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Biomedical subjects

D J Ferguson

Publications and source records attributed to D J Ferguson.

At least 163 records · Page 9Linked to original sources

Histologic features associated with long-term survival in breast cancer.

Three basic cytologic variants were identified among cases of infiltrating ductal carcinoma of the breast (NOS). These variants were found to have different distributions among patients surviving 25 years after mastectomy, compared with matched short-lived control subjects. Multivariate analyses indicated that recognition of these cytologic variants enhanced the prognostic value of tumor grade and blood vessel invasion. Patients with tumors designated here as histologic type C, which others have called invasive cribriform carcinoma, appear to have a higher probability of long-term survival than patients with other histologic subtypes. Since they account for approximately 20 per cent of 25-year survivors, they should be distinguished from patients with other types of infiltrating ductal carcinoma (NOS).

Adult↗

Weathering of hair in trichothiodystrophy.

The structure of hairs from three patients with sulphur-deficient hair, trichothiodystrophy, has been studied by light, plane-polarizing and scanning electron microscopy. Severe cuticular and secondary cortical degeneration was evident along almost the entire length of the hair shaft, with cuticle loss, trichorrhexis nodosa formation and trichoschisis. The severity of these changes varied between patients. The role of the cuticle in protecting hair from environmental damage is discussed.

Aging↗

Adenoid cystic carcinoma of the breast: a case with axillary lymph node metastasis.

A breast tumour with proven lymph node metastasis is conclusively characterized as an adenoid cystic carcinoma using immunocytochemistry and electron microscopy. The majority of tumour cells showed certain of the characteristic features of myoepithelial cells while the pseudocystic spaces contained large amounts of reduplicated basal lamina. A small proportion of tumour cells, however, showed epithelial differentiation with the formation of true lumina.

Aged↗

An ultrastructural study of mucoid carcinoma of the breast: variability of cytoplasmic features.

The ultrastructural characteristics of 14 cases of mucoid carcinoma of the breast, with different histological appearances, have been examined. Thirteen of the tumours were observed to consist of two populations of tumour cells, one showing secretory changes while the other group showed no evidence of activity. In one tumour only synthetically active cells were observed. Ultrastructurally, six different types of cytoplasmic granules, comprising typical mucin plus glycoprotein or protein-containing granules, were identified within the synthetically active tumour cells. The number of types of granules and the relative proportion of the various granules varied between tumours with only mucin granules present in all tumours. It would appear that synthetic pathways are activated in certain tumours which result in protein/glycoprotein granules associated with the argyrophilia observed histologically. In addition, the tumours varied with respect to luminal differentiation, presence of intracytoplasmic lumina, intracytoplasmic mucin pools, lipid droplets, ciliated cells and areas of calcification. The marked heterogeneity of the ultrastructural features of the mucoid carcinoma of the breast prevents the tumours from being readily divided into distinct subgroups.

Adenocarcinoma, Mucinous↗

A morphological study of experimental rabbit staphylococcal endocarditis and aortitis. I. Formation and effect of infected and uninfected vegetations on the aorta.

In this study the development of sterile thrombic vegetations on the aorta resulting from catheterization and the effect of subsequent infection with Staphylococcus aureus were examined by light and electron microscopy. Thrombi of various sizes, comprising fibrin, platelets and a few leucocytes and erythrocytes, develop on the damaged surface of the aorta with minimal changes in the underlying aortic wall. After intravenous inoculation of Staph. aureus most vegetations become infected, as shown by the presence of bacterial colonies, and the underlying aortic wall is markedly inflamed. The inflammatory cells invade the wall from the base of the aorta and cause swelling plus disruption of the elastic laminae with ulceration of the luminal surface in some cases. This structural damage appears to be a direct result of the bacterial infection of the lesions on the luminal surface.

Animals↗

A morphological study of experimental staphylococcal endocarditis and aortitis. II. Inter-relationship of bacteria, vegetation and cardiovasculature in established infections.

The inter-relationship of the bacteria, vegetations and cardiovasculature was studied by light and electron microscopy in experimental staphylococcal endocarditis and aortitis in acute and fatal infections. A specific spatial relationship was observed with the majority of bacterial colonies located along the junction between the cardiovasculature and the overlying thrombic vegetation. The bacterial colonies within the vegetations on the ventricular and aortic walls were smaller and embedded in a thick layer of thrombus with certain colonies showing evidence of bacterial cell death. By comparison, the lesions on the aortic valve consisted of large masses of bacteria with little or no thrombic coating. The structural damage to the aortic valve appeared to be the direct result of bacterial invasion into the connective tissue of the cusp. The acute nature of the disease may be related to bacterial destruction of the aortic valve whereas the colonies within the aortic wall vegetations are probably the source of 'resistance' to antibiotic treatment.

Animals↗

A controlled trial of extended radical mastectomy.

One hundred twenty-three women younger than 70 years of age and at clinical Stages I or II were enrolled in a randomized clinical trial of radical versus extended radical mastectomy. The 5-year survival rates in the radical and extended radical groups were 75 +/- 6.7% and 80 +/- 6.7%, respectively. (Cox P value for comparison of survival curves = 0.32.) Of the total series, 112 were treated by the same surgeon and confirmed pathologically as having invasive mammary carcinoma. In this more homogeneous subgroup, the 5-year survival rates for the radical and extended radical groups were 71 +/- 7.6% and 85 +/- 6.2%, respectively (P = 0.09). For patients from this subgroup with central or medial tumors, the 5-year survival rates were 66 +/- 10% and 88 +/- 8.2%, respectively (P = 0.06). For patients with lateral tumors, the 5-year survival rates were nearly equal: 79 +/- 11% and 81 +/- 9.7%, respectively. The findings in a nonrandomized series of similar patients were comparable. The results are not definitive, but suggest an advantage of extended radical mastectomy over radical mastectomy for patients with central or medial tumors. Continued follow-up of the randomized series may lead to more conclusive results.

Adult↗

Distribution of dense core granules in normal, benign and malignant breast tissue.

In this study breast tissue from 114 patients has been examined ultrastructurally for dense core granules (DCG). The tissue included examples of normal 'resting', pregnant and lactating breast plus various benign and malignant lesions. DCG were observed in low numbers in the apical cytoplasm in a proportion of the examples of 'resting' and pregnant breast tissue but were absent in the lactating patients. The incidence appeared to relate to hormonal changes. They were present in 50 per cent of the benign lesions examined. DCG were also observed in a high proportion of the ductal, lobular and tubular carcinomas examined and were associated with luminal differentiation. In the mucoid carcinomas over half the tumours possessed some DCG with large numbers of DCG present within certain of the malignant cells in two cases. It is possible that the granules could be related to mucin secretion. Therefore, in normal, benign and malignant (with the exception of mucoid carcinoma) breast tissue the presence of DCG would appear to be related to hormonal changes and represent prelactational differentiation rather than providing evidence of neuroendocrine differentiation. We emphasize the need for a comprehensive knowledge of the normal morphological variations within a tissue before attempting to interpret its tumours.

Adolescent↗

Intraepithelial lymphocytes and macrophages in the normal breast.

In this study the presence of intraepithelial cells within the normal breast parenchyma was investigated by electron microscopy and immunocytochemistry. Cells were observed which could be differentiated from the epithelial and myoepithelial cells by their cytoplasmic and nuclear morphology and the absence of cell junctions. Two cell types (lymphocytes and macrophages) were identified ultrastructurally and the bone marrow origin of the cells was confirmed by immunocytochemistry. The intraepithelial lymphocytes and macrophages were present in all samples irrespective of the physiological state. In the "resting", pregnant, and lactating breast the majority of cells were lymphocytes while in the involuting breast there was a marked increase in the proportion of macrophages. The rarity of lymphoma of the breast may be related to the relatively small amount of lymphoid tissue present and the passive nature of the environment.

Antibodies, Monoclonal↗

Ultrastructural characterisation of the proliferative (stem?) cells within the parenchyma of the normal "resting" breast.

In this study the proliferative (stem?) cells within the parenchyma of the normal "resting" breast were characterised by the ultrastructural examination of 60 mitotic cells. The parenchyma consists of epithelial and myoepithelial cells plus a few intraepithelial lymphocytes and macrophages. The majority of mitotic cells were randomly distributed throughout the lobules with a few present in ducts. In all cases the cells were identified as luminally positioned polarised epithelial cells. The proliferating cells had similar cytoplasmic features and were indistinguishable from adjacent interphase epithelial cells. No evidence was found for the division of subluminal epithelial or myoepithelial cells. These observations would be consistent with a single cell type giving rise to both epithelial and myoepithelial cells.

Adolescent↗

Isolation of intestinal mononuclear cells: factors released which affect lymphocyte viability and function.

Whether toxic or immunomodulatory factors are released during the collagenase digestion phase of the isolation of mononuclear cells from human intestinal mucosa was investigated by assessing the effect of the collagenase supernatant on the viability and natural killer activity of normal peripheral blood mononuclear cells. Three hours' incubation in collagenase supernatant suppressed natural killer activity by 25 +/- 4% and decreased the viability of peripheral blood mononuclear cells by 11 +/- 2%. The ability of collagenase supernatants to kill 51Cr-labelled peripheral blood mononuclear cells over four hours was assessed in 16 collagenase supernatants, eight of which produced lysis of 20 +/- 4%. There was no ultrastructural evidence of early degenerative changes in the viable intestinal mononuclear cells fresh from the isolation process or in peripheral blood mononuclear cells incubated in collagenase supernatant. Because prostaglandins are known to inhibit natural killer activity, PGE was measured in 20 collagenase supernatants by radioimmunoassay and found to be high at 27.5 +/- 4.0 ng/ml. Addition of indomethacin to the collagenase medium, however, failed to abolish the inhibitory effect of collagenase supernatant on natural killer activity and did not increase the natural killer activity of isolated intestinal mononuclear cells. The release of cytotoxic and immunomodulatory factors during the isolation of intestinal mononuclear cells indicates the necessity for careful assessment of the potential effects of the isolation process on any function being examined and casts doubt upon the relationship between in vitro findings and in vivo functional capabilities.

Cell Separation↗

Long-term survival of patients with localized diffuse histiocytic lymphoma.

From January 1970 to March 1981, localized diffuse histiocytic lymphoma (DHL) was identified in 31 patients by exploratory laparotomy and splenectomy (pathologic stage I, 17 patients; pathologic stage II, 14 patients) at the University of Chicago. The median follow-up time was 72 months. All patients were previously untreated and received radiation therapy as their primary treatment modality. Chemotherapy was administered only at the time of relapse. All but two patients achieved a complete remission (CR) with radiation therapy. The actuarial disease-free survival for patients with stage I disease is 94% at 5 years and 72% at 10 years. For stage II disease, the disease-free survival is 56% at 5 years and 31% at 10 years. The difference in the disease-free survival between stage I and II is statistically significant (P = .02). The survival at 10 years is 70% for stage I disease and 46% for stage II disease. Five patients had documented relapses (four had stage II disease). Only two of those who relapsed achieved a second CR with salvage chemotherapy. Our data show an excellent outcome in patients with pathologic stage I disease, indicating that a high percentage of these cases can be cured with radiotherapy alone. Patients with clinical stage II disease might be served better with chemotherapy.

Adolescent↗

Pathologic stages IA and IIA Hodgkin's disease: results of treatment with radiotherapy alone (1968-1980).

Between Jan 1, 1968, and Dec 31, 1980, 108 previously untreated patients with Hodgkin's disease pathologic stages (PSs) IA (29 patients) and IIA (79 patients) initially received radiotherapy alone. One postoperative death (due to pulmonary embolus) (0.9%) occurred, with one serious complication (0.9%). Between 1968 and 1973, patients were randomized to receive either involved field radiation treatment (RTIF) or extended field radiation treatment (RTEF). Since 1973 all patients have received RTEF, 4,000 cGy in four to five weeks, with a median follow-up of 7.4 years. Complete remission (CR) was achieved in 102 patients (94.4%), with no significant difference according to treatment or stage. Of the complete responders, 25 patients relapsed: 5/15 RTIF and 20/87 RTEF (P = .6). Twenty-one of 25 relapsing patients achieved a second CR. Disease free survival rates at five and ten years constituted: PS IA, 78.6% for both; PS IIA, 74.8% and 73.1% (P = .6); RTEF, 76.7% for both; RTIF, 73.3% and 66.7% (P = .7). Eighteen patients have died: eight of recurrent lymphoma, two of pulmonary embolus, one each of myocardial infarction, pulmonary fibrosis, and acute nonlymphocytic leukemia (ANLL) (following salvage chemotherapy), and one of diffuse histiocytic lymphoma (DHL). Four patients died in remission of unrelated causes. Actuarial survival rates at five and ten years constituted: PS IA, 95.7% and 72.4%; PS IIA, 89.6% and 81.4% (P = .3); RTIF, 93.7% for both; RTEF, 90.7% and 71.2% (P = .2). Age, sex, number of sites, and mediastinal involvement did not influence the outcome. Acute toxicity was modest and more frequent among those receiving RTEF (P = .08). Chronic toxicity (onset more than 30 days after completion of treatment) was identified in 16 patients: 1/16 RTIF; 15/92 RTEF (P = .5). Three patients developed a second malignancy: one carcinoma of the cervix in situ; one ANLL (following salvage chemotherapy); and one DHL of the stomach. At least 75% of patients with PS IA and IIA Hodgkin's disease were cured by radiation alone, with a risk of secondary malignancy following radiation alone of 0.9%. Since the majority of relapsing patients were successfully salvaged by chemotherapy, radiation alone appears to be the initial treatment of choice in this group of patients.

Actuarial Analysis↗

Late effects of adjuvant radiotherapy for breast cancer.

Complications requiring in-hospital treatment were observed in 24 of 221 consecutively treated patients (11%) who were followed from 8 to 42 years after postmastectomy irradiation. There were four sarcomas of the treated chest wall, three squamous carcinomas (two in the esophagus), two angiosarcomas of the swollen homolateral arm, nine chronic ulcers, five respiratory insufficiencies, six pathologic fractures of the radiated shoulder or ribs, two fatal cardiomyopathies, one persisting leukopenia with fatal brain abscess, and one severe neurovascular impairment of the arm. In a comparable group of 394 consecutive postmastectomy patients who were not irradiated, one similar event, a myxosarcoma of an unswollen arm, was observed. Only long-term follow-up can determine the ultimate risks of radiotherapy.

Adult↗

An ultrastructural study of lactation in the human breast.

In this study the morphological features of lactation in the human breast were examined by scanning and transmission electron microscopy. The lactating lobules comprised large numbers of interconnecting acini which were lined by a single layer of epithelial cells with underlying myoepithelial cells. Marked variations were noted in the shape of the epithelial cells. The myoepithelial cells formed an open meshwork of interconnecting cytoplasmic processes packed with myofibrils. The basal cytoplasm of the epithelial cells was packed with rough endoplasmic reticulum while the apical cytoplasm contained a hypertrophic Golgi body, numerous vacuoles (a few of which contained casein micelles), a number of lipid droplets and small coated and uncoated vesicles. The lipid droplets were released by progressive protrusion from the apical surface. They remained covered by the plasmalemma and were finally budded off into the lumen. In certain cases a portion of cytoplasm was released with the lipid droplet. The vacuoles and small vesicles fused with the plasmalemma and released their contents by exocytosis. Within the samples the majority of epithelial cells were actively lactating although examples of undifferentiated "resting" and dead (lysed) cells were also identified.

Breast↗