Early detection of colorectal cancer by quantitative fluorescence image analysis of exfoliated cells

Early-stage colorectal cancer is potentially curable. In the present study, we applied quantitative fluorescence image analysis (QFIA) cytology to the detection of experimental colorectal cancer in a rodent model. QFIA cytology combines visual cytologic examination with quantitation of DNA content in single exfoliated cells. Cancer was induced by treating 110 rats with subcutaneous 1,2-dimethylhydrazine. Sequential colon washes were obtained weekly from each animal for 20 weeks. Control animals were treated identically except for the administration of carcinogen. Cells that were cytologically abnormal or had increased DNA content were found starting in the second week. By the eighth week, roughly 50 percent of animals had positive results, and this level remained approximately constant for the duration of the study. Tissue pathologic results were normal during weeks 1 to 7. Dysplasias became common during weeks 8 to 15 whereas most cancers appeared during weeks 16 to 21. These results indicate that QFIA cytology is a highly sensitive method for detecting even preneoplastic changes resulting from carcinogen administration and may prove useful in detecting human colorectal cancer.     

A stereological study of the human ovarian surface epithelium.

The surface of the ovary has been found to be composed of two types of epithelial cells called A and B cells which are found in their own respective zones, the A and B zones. A quantitative study was undertaken to determine the mean cell volumes and cell ultrastructure. Ovarian biopsies were taken from six women and A and B zones, having been identified by scanning electron microscopy, were re-embedded for transmission electron microscopy. Stereological measurements using point sampled intercepts were made on vertical sections and showed that B cells are significantly larger than A cells. The volume weighted mean cell volumes of the A and B cells were 237.3 microns 3 and 676.8 microns 3 respectively. The volume fractions of the nucleus and mitochondria were similar in the two cell types. Although the vesicle content of each type was similar, a large variation between cases made the interpretation difficult. The stereological tools used in this study proved to be easy and efficient estimators of surface cell ultrastructure and give an important direction for ultrastructural research.     

The estimation of mean nuclear volume in the diagnosis of breast carcinoma.

Sixty-two cases of breast pathology were randomly selected from the files of the Dunedin Public Hospital for evaluation of mean epithelial nuclear volume. The cases were comprised of both benign and malignant ductal epithelial disease, diagnosed in cytological smears or in histological sections. Nuclear volume in histological preparations was estimated by the stereological technique of point-line intercept measurements to derive volume-weighted mean volumes (vV). An index of the nuclear volume (Vi) of cytology smears was calculated from measurements of nuclear areas by either image analysis Vi(e) or point-line intercepts Vi(p). By all methods of analysis a clear distinction of nuclear volume was found between the benign [means for the cytology were 148 microns 3 (Vi(e)) or 246 microns 3 (Vi(p)), and 203 microns 3 (Vv) for the histology specimens] and malignant diseased cases [means for cytology: 524 microns 3 (Vi(e)) or 886 microns 3 (Vi(p)), and 587 microns 3 (vV) for the histology specimens].     

Histomorphometric features of hydatidiform moles in early pregnancy: relationship to detectability by ultrasound examination.

OBJECTIVE: The majority of partial (PHM) and complete (CHM) hydatidiform moles are diagnosed in early pregnancy. About half are identified as molar on ultrasonographic examination prior to evacuation. It is uncertain whether unsuspected cases represent an intrinsically different molar phenotype or are simply dependant on sonographer expertise. We measured a microscopic parameter, average villus diameter, of evacuated PHMs and CHMs to ascertain the cause of non-detection on ultrasound. METHODS: Fifty-four molar pregnancies were examined from the files of the Trophoblastic Disease Unit, in which results of an ultrasound examination prior to evacuation were known. In each, the average cross-sectional diameter of the largest 10 villi was recorded. Maximum villus diameters were compared between gestational age groups (<14 weeks and >or=14 weeks), and ultrasound detection groups (detected (d) and not detected (nd)). RESULTS: The average maximum villus diameter of the largest hydropic villi was significantly less in the first trimester for both PHMs and CHMs that were undetected by ultrasound examination compared to those identified as molar sonographically (P<0.001 and P<0.001, respectively). There was no significant difference in the maximum villus diameter between PHMs and CHMs that were not detected sonographically in the first trimester (P=0.44). Beyond 14 weeks of gestation, there was no significant difference between PHMs detected and undetected sonographically (P=0.88). CONCLUSION: The average diameter of the largest, most hydropic villi, is significantly greater in cases of PHMs and CHMs detected by ultrasound examination in the first trimester compared to that of those not detected sonographically, but beyond 14 weeks such differences are minimal. These findings suggest that, although sonographer expertise could potentially increase ultrasound detection rates somewhat for PHMs and CHMs, a significant proportion of cases demonstrate minimal hydropic change in the first trimester and are therefore likely to remain unidentifiable by ultrasound examination prior to evacuation, even with improved sonographer expertise.     

Laboratory and clinical evaluation of the impact Uni-Vent 750 portable ventilator

BACKGROUND: Transportation of critically ill, mechanically ventilated patients from intensive care units for diagnostic and therapeutic procedures has become common in the last decade. Maintenance of adequate oxygenation and ventilation during transport is essential. We evaluated the Impact Uni-Vent 750 portable ventilator in the laboratory and in the clinical arena to determine its usefulness during inhospital transport. MATERIALS & METHODS: In the laboratory, we determined the Uni-Vent 750's ability to assure tidal volume (VT) delivery in the face of decreasing compliance of a test lung and tested the alarm systems. Using a two-compartment lung model modified to simulate spontaneous breathing, we also evaluated the responsiveness of the demand valve. The clinical evaluation was accomplished by comparing arterial blood gas values and ventilator settings in the intensive care unit before transport to those during transport. RESULTS: As lung compliance was reduced from 0.1 to 0.02 mL/cm H2O [1.0 to 0.20 L/kPa], a slight, statistically insignificant decrease in delivered tidal volume was observed. All alarm systems operated according to manufacturer's specifications. The demand valve triggered appropriately with PEEP from 0 to 20 cm H2O [0 to 1.96 kPa]. Sensitivity settings less than -6 cm H2O [-0.59 kPa] sometimes resulted in inability to trigger the demand valve. During patient transport, arterial blood gas values and ventilator settings were comparable to those observed in the ICU. Because an FIO2 of 1.0 was used during transport, mean (SD) PaO2 was significantly greater 89 (26) vs 341 (78) [11.8 (3.5) vs 45.3 (10.4) kPa]. CONCLUSIONS: The Uni-Vent 750 is a reliable transport ventilator, capable of maintaining adequate oxygenation and ventilation in a majority of mechanically ventilated patients. The Uni-Vent 750's ability to (1) provide CMV, AMV, and SIMV; (2) provide low and high pressure alarms; and (3) provide PEEP compensation is unique among portable ventilators.     

Use of granulosa-luteal cell culture to evaluate low and high clinical responses to menotropin stimulation.

The cause of a poor response to human menopausal gonadotropin (hMG) remains unexplained. To determine whether aromatase activity of cultured granulosa cells obtained from relatively low estradiol (E2) responders (serum E2 < 1000 pg/ml) to hMG therapy differed from that of good responders (E2 > or = 1000 pg/ml), we prospectively compared serum E2 on the day of human chorionic gonadotropin administration to in vitro aromatase activity following a 72-h culture. Granulosa cells were obtained from seven women undergoing hMG therapy and oocyte aspiration. Follicle stimulating hormone (FSH) was added to one-half of the cultures. Serum E2 was determined by radioimmunoassay, and aromatase activity was determined indirectly by measuring tritiated water formed by aromatization of 1-beta [3H] androstenedione to estrogen in 1 h. In this study, luteinized granulosa cells from patients with a relatively low serum E2 produced less estrogen in cultures when compared to cells from higher responders (p < 0.01). Aromatase activity was not significantly increased by FSH in the relatively high responders, whereas FSH stimulated a significant increase in aromatase activity in cells from lower responders (p < 0.001). Our results indicate that the clinical response to hMG is at least partly due to the "quality" of granulosa cell aromatase activity. A clinically relevant "block" to FSH action may be present in vivo in low responders which can be reversed in culture by addition of FSH.