Parallels in the epidemiology of selected anogenital carcinomas.

Characteristics of Los Angeles, Calif., residents in whom carcinomas of the cervix, vulva, vagina, anus, and penis were diagnosed during the period 1972-81 were compared with those of all residents and with those in whom any cancer was diagnosed during the same period. At all five sites, risks for squamous and transitional cell carcinomas generally increased with decreasing social class, were low among Jews (not explained by social class), and were elevated among persons who were separated or divorced at diagnosis compared to married persons. Single men had a striking excess of anal but not penile carcinomas. The five sites represent contiguous and histologically similar tissues, and the clinical literature suggests common risk factors, e.g., sexually transmitted infections and other forms of chronic irritation. These observations are all consistent with the hypothesis that tumors at these sites have common or similar etiologic elements.

Risk factors for invasive cervical cancer among Latinas and non-Latinas in Los Angeles County.

A case-control study among white women in Los Angeles County was conducted to investigate etiologic factors that might explain the high rates of invasive cervical cancer among Latinas. Two hundred patients with invasive squamous cell carcinoma of the uterine cervix and matched (age, sex, preferred language, and neighborhood) controls were interviewed, 98 pairs in English and 102 pairs in Spanish. Seven factors were found to contribute independently and significantly (P less than .01) to risk, each after adjustment for the other six: years since last Pap smear, years of education (protective), frequency-years douching, pack-years of smoking, years of barrier contraceptive use (protective), number of sexual partners before age 20, and recognized episodes of genital warts. An eighth variable, interval in years between menarche and first intercourse, was the second variable to enter the stepwise logistic regression analysis but lost its statistical significance when sexual partners before age 20 entered the model. Together, these eight variables accounted for almost 99% of the risk. There were no significant interactions between any of these variables and age, language of interview, or birth in a Latin country. There was no increased risk associated with use of oral contraceptives, either before or after adjustment for the other significant factors. Compared to English-speaking controls, Spanish-speaking controls smoked less, douched less, had fewer sexual partners before 20, and had essentially the same average interval between menarche and first intercourse and the same average number of episodes of genital warts; however, they had had a longer interval since their last Pap smear, fewer years of barrier contraceptive use, and fewer years of education. Education, presumably a correlate of an inadequately measured etiologic risk factor (possibly papillomavirus infection), was responsible for the greatest difference in risk between the Spanish- and English-speaking cases.

Increased frequency of adenocarcinoma of the uterine cervix in young women in Los Angeles County.

By hypothesizing that oral contraceptives (OC's) might have a carcinogenic effect on glandular cells of the cervix if given during periods of active metaplasia (e.g., postmenarchal adolescence), an increasing rate of cervical adenocarcinoma was predicted in young women who had been teenagers when OC's were introduced roughly 20 years ago. Secular trends for cervical carcinomas in non-Hispanic whites were examined by age, histologic type, and social class by using data from the Los Angeles County population-based tumor registry. Between 1972 and 1982, the frequency of invasive cervical adenocarcinoma in women under 35 years of age increased from about 2 to about 5 annually, amounting to an average rate of change of 8% per year (P less than .01). There was essentially no trend for women over 35 years old; the frequency of other invasive carcinomas (and of squamous carcinoma in situ) decreased at average rates of about 3% per year in women under 35 years of age and decreased more rapidly in older women. The increase in adenocarcinoma, unlike risk from cervical cancer generally, was most striking among young women residing in middle-to-upper income neighborhoods, who were the first to use OC's; in this subgroup the average rate of increase was 16% per year (P less than .05). These findings are compatible with our hypothesis and merit further study.

Estrogen-progestin replacement therapy and endometrial cancer.

BACKGROUND: It has been known for more than 20 years that estrogen replacement therapy substantially increases a woman's risk of developing endometrial cancer. To reduce this increased risk, progestins have been added to estrogen replacement therapy for between 5 and 15 days (usually 7 or 10 days) per "month" in a sequential fashion (sequential estrogen-progestin replacement therapy) or with each dose of estrogen replacement therapy (continuous combined replacement therapy). At the present time, however, little is known about the effects of varying the number of days that progestin is used in sequential estrogen-progestin replacement therapy. PURPOSE: We sought to determine the effects of sequential estrogen-progestin replacement therapy and continuous combined replacement therapy on a woman's risk of developing endometrial cancer. METHODS: A population-based, case-control study of 833 case subjects and 791 control subjects was conducted. Women were postmenopausal, white, and aged 50-74 years when first diagnosed with invasive endometrial cancer or were aged 50-74 years at the matching date for control subjects. All subjects were interviewed in person with the aid of a month-by-month calendar. Relative risks were estimated by odds ratios (ORs); ORs were adjusted simultaneously for the different forms of hormone replacement therapy and for the known endometrial cancer risk factors. RESULTS: The adjusted OR was 2.17 (95% confidence interval [CI] = 1.91-2.47) per 5 years of estrogen replacement therapy use (based on 422 users among the case subjects and 262 users among the control subjects). For women who received sequential estrogen-progestin replacement therapy with the progestin given for less than 10 days (effectively 7 days) per month, the adjusted OR was only slightly reduced to 1.87 (95% CI = 1.32-2.65) per 5 years of use (74 case subjects and 47 control subjects). However, when progestin was given for 10 or more days (effectively 10 days), there was essentially no increased risk (adjusted OR = 1.07 per 5 years of use; 95% CI = 0.82-1.41) (79 case subjects and 88 control subjects). Continuous combined replacement therapy was also associated with essentially no increased risk (adjusted OR = 1.07 per 5 years of use; 95% CI = 0.80-1.43) (94 case subjects and 81 control subjects). CONCLUSIONS: The progestin in sequential estrogen-progestin replacement therapy needs to be given for at least 10 days to block effectively any increased risk of endometrial cancer. Continuous combined estrogen-progestin therapy is similarly effective. Neither regimen reduces a woman's underlying risk of endometrial cancer. The sharp distinction between the effects of less than 10 days (effectively 7 days) and 10 or more days (effectively 10 days) of progestin use in sequential estrogen-progestin replacement therapy suggests that the extent of endometrial sloughing may play a critical role in determining endometrial cancer risk.

A case-control study of occupational and dietary factors in colorectal cancer in young men by subsite.

With the hope that exposures responsible for colorectal cancer might be especially obvious among those in whom it develops early, 147 men with colorectal carcinomas first diagnosed between the ages of 25 and 44 years were compared to neighborhood controls. Physical activity on the job was protective for tumors located in the transverse and descending portions of the colon. Rectal cancer and to a lesser extent sigmoid cancers were associated with jobs in which dusts or fumes were inhaled, especially if those jobs were held for long periods in young adulthood. While risk for rectal cancer did not seem to be limited to any particular type of dust or fume, the excess risk was strongest for wood and metal dusts. Consumption of fruits and vegetables and a preference for whole grain breads were protective for colon but not rectal cancers, while consumption of deep fried foods and barbecued/smoked meats increased risk at specific subsites. Beef intake, alcohol consumption, and cigarette smoking appeared to play little or no role at any subsite.

Predicting future diabetes in Latino women with gestational diabetes. Utility of early postpartum glucose tolerance testing.

We tested 32 routine clinical parameters for their ability to discriminate between a high risk and a low risk of non-insulin-dependent diabetes mellitus (NIDDM) within 5-7 years after pregnancies complicated by gestational diabetes mellitus (GDM). Latino women (n = 671) with GDM who did not have diabetes 4-16 weeks after delivery returned for at least one 75-g oral glucose tolerance test (OGTT) within 7.5 years. Multivariate analysis was used to identify parameters ascertained during or immediately after the index pregnancy that were independently associated with the development of diabetes during follow-up. Life table analysis revealed a 47% cumulative incidence rate of NIDDM 5 years after delivery for this cohort of patients who did not have diabetes at the initial postpartum examination. Four variables were identified as independent predictors of NIDDM: the area under the OGTT glucose curve at 4-16 weeks postpartum, the gestational age at the time of diagnosis of GDM, the area under the OGTT glucose curve during pregnancy, and the highest fasting serum glucose concentration during pregnancy. Examination of relative risks (RRs) of NIDDM between the highest and lowest quartiles of the cohort for each variable, adjusted for the other three variables, revealed that the postpartum OGTT provided the best discrimination between high-risk and low-risk individuals (adjusted RR = 11.5 [95% confidence interval 4.5-29.1] compared with adjusted RRs of only 0.5-2.5 for the other three variables).(ABSTRACT TRUNCATED AT 250 WORDS)

Multiple metabolic defects during late pregnancy in women at high risk for type 2 diabetes.

Detailed metabolic studies were carried out to compare major regulatory steps in glucose metabolism in vivo between 25 normal pregnant Latino women without and 150 pregnant Latino women with gestational diabetes mellitus (GDM). The two groups were frequency-matched for age, BMI, and gestational age at testing in the third trimester. After an overnight fast, women with GDM had higher fasting plasma glucose (P = 0.0001) and immunoreactive insulin (P = 0.0003) concentrations and higher glucose production rates (P = 0.01) but lower glucose clearance rates (P = 0.001) compared with normal pregnant women. During steady-state hyperinsulinemia (approximately 600 pmol/l) and euglycemia (approximately 4.9 mmol/l), women with GDM had lower glucose clearance rates (P = 0.0001) but higher glucose production rates (P = 0.0001) and plasma free fatty acid (FFA) concentrations (P = 0.0002) than the normal women. These intergroup differences persisted when a subgroup of 116 women with GDM who were not diabetic < or = 6 months after pregnancy were used in the analysis. When all subjects were considered, there was a very close correlation between glucose production rates and plasma FFA concentrations throughout the glucose clamps in control (r = 0.996) and GDM (r = 0.995) groups. Slopes and intercepts of the relationships were nearly identical, suggesting that blunted suppression of FFA concentrations contributed to blunted suppression of glucose production in the GDM group. In addition to these defects in insulin action, women with GDM had a 67% impairment of pancreatic beta-cell compensation for insulin resistance compared with normal pregnant women. These results demonstrate that women with GDM have multiple defects in insulin action together with impaired compensation for insulin resistance. Our findings suggest that defects in the regulation of glucose clearance, glucose production, and plasma FFA concentrations, together with defects in pancreatic beta-cell function, precede the development of type 2 diabetes in these high-risk women.

Antepartum predictors of the development of type 2 diabetes in Latino women 11-26 months after pregnancies complicated by gestational diabetes.

In this study, we sought to identify antepartum characteristics that predict the de novo development of diabetes 11-26 months after the index pregnancy in a carefully characterized cohort of women with gestational diabetes mellitus (GDM). Oral and frequently sampled intravenous glucose tolerance tests (OGTTs and FSIGTs), hyperinsulinemic-euglycemic clamps with labeled glucose, and body composition studies were performed on 91 islet cell antibody-negative Latino women with GDM during the third trimester of pregnancy. The women were documented to be diabetes-free within 6 months postpartum. Their diabetes status was ascertained again between 11 and 26 months postpartum. Logistic regression analysis was used to identify independent predictors of the development of diabetes within that interval. Fourteen of the women developed diabetes by World Health Organization criteria 11-26 months after delivery of the index pregnancy. Three antepartum variables were independent predictors of diabetes: the 1-h postchallenge plasma glucose concentration from the 100-g OGTT at which GDM was diagnosed (higher = increased risk; P = 0.003); an index of pancreatic beta-cell compensation for insulin resistance, defined as the product of the 30-min incremental plasma insulin:glucose ratio on a 75-g OGTT and the insulin sensitivity index from a hyperinsulinemic-euglycemic clamp (lower = increased risk, P = 0.009); and the basal glucose production rate after an overnight fast (higher = increased risk; P = 0.04). We conclude that postchallenge hyperglycemia, poor pancreatic beta-cell compensation for insulin resistance, and elevated endogenous glucose production during pregnancy precede the development of type 2 diabetes in young Latino women by at least 1-2 years.

Response of pancreatic beta-cells to improved insulin sensitivity in women at high risk for type 2 diabetes.

The purpose of this study was to examine the response of pancreatic beta-cells to changes in insulin sensitivity in women at high risk for type 2 diabetes. Oral glucose tolerance tests (OGTTs) and frequently sampled intravenous glucose tolerance tests (FSIGTs) were conducted on Latino women with impaired glucose tolerance and a history of gestational diabetes before and after 12 weeks of treatment with 400 mg/day troglitazone (n = 13) or placebo (n = 12). Insulin sensitivity was assessed by minimal model analysis, and beta-cell insulin release was assessed as acute insulin responses to glucose (AIRg) and tolbutamide (AIRt) during FSIGTs and as the 30-min incremental insulin response (30-min dINS) during OGTTs. Beta-cell compensation for insulin resistance was assessed as the product (disposition index) of minimal model insulin sensitivity and each of the 3 measures of beta-cell insulin release. In the placebo group, there was no significant change in insulin sensitivity or in any measure of insulin release, beta-cell compensation for insulin resistance, or glucose tolerance. Troglitazone treatment resulted in a significant increase in insulin sensitivity, as reported previously. In response, AIRg did not change significantly, so that the disposition index for AIRg increased significantly from baseline (P = 0.004) and compared with placebo (P = 0.02). AIRt (P = 0.001) and 30-min dINS (P = 0.02) fell with improved insulin sensitivity during troglitazone treatment, so that the disposition index for each of these measures of beta-cell function did not change significantly from baseline (P > 0.20) or compared with placebo (P > 0.3). Minimal model analysis revealed that 89% of the change from baseline in insulin sensitivity during troglitazone treatment was accounted for by lowered plasma insulin concentrations. Neither oral nor intravenous glucose tolerance changed significantly from baseline or compared with placebo during troglitazone treatment. The predominant response of beta-cells to improved insulin sensitivity in women at high risk for type 2 diabetes was a reduction in insulin release to maintain nearly constant glucose tolerance.

Gestational diabetes: antepartum characteristics that predict postpartum glucose intolerance and type 2 diabetes in Latino women.

We examined antepartum clinical characteristics along with measures of glucose tolerance, insulin sensitivity, pancreatic beta-cell function, and body composition in Latino women with gestational diabetes mellitus (GDM) for their ability to predict type 2 diabetes or impaired glucose tolerance (IGT) within 6 months after delivery. A total of 122 islet cell antibody-negative women underwent oral and intravenous glucose tolerance tests (OGTT; IVGTT), hyperinsulinemic-euglycemic clamps, and measurement of body fat between 29 and 36 weeks' gestation and returned between 1 and 6 months postpartum for a 75-g OGTT. Logistic regression analysis was used to examine the relationship between antepartum variables and glucose tolerance status postpartum. At postpartum testing, 40% of the cohort had normal glucose tolerance, 50% had IGT, and 10% had diabetes by American Diabetes Association criteria. Independent antepartum predictors of postpartum diabetes were the 30-min incremental insulin:glucose ratio during a 75-g OGTT (P = 0.0002) and the total area under the diagnostic 100-g glucose tolerance curve (P = 0.003). Independent predictors of postpartum IGT were a low first-phase IVGTT insulin response (P = 0.0001), a diagnosis of GDM before 22 weeks' gestation (P = 0.003), and weight gain between prepregnancy and the postpartum examination (P = 0.03). All subjects had low insulin sensitivity during late pregnancy, but neither glucose clamp nor minimal model measures of insulin sensitivity in the 3rd trimester were associated with the risk of IGT or diabetes within 6 months' postpartum. These results highlight the importance of pancreatic beta-cell dysfunction, detectable under conditions of marked insulin resistance in late pregnancy, to predict abnormalities of glucose tolerance soon after delivery in pregnancies complicated by GDM. Moreover, the association of postpartum IGT with weight gain and an early gestational age at diagnosis of GDM suggests a role for chronic insulin resistance in mediating hyperglycemia outside the 3rd trimester in women with such a beta-cell defect.

Threshold Amsler grid as a screening tool for asymptomatic patients on hydroxychloroquine therapy.

BACKGROUND/AIMS: Patients taking hydroxychloroquine (HCQ) are at risk of developing classic bull's eye maculopathy. Currently, the standard Amsler grid (AG) is one of the most useful methods to identify such lesions. However, AG is a suprathreshold target and may not detect relative central scotomas. The aim of this study was to determine if the threshold Amsler grid (TAG) test, which varies light transmission through two cross polarising filters, allows increased detection of scotomas caused by HCQ toxicity. METHODS: 56 rheumatological patients taking HCQ and 12 similar patients not taking HCQ were tested by AG, red Amsler grid (RAG), and TAG. RESULTS: No scotomas were observed in patients never treated with HCQ. Among patients who had been treated with HCQ, AG revealed scotomas in two of 56 (3.64%) patients; in contrast, six (10.7%) and 37 (66.1%) scotomas were identified by RAG and TAG testing respectively. Additionally, the average area of each scotoma detected by all three methods expanded from 34.5 square degrees of central field loss on AG testing to 71 square degrees on RAG and 117 on TAG. CONCLUSION: By decreasing the perceived luminance of the suprathreshold AG, TAG testing provides a novel alternative to detect shallow scotomas and areas of depressed retinal activity secondary to HCQ toxicity.

Hormonal choices after gestational diabetes. Subsequent pregnancy, contraception, and hormone replacement.

The effects of subsequent states of excess hormone exposure, for example, subsequent pregnancy, hormonal contraception, and hormonal replacement therapy, on the development of diabetes in women with prior gestational diabetes were assessed. Current literature examining the effect of parity, hormonal contraception, and hormonal replacement therapy in healthy women and women with previous gestational diabetes and current diabetes was reviewed. Subsequent pregnancy in women with prior GDM appears to triple the risk of subsequent diabetes. Low-dose progestin and estrogen combination oral contraceptives do not appear to clinically increase the risk of diabetes. Hormonal replacement therapy appears to provide the greatest reduction in coronary artery disease to women at greatest risk, i.e., those who have developed diabetes. Careful follow-up and metabolic surveillance should be provided when prescribing hormonal contraception or replacement therapy. In women with prior gestational diabetes, exposure to repeat pregnancy poses a greater risk for subsequent diabetes than does either an exposure to low-dose progestin and estrogen combination oral contraceptives or to postmenopausal hormonal therapy, both of which do not appear to increase the risk of diabetes.

Utility of fetal measurements in the management of gestational diabetes mellitus.

The metabolic management of gestational diabetes mellitus (GDM) during pregnancy traditionally has focused on maintenance of circulating maternal glucose concentrations in all patients within a range that is associated with a low rate of perinatal morbidity, especially morbidity related to excessive fetal growth and macrosomia. Clinical data reviewed elsewhere in this supplement provide guidelines for glycemic targets that appear to eliminate the excess risk to the fetus. However, because only a minority of infants are at risk for perinatal morbidity over the range of glycemia generally encountered in patients with GDM, attainment of those strict glycemic targets in all women with GDM requires implementation of self-monitoring of glucose and exogenous insulin therapy in many pregnancies that are not at risk. In this article, we review management approaches that take into account not only maternal glycemia, but also fetal growth and metabolic parameters in selecting GDM pregnancies for intensive metabolic therapy. The approaches can reduce the number of women with mild GDM who require self-monitoring of glucose and/or exogenous insulin therapy, thereby providing the potential to improve cost-effectiveness of antepartum management of GDM.

A randomized controlled trial using glycemic plus fetal ultrasound parameters versus glycemic parameters to determine insulin therapy in gestational diabetes with fasting hyperglycemia.

OBJECTIVE: To compare management based on maternal glycemic criteria with management based on relaxed glycemic criteria and fetal abdominal circumference (AC) measurements in order to select patients for insulin treatment of gestational diabetes mellitus (GDM) with fasting hyperglycemia. RESEARCH DESIGN AND METHODS: In a pilot study, 98 women with fasting plasma glucose (FPG) concentrations of 105-120 mg/dl were randomized. The standard group received insulin treatment. The experimental group received insulin if the AC, measured monthly, was > or =70th percentile and/or if any venous FPG measurement was >120 mg/dl. Power was projected to detect a 250-g difference in birth weights. RESULTS: Gestational ages, maternal glycemia, and AC percentiles were similar at randomization. After initiation of protocol, venous FPG (P = 0.003) and capillary blood glucose levels (P = 0.049) were significantly lower in the standard group. Birth weights (3,271 +/- 458 vs. 3,369 +/- 461 g), frequencies of birth weights >90th percentile (6.3 vs 8.3%), and neonatal morbidity (25 vs. 25%) did not differ significantly between the standard and experimental groups, respectively. The cesarean delivery rate was significantly lower (14.6 vs. 33.3%, P = 0.03) in the standard group; this difference was not explained by birth weights. In the experimental group, infants of women who did not receive insulin had lower birth weights than infants of mothers treated with insulin (3,180 +/- 425 vs. 3,482 +/- 451 g, P = 0.03). CONCLUSIONS: In women with GDM and fasting hyperglycemia, glucose plus fetal AC measurements identified pregnancies at low risk for macrosomia and resulted in the avoidance of insulin therapy in 38% of patients without increasing rates of neonatal morbidity.

Cost of non-insulin-dependent diabetes in women with a history of gestational diabetes: implications for prevention.

Women with gestational diabetes have a 50% risk of developing non-insulin-dependent diabetes mellitus within 10 years of delivery and thus constitute a well-defined target population for primary prevention. Current obstetric standards advocate universal screening of all pregnant women for gestational diabetes. Therefore, approximately half the reproductive-age United States population is screened for carbohydrate intolerance before the onset of overt disease. Continuation of dietary and behavioral changes initiated during pregnancy theoretically could delay or prevent progression to overt diabetes. We present an economic model of the health care dollars that could be saved by promoting postpartum life-style changes in women diagnosed with gestational diabetes. Assuming the incidence of diabetes could be reduced by 10, 25, or 50% in a national cohort of women with gestational diabetes, then 32, 140, or 331 million health care dollars could be saved over 10 years.

Type A behavior and exercise: a follow-up study of coronary patients.

Several previous studies have reported decreased Type A behavior pattern (TABP) after initiation of an exercise program. To determine if changes in TABP could be linked to exercise patterns in a cardiac rehabilitation program, both physical activity and TABP were measured in 81 male cardiac patients over a period of one year after hospitalization for an initial cardiac event. Changes in TABP scores were not associated with differences in activity patterns as measured by kilocalories per week of exercise, self-ratings of both job and leisure-time physical activity levels, or participation in a cardiac rehabilitation program. However, in Type A subjects there was a discrepancy between simple self-ratings of activity and more objective measures of exercise: subjects who had high TABP scores perceived themselves to be significantly more physically active than did subjects with lower TABP scores, even though the more objective estimates of physical activity were not associated with TABP scores.

Wood-dust exposures and cancer of the colon.

Previous studies of workers exposed to wood dusts have shown a decreased risk of cancer of the colon in these workers. However, none of these studies adequately controlled for potential confounders, such as physical activity, diet, and family history of colorectal cancer. The purpose of this case-control study was to evaluate the association between exposure to wood dust and risk for colon cancer after adjusting for potential confounders. Four hundred nineteen male cases of adenocarcinoma of the colon, identified from the Los Angeles County Cancer Surveillance Program, were individually matched to neighborhood controls based on gender and date of birth. Exposure to wood dust was associated with reduced risk of colon cancer that was partially masked before adjustment for confounders, and was limited to workers with frequent exposures that had begun at least 30 years before diagnosis [unadjusted and adjusted ORs, respectively, to exposures 5+ times a week beginning 30+ years before diagnosis = 0.63 (95% CI 0.36-1.13) and 0.39 (95% CI 0.20-0.77)]. This study provides additional evidence that heavy exposure to wood dusts may be associated with reduced risk of colon cancer in males after adjustment for other known causes of colon cancer.

Computer-assisted rescreening of clinically important false negative cervical smears using the PAPNET Testing System.

OBJECTIVE: To investigate the efficacy of the PAPNET Testing System and its ability to detect significant areas on clinically important false negative gynecologic smears. STUDY DESIGN: Sixty-two gynecologic smears that had been obtained from women studied in a previous case-control investigation, completed in 1987, and had originally been interpreted as negative were rescreened by two independent, blind cytotechnologist-cytopathologist teams. Twenty-nine of these "negative" smears were from 19 women who had been subsequently diagnosed with invasive squamous cell carcinoma and had self-reported a history of only negative gynecologic smears. Thirty-three smears were from 33 control women who did not develop cervical cancer. One team, at the University of Southern California (USC), manually rescreened the smears as part of the original study. The other team, at the University of California at Los Angeles (UCLA), recently used the PAPNET Testing System to rescreen the same smears. This computer-assisted system utilizes neural network technology to recognize and select potentially abnormal cell scenes on a conventionally prepared gynecologic smear. The PAPNET-selected scenes are displayed for review by trained cytologists, who ultimately diagnose the smear. RESULTS: Manual reevaluation of the smears by the USC team in 1987 resulted in the reclassification of 9 of the 29 case smears (31%) and 2 of 33 control smears (6%) as class II to V (atypical squamous cells of undetermined significance to invasive carcinoma). Using the PAPNET System to scan and review the same smears, the cytotechnologist at UCLA referred 24 case smears to the cytopathologist, who ultimately reclassified 12 of the 29 case smears (41%) and 5 of the 33 control smears (15%) as abnormal. CONCLUSION: This study supports the use of the PAPNET System as an effective, routine rescreener for the detection of clinically significant false negative gynecologic smears.

Levetiracetam rectal administration in healthy dogs.

BACKGROUND: Levetiracetam is used to manage status epilepticus (SE) and cluster seizures (CS) in humans. The drug might be absorbed after rectal administration and could offer a practical adjunct to rectal administration of diazepam in managing SE and CS. HYPOTHESIS: Levetiracetam is rapidly absorbed after rectal administration in dogs and maintains target serum concentrations for at least 9 hours. ANIMALS: Six healthy privately owned dogs between 2 and 6 years of age and weighing 10-20 kg. METHODS: Levetiracetam (40 mg/kg) was administered rectally and blood samples were obtained immediately before (time zero) and at 10, 20, 40, 60, 90, 180, 360, and 540 minutes after drug administration. Dogs were observed for signs of adverse effects over a 24-hour period after drug administration. RESULTS: CLEV at 10 minutes was 15.3 ± 5.5 µg/mL (mean, SD) with concentrations in the target range (5-40 µg/mL) for all dogs throughout the sampling period. Cmax (36.0 ± 10.7 µg/mL) and Tmax (103 ± 31 minutes) values were calculated and 2 disparate groups were appreciated. Dogs with feces in the rectum at the time of drug administration had lower mean Cmax values (26.7 ± 3.4 µg/mL) compared with those without (45.2 ± 4.4 µg/mL). Mild sedation was observed between 60 and 90 minutes without other adverse effects noted. CONCLUSIONS AND CLINICAL IMPORTANCE: This study supports the use of rectally administered levetiracetam in future studies of clinical effectiveness in the management of epileptic dogs.