Synthesis and DNA-binding properties of dinuclear platinum(II)-amine complexes of 1,7-dicarba-closo-dodecaborane(12).

The first examples of platinum(II)-amine complexes containing a dicarba-closo-dodecaborane(12) (carborane) moiety are described; preliminary in vitro DNA-binding experiments indicate that the complexes are capable of targetting plasmid DNA.

Variability in serotonin and enterochromaffin cells in patients with colonic inertia and idiopathic diarrhoea as compared to normal controls.

AIM: To evaluate differences in distribution, density and staining intensity of enterochromaffin cells (EC) and serotonin cells (SC) in the colonic mucosa of patients with colonic inertia (CI), idiopathic diarrhoea (ID) and a control group. METHODS: Three groups were studied: 19 patients' colons after subtotal colectomy for CI, and 17 patients' biopsies for diarrhoea (>3 bowel movements/day) with histological findings of normal mucosa (excluding microscopic, eosinophillic and collagenous colitis). The third group included 15 patients who underwent colonoscopy and biopsy for indications other than constipation, inflammatory bowel disease, diarrhoea or neoplasm (control group). Specimen blocks were obtained in each case from the right and left colon. Immunohistochemical staining for EC and SC were done on 4 micro m sections from Hollandes fixed, paraffin embedded tissues with primary rabbit antibody against chromagranin A or serotonin, and biotynylated secondary antibody and enzyme labelled streptavidin. RESULTS: The number of EC in the mucosa of the left colon in patients with CI (16.8 +/- 10.2) and ID (19.9 +/- 9.7) were significantly higher than they were on the right side (CI: 9.4 +/- 6.0, ID: 12.1 +/- 5.3). However, there were no significant differences between the left and right sides in the control group (L: 10.3 +/- 5.3; R: 13.4 +/- 7.6). Although the quantity of EC in the left colon in both patients with CI (P < 0.05) and ID (P < 0.01) were significantly higher than in the controls, there was no significant difference between CI and ID. In both the right and left colon, the percentage of EC with low positive density was significantly higher (P < 0.01) while those cells with moderate or low staining intensity were significantly lower in patients with CI than in either patients with ID or control group. In patients with CI, the quantity of SC in the mucosa of the left colon (12.1 +/- 6.4) was higher than in the right (CI: 7.9 +/- 3.6; control 4.6 +/- 3.3; ID 4.6 +/- 2.9) (P = 0.0057). In contrast there was no significant difference in SC in either the ID or control groups. The quantity of SC in both sides of the colon was significantly higher both in patients with CI as compared to the control group (P < 0.01) and patients with CI vs. patients with ID (L = P < 0.01; R = P < 0.05). There was a significantly positive correlation between the numbers of EC and SC in patients with CI (L: r = 0.5425, P < 0.05; R: r = 0.745, P < 0.01). CONCLUSION: In patients with CI, EC increases possibly due to an increase in SC. Conversely, in patients with ID, the EC increase results from peptides other than SC. Our results suggest that different aetiological factors contribute to ID and CI.

Reparative changes and the false-positive/false-negative Papanicolaou test: a study from the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology .

CONTEXT: Reparative changes can be a diagnostic challenge on Papanicolaou tests and must be distinguished from epithelial cell abnormalities. Both squamous intraepithelial lesions (SIL) and carcinoma may be underdiagnosed as repair. This study examines laboratory and cytologist performance in the diagnosis of repair. OBJECTIVES: To determine if laboratories and cytologists can consistently distinguish reparative changes from SIL and carcinoma and to document how often SIL and carcinoma are mistaken for repair in a standardized educational slide program. DESIGN: Results for reparative changes, SIL, and carcinoma slides from the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology for 1998 were analyzed. Only results from validated referenced slide responses were used. RESULTS: The concordancy rate for reparative-change slides, that is, any response of within normal limits or benign cellular changes, ranged from 91% to 94% for cytotechnologist, pathologist, and laboratory responses. False-negative rates for squamous carcinoma and adenocarcinoma, high-grade SIL, and low-grade SIL ranged from 0.47% to 5.41%; the proportion of false-negative diagnoses of reparative changes ranged from 24% to 62% of all discordant responses. CONCLUSIONS: Of all benign cellular changes and within normal limits categories in the Interlaboratory Comparison Program in Cervicovaginal Cytology, repair most often elicits a false-positive laboratory response. Underdiagnosing epithelial abnormalities as repair is also a source of false-negative Papanicolaou test results.

Interobserver variability in subclassification of squamous intraepithelial lesions: Results of the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology.

OBJECTIVE: To determine whether, on a national cytology proficiency test, a competent cytologist can consistently distinguish grades of squamous intraepithelial lesions. DESIGN: Results for low- and high-grade squamous intraepithelial lesion referenced slides from the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology for 1996 and 1997 were analyzed including educational, nongraded vs graded validated slides. RESULTS: The discrepant rate between low- and high- grade lesions ranged from 9.8% to 15% for cytotechnologist, pathologist, laboratory, and all responses. There was a statistically significant difference in performance on graded, validated slides vs educational slides with better performance on validated slides. CONCLUSION: This significant interobserver variability in subclassification of squamous lesions should be considered in management guidelines for abnormal Papanicolaou test results and implementation of national cytology proficiency testing.

Cytologic evidence of extensive keratotic reaction in women exposed to diethylstilbestrol in utero.

Squamous mucous membranes and squamous metaplastic epithelium sometimes undergo hypermaturation with the production of a keratin layer. Anucleated keratotic squamous plaques in smears are generally recognized as cytologic evidence of this altered maturation. This keratotic reaction was quantified in cytologic smears from 191 women exposed in utero to diethylstilbestrol (DES). Keratotic reaction was observed in the vaginal smear in 40% of the cases, in the cervical smear in 26% and in the endocervical smear in 19%; overall, a keratotic reaction was observed in at least one specimen from 48% of the women. These frequencies are higher than those reported in other studies. The observed frequency was age related. The significance of the hyperkeratosis, including its possible relationship to a lower dysplasia rate among DES-exposed women, is unclear. No conclusions can be drawn until more is known about behavioral factors in DES-exposed women.

PIP: Squamous mucus membranes and squamous metaplastic epithelium sometimes undergo hypermaturation with the production of a keratin layer. Anucleated keratotic squamous plaques in smears are generally recognized as cytologic evidence of this altered maturation. This keratotic reaction was quantified in cytologic smears from 191 women exposed to diethylstilbestrol (DES) in utero. Keratotic reaction was observed in the vaginal smears in 40% of the cases, in the cervical smear in 26%, and in the endocervical smear in 19%; overall, a keratotic reaction was observed in at least 1 specimen from 48% of the women. These frequencies are higher than those reported in other studies. The observed frequency was age related. The significance of the hyperkeratosis, including its possible relationship to a lower dysplasia rate among DES-exposed women, is not clear. No conclusions can be drawn until more is known about behavioral factors in DES-exposed women.

Double stapled ileal pouch anal anastomosis (DS-IPAA) for mucosal ulcerative colitis (MUC): is there a correlation between the tissue type in the circular stapler donuts and in follow-up biopsy?

PURPOSE: This study aims to assess the correlation between the tissue types found in the circular stapler donut at the time of initial double-stapled ileal pouch-anal anastomosis (DS-IPAA) and during subsequent periodic routine random biopsy. Secondarily, we sought to assess the risk of dysplasia, carcinoma or mucosal ulcerative colitis (MUC) recurrence in the retained mucosa. METHODS: The pathology reports of 91 patients (48 males, 43 females) who were operated upon for MUC from September 1988 to June 1997 and were reviewed and had two follow up visits for biopsy. The histological features of the distal donuts and biopsies of retained mucosa obtained at yearly interval follow-up were assessed in order to determine the epithelial tissue type (columnar, transitional and squamous), inflammation, recurrence of MUC and presence of dysplasia or malignancy. RESULTS: Median age at surgery was 43 (range 15-71) years and duration of MUC was 9.6 (range 0.3-42) years prior to surgery. The anastomosis was performed at a median height of 1.0 (range 0-2.5) cm cephalad to the dentate line and biopsy follow-up was undertaken at median 34 (range 2-110) months after DS-IPAA. The distal donuts were analysed in all cases, as were 305 follow-up biopsies (median 3.4; range 1-7 per patient). Although columnar epithelium (CE) was found in 62 (68%) donuts, it was absent on follow-up biopsy in 16 (26%) of these patients. Conversely, although no CE was identified in 29 (32%) donuts, it was identified in 11 (38%) of these patients during follow-up biopsy. CE in the donut was a significant predictor of CE in subsequent biopsies (P = 0.0012). The histological features consistent with MUC were seen in the biopsies from the retained mucosa in 15 (16%) patients from 0.3 to 7.6 years after DS-IPAA. While eight (9%) patients exhibited dysplasia or adenocarcinoma in the excised colon or rectum, none of the patients had either dysplastic changes or carcinoma within the retained mucosal biopsies. CONCLUSION: The correlation between CE in the circular stapler donut and at follow-up biopsy was high. However since CE developed in some patients in whom no CE was present in the distal donuts, regardless of the epithelial tissue type finding at the time of DS-IPAA, periodic follow-up biopsy should be obtained.