Stanley L. Inhorn

Comparison of conventional Papanicolaou smears and a fluid-based, thin-layer system for cervical cancer screening

Objective: To compare the cytologic diagnoses and specimen adequacy of a fluid-based, thin-layer preparation and conventional Papanicolaou tests. Methods: A total of 7360 women from six separate sites—three screening centers and three hospitals—participated in split-sample/matched-pair, double-masked clinical trials. A conventional Papanicolaou test was performed, after which residual material on the sampling device was rinsed into a fluid preservative from which a thin-layer slide (ThinPrep) was prepared using the ThinPrep 2000 automated slide processor (Cytyc Corp., Boxborough, MA). Conventional and ThinPrep slides were read independently. Cytologic diagnoses and specimen adequacy were classified using the Bethesda system. Results: For the three screening centers, 65% more diagnoses of low-grade squamous intraepithelial lesions and higher were made on the ThinPrep slides (P Conclusion: The fluid-based, ThinPrep method of sample preparation resulted in a statistically significant increase in cytologic diagnosis of cervical cancer precursors and in specimen adequacy compared with the conventional Papanicolaou testing method.

A new autosomal trisomy syndrome: multiple congenital anomalies caused by an extra chromosome

Summary Two patients are described who died in early infancy. Each displayed similar complexes of congenital anomalies of which the following ones were found in both: low-set and malformed ears, small mandible, flexion deformities of the fingers, anomalous feet, interventricular septal defect, spasticity with probable mental defect, and diverticulum of the intestine. The chromosome number was 47, the extra chromosome appearing to be the same one in each instance; it belongs to the E group in the classification of Patau and associates. 1 The mothers of both patients were of advanced age at the time of conception.

The D1 trisomy syndrome

This paper further defines the phenotype which results from trisomy for a particular autosome of the D group (13–15) in the cells of the developing embryo. From our 7 patients plus 7 additional cases reported by others, the principal pattern of anomalies in these grossly malformed babies is presented. Though there is variability in the expression of the D 1 trisomy from patient to patient, the total pattern of anomalies is specific enough to allow for clinical recognition in the nursery for newborn infants. As with the other autosomal trisomy syndromes (Downs syndrome and the 18 trisomy syndrome), this condition occurs more commonly at older maternal age.

The No. 18 trisomy syndrome.

Summary Trisomy of chromosome No. 18 results in a characteristic pattern of multiple congenital anomalies of which apparent mental retardation with moderate hypertonicity, lowset malformed ears, small mandible, flexion of the fingers with the index finger overlying the third, and severe failure to thrive constitute the most prominent clinical abnormalities. It usually leads to death in early infancy. The syndrome has been of sporadic occurrence. Its frequency increases with advancing maternal age.

A syndrome of multiple developmental defects including polycystic kidneys and intrahepatic biliary dysgenesis in 2 siblings

Two siblings were found to have a syndrome consisting of at least 13 comparable developmental defects including hypotonia, high forehead, camptodactyly, polycystic kidneys, intrahepatic biliary dysgenesis, incomplete descent of the gonads, and minor defects of the eyes, ears, palate, and hands. The patients failed to thrive, became jaundiced, and died in early infancy. The mother did not take any medication during either pregnancy. Cytologic studies did not reveal a chromosomal abnormality and the etiology is undetermined, but autosomal recessive inheritance is considered the most likely etiology.

Relationship of the wasting syndrome to lethality in rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin☆

Young adult male Sprague-Dawley rats treated with a LD95 dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exhibited a progressive reduction in feed intake and body weight until death occurred 15 to 32 days post-treatment. The time course and magnitude of weight loss and lethality of pair-fed control rats were essentially identical to that of TCDD-treated rats with each pair-fed control animal dying within 3 days of its TCDD-treated partner. Body composition analysis of the dead animals revealed that the total amounts of protein, fat, water, and ash in the carcasses of TCDD-treated and pair-fed control rats were each reduced to a similar extent. The temporal pattern of daily feed intake in TCDD-treated and pair-fed control rats (3 meals/day) or (1 meal/day) did not influence the results. Studies conducted at LD25-62 doses of TCDD in male Sprague-Dawley rats of different ages--weanling (90 g), young adult (275 g), and mature (450 g)--showed that the severity of the wasting syndrome in all age groups was greatest for animals that died. Also, young adult rats treated with a LD25 dose of TCDD that died displayed the same degree of hypophagia and weight loss prior to death as rats administered a LD95 dose. Histopathology of the liver and gastrointestinal tract was compared in TCDD-treated (LD95 dose) and pair-fed control rats killed 1 day before they otherwise would have died. Hepatocytes of TCDD-treated rats were enlarged relative to those of pair-fed control rats and contained nuclei that varied in size and number. Pair-fed control rats exhibited atrophy of the liver cords due to a decrease in the cytoplasmic volume of their hepatocytes. The stomach and small intestine of TCDD-treated rats were histologically similar to those of ad libitum-fed controls. In contrast, the glandular mucosa of the stomach of pair-fed control rats was ulcerated and the intestinal mucosa was atrophied. Stomach ulcers were the source of clotted blood found throughout the gastrointestinal tract of pair-fed control rats but not that of TCDD-treated animals. These findings demonstrate that hypophagia-induced weight loss is one of perhaps several responses that contribute to the death of TCDD-treated rats. That other responses are also involved is suggested by differences between pair-fed control and TCDD-treated rats in the weight and histopathology of certain organs. In addition, gastrointestinal blood loss contributes to the death of pair-fed control rats but not TCDD-treated animals.

Partial-trisomy syndromes

SummaryOne of the autosomes of the C group (6–12), C′, can sometimes be identified by a secondary constriction.A mother and her daughter, both afflicted with the oral-facialdigital (OPD) syndrome, are shown to be partially trisomic for an inner segment of C′, this segment having been inserted into chromosome 1. The other chromosome 1, the two chromosomes C′, and the rest of the complement of 46 chromosomes appear normal.In four other OFD patients no chromosomal abnormality was detected. Nonetheless, it is concluded that the OFD syndrome is generally caused by partial trisomy for a specific region of C′. The presence of the inserted extra segment would usually escape microscopical detection.

Hypophagia-Induced Weight Loss in Mice, Rats, and Guinea Pigs Treated with 2,3,7,8-Tetrachlorodibenzo-p-dioxin

C57BL/6 mice treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 360 micrograms/kg) displayed a significant reduction in feed intake and body weight until just before death, when they developed ascites and subcutaneous edema. This caused body weight of the mice that died to suddenly increase during the terminal stage of toxicity. TCDD-treated mice that survived did not develop ascites or edema, and maintained a body weight that was slightly less than that of pair-fed mice. Cumulative lethality in TCDD-treated mice (69%) was greater than that of pair-fed controls (14%). In guinea pigs treated with TCDD (2 micrograms/kg) both the time course and magnitude of hypophagia were closely associated with weight loss. Pair-fed guinea pigs did not lose quite as much weight as TCDD-treated animals because their total body water content was higher. Water intake in pair-fed guinea pigs was greater than that of TCDD-treated animals. The time course and magnitude of lethality tended to be similar in TCDD-treated guinea pigs (81%) and pair-fed controls (64%). In Fischer F-344 rats treated with TCDD (100 micrograms/kg) body weight loss was associated with a reduction in both feed and water intake. The time course and magnitude of weight loss in TCDD-treated and pair-fed rats was essentially identical. Lethality was higher in TCDD-treated rats (95%) than pair-fed control animals (48%). Taken together, these findings suggest that hypophagia is responsible for the loss of adipose and lean tissue in mice, guinea pigs, and rats treated with a LD70-95 dose of TCDD. Under these dosage conditions, weight loss contributes more to the lethality of guinea pigs than to that of Fischer F-344 rats or C57BL/6 mice.

Multidisciplinary approach to deep-seated lesions requiring radiologically-guided fine-needle aspiration

Fine‐needle aspiration (FNA) is a diagnostic modality that continues to improve in accuracy as training and experience accumulate. With increasing operator expertise and improved localization techniques, greater numbers of patients are able to benefit from FNAs performed on sites that are otherwise difficult or dangerous to reach by conventional surgery. We present a retrospective review of a 2‐yr experience with radiologically‐guided deep‐seated FNA. In 115 cases involving transthoracic and transabdominal sites, we achieved the following overall figures: 91.9% sensitivity, 100% specificity, 93.9% diagnostic accuracy, 100% positive predictive value, and 80.6% negative predictive value. Our results are compared to those in other series.

Use of fluorescent in situ hybridization to detect aneuploidy in cervical dysplasia.

Fluorescent in situ hybridization (FISH) with alpha satellite DNA probes for chromosomes 11 and X were applied to normal, atypical, ad dysplastic cervical‐vaginal cytology smears to evaluate the detection of hyperploidy in suspected abnormal cells. Forty‐six cases were obtained from fixed archival material. Eight cases with a morphological diagnosis of within normal limits (WNL) were directly selected to use as controls. The other 38 cases were blinded as study cases. These included five WNL, six ASCUS, six SIL‐LG, 16 SIL‐HG, four invasive squamous cell carcinomas, and one case of adenocarcinoma of the cervix. Cells with chromosome copy numbers suggesting hyperploidy (3–4 signals per chromosome specific probe) were found more often in higher grade dysplasia (Bethesda class SIL‐HG) cases and less often in lower grade lesions (SIL‐LG). All cases morphologically diagnosed as WNL were found to have normal copy number except for one control case which was hyperploid and, upon reexamination of the original slides, was upgraded from normal to atypical squamous cells of undetermined significance (ASCUS). Our FISH results are similar to those of previous studies involving flow cytometry and morphometry cytometry in which changes in ploidy correlated with progression toward higher grade lesions. However, FISH with enumeration probes offers a higher resolution view of the genome than is possible with flow cytometry or morphometry by allowing detection of specific chromosome changes in small numbers of affected cells in a routine cervical smear, and it may have the capacity to detect those cases in which progression toward high grade dysplasias is more likely. Diagn Cytopathol 1996;15:46–51.