to 51% of biopsy-confirmed lesions.

Clinicopathologic correlation of the unsatisfactory Papanicolaou smear.

BACKGROUND: The 1991 Bethesda System for cervical/vaginal cytology reporting defined adequacy criteria for the unsatisfactory designation. Most laboratories have implemented these criteria, but clinical implications have not been established. METHODS: Researchers at two university hospitals retrieved by computer search all unsatisfactory Papanicolaou (Pap) smears taken between January 1994 and July 1995. Of 71,872 total Pap smears, 208 (0.3%) were unsatisfactory (corresponding atypical rate of 9% and a dysplasia/carcinoma rate of 6.5%). Time interval to follow-up and clinicopathologic outcome were determined. RESULTS: Approximately 26% of unsatisfactory Pap smears were from patients with a history of epithelial abnormalities. The majority (129 of 208 specimens; 62%) of follow-up Pap smears or biopsies occurred within 6 months, 5.7% within 6-12 months, and 1.4% in 12-18 months. Approximately 31% had no follow-up. The first repeat Pap smear or histologic specimen in 144 patients with follow-up was negative in 107 (74%), unsatisfactory in 6 (4%), atypical squamous cells of undetermined significance in 15 (10%), squamous intraepithelial lesion (SIL) in 13 (9%), and malignant in 3 (2%). Nonmalignant conditions contributing to the unsatisfactory smears on histologic specimens (12%) included cervicitis, endometritis, endometrial hyperplasia, and polyps. Progressive abnormalities after the first repeat specimen were noted in 7 patients (5%). A total of 23 of 144 initial unsatisfactory specimens (16% )were found to be from patients diagnosed with SIL or malignancy when all follow-up specimens were analyzed. CONCLUSIONS: The majority of patients with unsatisfactory Pap smears had follow-up studies within 6 months. A significant number (16%) of those with follow-up had eventual diagnoses of SIL or neoplasia. Benign pathologic conditions also contributed to unsatisfactory smears. This patient subset was more likely to have a history of abnormalities, confirming the importance of peer/hierarchical review of unsatisfactory smears.

A cost analysis of the prevention of end-stage renal disease: immunoglobulin therapy for IgA nephropathy.

A cost analysis was used to evaluate three possible immunoglobulin (IgG) treatment protocols for end-stage renal disease due to IgA nephropathy. The perspective chosen for the cost analysis was that of the health-care delivery system. The baseline strategy was the absence of IgG treatment, and alternative strategies corresponded to three protocols presently on trial: all three included a high initial dose of intravenous IgG. Protocol 1 followed with intramuscular IgG injections only, protocol 2 with intramuscular plus intravenous injections, and protocol 3 with intravenous injections only. The costs of treatment included the costs of immunoglobulins, outpatient hospital costs, and the costs of tests; the saving (costs averted) resulted from kidney dialysis averted. The bottom line for the health-care system is a net savings of $233,000, $213,000, or $83,000, depending on the protocol chosen. The computation of costs did not value physical and psychological health benefits. Thus, any subjective benefit, such as improved comfort, or objective benefit, such as longer life expectancy, would be an improvement over the results presented here.

Efficacy of automated cervical cytology screening.

The Papanicolaou stained cervicovaginal smear (Pap smear) is a gynecologic cytologic screening tool that has dramatically reduced the incidence and mortality of cervical cancer. Recently, a number of problems with the Pap smear test, including severe cytotechnologist shortages, lack of internal quality controls, and high false negative rates have been emphasized by the scientific community and the general public. To address some of these problems, there has been increased development of a number of automated and semiautomated cytologic screening systems. A semiautomated screening system (PAPNET) was used to retrospectively evaluate 527 conventionally prepared Pap smears from 500 consecutive unselected patients. This system scanned the slides and displayed 128 of the most "abnormal" areas of each slide on a monitor. A screener reviewed these "abnormal" images in a blinded fashion and decided whether they represented variants of normal cytology, were inadequate for evaluation, or were abnormal and warranted manual review of the material. The screener's evaluations were then compared to the previously made diagnosis and discrepancies were reviewed. After review of the images from 500 patients, 343 (69%) were deemed to be normal cytology, 140 (28%) were abnormal and needed manual review, and 17 (3%) were inadequate. Of the 343 called normal using this system, 338 were previously called normal and five patients were previously diagnosed with either atypical squamous cells of undetermined significance (ASQUS) or low grade squamous intraepithelial lesions (LGSIL). Of the 140 thought to need review, 43 were previously diagnosed with squamous or glandular disease and 97 were previously diagnosed as normal. Slides from the apparent false negatives and false positives were again reviewed in a blinded fashion.(ABSTRACT TRUNCATED AT 250 WORDS)

DEALE-ing and discounting: a simple way to compute the accrued costs of preventive strategies.

Researchers agree on the importance of discounting costs and of including mortality rates in the cost computations. The authors present a simplified mathematical model that allows both DEALE-ing and discounting and permits easy computations of accrued and incremental costs. The general formula of the accrued discounted cost of treating over time of life expectancy is: C = Co/mu asr + mu D + i A systematic discussion of the errors involved in the DEALE approximation shows that it will in most cases truly describe the ordering of the costs of various treatments. The DEALE are compared with the costs obtained by using actual mortality statistics. It was found that when two strategies have actual costs CA and CB such as CA greater than CB and CA/CB superior to 1.25, the ordering of CA and CB will always be kept in this simplified model.

Laboratory compliance with federal government and professional society recommendations.

Quality assurance issues have assumed growing importance in the cytology laboratory. The 1988 Clinical Laboratories Improvement Amendment (CLIA '88) (United States Department of Health and Human Services, Federal Register: U.S. Government Printing Office 1990;55:9495) regulates the patient identifiers and clinical data on the requisition form but does not mandate physician compliance to provide the information. We investigated the use of patient identifiers and clinical data by laboratories as specimen acceptance/rejection criteria. We surveyed 81 board certified cytopathologists and 235 randomly selected cytology laboratories for acceptance criteria of cytology specimens and received responses from 104. Approximately two thirds of all responding laboratories had specific criteria for rejecting specimens on the basis of inadequate identification or clinical data. While the vast majority required the specimens to be identified with patient name, collection date, and specimen source, a minority of laboratories required clinical information such as LMP, prior atypical cytologic/histologic specimens, and history of previous therapy. Little correlation was found between practice setting and the use of rejection criteria.

Cytomegalovirus sialadenitis in patients with the acquired immunodeficiency syndrome: a potential diagnostic pitfall with fine-needle aspiration cytology.

We report three cases of cytomegalovirus (CMV) sialadenitis which presented as parotid gland nodules in patients infected with the human immunodeficiency virus. While CMV is known to widely infect patients with the acquired immunodeficiency syndrome (AIDS), we are aware of only a single report of CMV sialadenitis in a patient with AIDS (Pialoux et al.: Rev Infect Dis 1991;13:338). Utilizing fine-needle aspiration (FNA) cytology as the initial investigative modality, two cases were correctly diagnosed preoperatively while the third case displayed atypical features and was interpreted erroneously as carcinoma leading to surgical intervention. Upon review of these cases of CMV sialadenitis, the characteristic intranuclear inclusions are best identified with Papanicolaou (Pap) staining. CMV sialadenitis should be considered in the differential diagnosis of painless salivary gland enlargement in patients with AIDS. We believe this lesion can be diagnosed preoperatively with FNA and the interpretation is aided by evaluating both Pap- and Giemsa-stained material.

Review of negative Papanicolaou tests. Is the retrospective 5-year review necessary?

New federal regulations require review of all available negative gynecologic smears within the previous 5 years for each patient with a current high grade squamous intraepithelial lesion (HGSIL) or above. Two university hospitals retrospectively reviewed all patients who had HGSIL or above and who had prior negative smears. During 18 months, 35,807 Papanicolaou tests were reported, from which we identified 44 patients with 80 negative smears before presenting with HGSIL or above. These 80 negative smears were rescreened and, on review, there was agreement with the original diagnosis in 66 cases (82.5%). Fourteen (17.5%) smears were reclassified: 2 unsatisfactory, 6 atypical squamous/glandular cells of undetermined significance, 3 low grade SIL, and 3 HGSIL or above. Of the 12 cases satisfactory for reclassification, 9 (75%) occurred within 2 years before the HGSIL or above. Two cases of atypical squamous/glandular cells occurred within 4 years. One case of HGSIL occurred more than 4 years before, but a negative Pap smear had been reclassified within the year before the diagnosis of HGSIL. The authors conclude that a 2-year retrospective review, which identified 75% of our false-negative cases, is an effective and efficient quality control and assurance practice.

Diagnostic accuracy and clinical utility of fine-needle aspiration cytology in the diagnosis of clinically primary bone lesions.

Optimal treatment of primary bone sarcomas requires minimal disturbance of the tumor prior to preoperative radiation and chemotherapy. Currently, carefully planned incisional or cutting needle biopsies are the favored methods for procurement of specimens. Recently, fine-needle aspiration has gained favor as the initial diagnostic procedure at some centers. We investigated the diagnostic accuracy and the effects of errors in diagnosis and of complications on the patient's course in a series of 101 patients presenting with lesions clinically believed to have arisen in bone. We found that 29% of aspirates were insufficient for the diagnosis; 41% of aspirates yielded a correct diagnosis that had a significant favorable impact on the patient's course, while 20% of aspirates gave a correct diagnosis that did not significantly influence therapy. In 7% of cases, the aspirates were associated with an incorrect diagnosis that negatively influenced therapy, and in an additional 3% of cases an incorrect diagnosis was obtained that had no impact on patient outcome. No complications were encountered in this series of patients.

Problems encountered with the Bethesda System: the University of Iowa experience.

This paper provides a descriptive summary of 1 year's experience with the Bethesda Cytologic Classification System at the University of Iowa Hospitals and Clinics. Cytotechnologists and pathologists criticized the failure of the new classification system to provide microscopic criteria for the following categories: adequacy of the smear (satisfactory, less than optimal, unsatisfactory), atypical squamous cells of undetermined significance, atypical glandular cells of undetermined significance, and inflammation-associated changes. Clinicians criticized the "less than optimal" category and the reporting of koilocytosis, moderate dysplasia, and endometrial cells. Suggestions for modifying the Bethesda System include: eliminating the less than optimal response, defining what constitutes an unsatisfactory smear, eliminating the terms low-grade and high-grade squamous intraepithelial lesion, and changing the reporting of endometrial cells.

The association between pregnancy and human papilloma virus prevalence.

This study examined the effects of pregnancy on the prevalence of HPV infection, comparing 69 pregnant and 54 nonpregnant age-frequency matched female patients. HPV prevalence was detected by DNA hybridization using the ViraPap/ViraType dot blot procedure. The prevalence of HPV among pregnant women increased with gestational age from 8.0% in the first trimester, to 16.7% in the second, and 23.1% in the third trimester. This finding suggests that HPV infection may be activated by hormonal or other effects of pregnancy and may explain why number of pregnancies is known to be associated with increased risk of cervical dysplasia and cancer. Oncogenic HPV types 16/18 and 31/33/35 were identified with almost equal frequency in the study population whereas HPV 6/11 was seen rarely. The logistic regression models indicate that there were no significant differences between HPV positive and HPV negative groups by age, income, number of sex partners, age of first intercourse, average frequency of intercourse per month, number of pregnancies, oral contraceptive duration, or pregnancy status. There were no interaction effects. A current Pap result of cervical dysplasia (OR = 8.9; 95% confidence interval: 2.1, 38.8), oral contraceptive use (OR = 0.1; 0.03, 0.6), and education (OR = 1.4; 1.1, 1.8) were significant predictors of HPV status.

PIP: Between October 1987-May 1988, researchers compared 69 pregnant patients with 54 age matched nonpregnant patients at the University of Iowa Medical School Hospital in Iowa City to examine the effects of pregnancy on the prevalence of human papilloma virus (HPV) infection. Almost all cases and controls were White. Pregnant women had more risks for cervical dysplasia and cancer than nonpregnant women: a simultaneous diagnosis of dysplasia/squamous intraepithelial lesions [odds ration(OR) 7.4], current and past smoking (p.001 and p.05), greater number of partners (p.05) and pregnancies (p(.001), an earlier age at 1st intercourse (p.001), a higher frequency of intercourse/month, less education (OR 1.4), and poorer. In addition, pregnant women tended not to use condoms (p.01) which can prevent transmission of sexually transmitted diseases. Oral contraceptive (OC) use had a protective effect (OR 0.1), but duration of OC use did not significantly change the ORs. The 2 groups had basically the same overall frequency of HPV (15.9% pregnant and 14.8% nonpregnant), but HPV frequency increased as did gestational age. For example, it was 8% for the 1st trimester, 16.7% for the 2nd trimester, and 23.1% for the 3rd trimester. This increase in frequency suggested that it occurs with activation of latent HPV infection or increased HPV plasmid replication during pregnancy. The researchers hypothesized that high progesterone levels may activate transcriptional HPV replication or change an immune response. Other studies demonstrated that increasing parity is linked with cervical cancer. Thus the researchers proposed that other researchers to set up longitudinal studies to follow pregnant and postpartum women to see if condylomas, cervical dysplasia, and cancer subsequently develop. These studies will allow researchers to determine if HPV status during the 2nd and 3rd trimesters predicts disease.