Analysis of a femoral hip prosthesis designed to reduce stress shielding.

The natural stress distribution in the femur is significantly altered after total hip arthroplasty (THA). When an implant is introduced, it will carry a portion of the load, causing a reduction of stress in some regions of the remaining bone. This phenomenon is commonly known as stress shielding. In response to the changed mechanical environment the shielded bone will remodel according to Wolff's law, resulting in a loss of bone mass through the biological process called resorption. Resorption can, in turn, cause or contribute to loosening of the prosthesis. The problem is particularly common among younger THA recipients. This study explores the hypothesis that through redesign, a total hip prosthesis can be developed to substantially reduce stress shielding. First, we describe the development of a new femoral hip prosthesis designed to alleviate this problem through a new geometry and system of proximal fixation. A numerical comparison with a conventional intramedullary prosthesis as well as another proximally fixed prosthesis, recently developed by Munting and Verhelpen (1995. Journal of Biomechanics 28(8), 949-961) is presented. The results show that the new design produces a more physiological stress state in the proximal femur.

Myofibroblastoma of breast--an appraisal of cytoskeletal phenotypes.

Myofibroblastoma of the breast is a recently described entity. Since its first description in 1987, less than 50 cases have been reported. We present the first (reported) myofibroblastoma to be detected as a non-palpable mass on a routine screening mammogram and emphasize the importance of not mis-diagnosing this rare cellular lesion as malignant on frozen section. Review of the literature demonstrates changes in the clinical presentation of myofibroblastomas. Once considered more common in men than in women, myofibroblastomas are now being reported with increasing frequency in women. The age at presentation is a decade earlier, and not surprizingly, the size of the earlier detected lesion is smaller. Recently four different cytoskeletal phenotypes (V, VA, VAD and VD) of myofibroblastomas have been described, depending upon the vimentin (V), actin (A), and desmin (D) immunoreactivity. Whereas vimentin reactivity is universal, actin and desmin immunoreactivity is variable, desmin being more frequently positive than actin. As more is known about the clinical behavior of myofibroblastomas, their rate of recurrence and malignant potential, if any, the relationship of the cytoskeletal content to prognosis may become clearer. Currently, complete immunohistochemical analysis and electron microscopic examination of this interesting breast lesion is recommended. List of abbreviations-Vimentin (V), actin (A), and desmin (D), vimentin and actin (VA), vimentin and desmin (VD), vimentin, actin and desmin (VAD).

Male breast carcinoma: an evaluation of prognostic factors contributing to a poorer outcome.

BACKGROUND: Although breast cancer in men is far less common than breast cancer in women, it is associated with a less favorable prognosis. Conventional histopathologic features and new prognostic markers were evaluated to explain the less favorable survival outcome. METHODS: Forty-six consecutive male breast carcinomas were studied for size, histologic and nuclear grade, histologic subtype, presence of carcinoma in situ, nipple involvement, lymphovascular invasion, hormone receptor status, c-erbB-2 protein overexpression, and p53 protein accumulation. These findings were correlated with survival. RESULTS: Of the 46 carcinomas, 4 were noninvasive and 42 were invasive. In the invasive carcinomas, the median patient age was 64 years, and the median tumor size was 2 cm. The predominant histologic patterns were invasive ductal (45%) and mixed invasive ductal and cribriform (28%). Most tumors were of low histologic and nuclear grades (histologic grades: I, 17%; II, 50%; III, 33%; nuclear grade: I, 12%; II, 44%; III, 44%). Of those surgically staged, 22 patients (60%) were lymph node positive and 15 patients (40%) were node negative. Stage at presentation was higher than in women (0, 10%; 1, 17%; 2, 50%; 3, 13%; 4, 10%). The estrogen and progesterone receptor status was positive in 76% and 83% of tumors, respectively. Lymphatic vessel invasion (63%) and nipple involvement (48%) were also more common than in women. True Paget's disease of the nipple was not seen; all cases with nipple ulceration were the result of direct tumor extension to the epidermis. Of the 17 tumors tested, 41% were c-erbB-2 positive and 29% were p53 positive. Survival analysis was limited by the relatively small cohort size. Five- and 10-year adjusted overall survival rates for invasive tumors were 76 +/- 7% and 42 +/- 9%, respectively. Skin and nipple involvement (P = 0.03) and c-erbB-2-positivity (P = 0.03) were significant predictors of adverse survival. CONCLUSIONS: Male breast carcinoma presents in an advanced stage with less favorable survival, despite low histologic grade, high estrogen receptor content, and small size. Anatomic factors may have been responsible for the poor survival outcome (i.e., paucity of breast tissue and close tumor proximity to skin and nipple, facilitating dermal lymphatic spread and early regional and distant metastasis).

The role of immunocytochemical markers in the differential diagnosis of proliferative and neoplastic lesions of the breast.

The differential expression of keratins in myoepithelial and epithelial cells of the breast makes immunohistochemical distinction of lesions an attractive possibility. High molecular weight keratin, 34BE12, is a monoclonal antibody that recognizes keratins 1, 5, 10, and 14. Because myoepithelial cells predominantly express keratins 5 and 14 and epithelial cells predominantly express keratins 8 and 18, it is natural to assume that 34BE12 may be a good marker of myoepithelial cells but not epithelial cells. However, recent studies of the breast have reported conflicting results. To determine the potential role of 34BE12 in the breast, we studied by immunohistochemistry 19 tubular carcinomas, 14 radial scars, two microglandular adenoses, and 9 sclerosing adenoses, using monoclonal antibodies to high molecular weight keratin, smooth muscle actin, type IV collagen, and antiserum to S100 protein. Actin was negative in all 19 (100%) tubular carcinomas, but it delineated the myoepithelial cells in 22 of 23 (95.6%) benign lesions of sclerosing adenosis and radial scars; it was also negative in microglandular adenosis. In comparison, epithelial cytoplasmic 34BE12 reactivity was seen in 3 of 19 (15.8%) tubular carcinomas, whereas myoepithelial cells failed to react in 4 of 23 (17.3%) benign conditions. Antiserum to S100 protein had a similar disadvantage of labeling both epithelial and myoepithelial cells with reactivity in 5 of 19 (26.3%) tubular carcinomas. In microglandular adenosis, the epithelial cells were strongly S100 protein positive and focally 34BE12 positive, but no staining was observed for actin. Type IV collagen staining outlined distinct basement membranes in microglandular adenosis and other benign conditions but not in tubular carcinomas. However, staining for type IV collagen requires enzymatic pretreatment and is difficult to perform, especially in sclerotic breast tissue. In conclusion, actin appears to be the most consistent and specific marker for distinguishing tubular carcinomas from other benign conditions, and type IV collagen has a contributory role, whereas 34BE12 is less valuable than in prostatic biopsies.

Paget's disease of the nipple and angiosarcoma of the breast following excision and radiation therapy for carcinoma of the breast.

We report a case of bilateral angiosarcomas developing in breasts after radiation therapy. The angiosarcomas developed 7 years after the first dose and 3 years after the last dose of radiation. In addition, Paget's disease of the nipple was diagnosed in the right breast. c-neu overexpression was noted in the adenocarcinoma but not in the angiosarcoma. Neither tumor was immunoreactive for c-k-ras. The oncogenic expression of the radiation-induced angiosarcoma was different from that of the radiation-resistant adenocarcinoma. The simultaneous occurrence of angiosarcoma and Paget's disease of the nipple has not been reported previously. The importance of recognizing Paget's disease in post-irradiated breasts and complications of breast conservation therapy are stressed.

Ductal carcinoma in situ of the male breast.

BACKGROUND: Ductal carcinoma in situ (DCIS) of the male breast is an uncommon disease, accounting for approximately 7% of all male breast carcinomas. Compared with invasive carcinomas of the breast, the prognosis associated with DCIS in men is excellent; however, clinical features, pathology, and treatment of this disease are not well defined in the literature. METHODS: Records of 23 men with carcinoma of the breast treated at the Lahey Clinic from 1968 to 1991 were reviewed, revealing 4 patients with pure DCIS (17%). The reported management of DCIS in women is discussed in comparison with that of DCIS in men. RESULTS: Of the four patients with DCIS, the presenting complaint was a retroareolar mass in three patients and a bloody nipple discharge in one patient. The pathologic subtype was papillary in one patient and intracystic papillary in three patients. Two patients were treated with partial mastectomy alone. Disease recurred locally as DCIS in both patients, requiring mastectomy at 30 and 108 months. No lymph node metastases were found in the three patients who underwent axillary dissection. All four patients were alive without disease at 133, 120, 36, and 32 months of follow-up, respectively. CONCLUSIONS: Although the sample size was small, our patients and a review of the literature suggest that most DCIS in men is of the papillary type and that mastectomy without axillary dissection is the preferred treatment.

Pineal N-acetyltransferase, pineal and serum melatonin response to isoproterenol stimulation in underfed male rats.

Adult male rats were subjected to 4 weeks of 50% food restriction under lighting regimen of 14 h light and 10 h dark. The pineal response to isoproterenol (ISO) was determined. In the time-course study, animals were injected with 0.5 mg/Kg ISO subcutaneously (SC) and killed at different times up to 180 min post injection. In the dose-response study, various doses of ISO (0.2 mg/Kg to 5.0 mg/Kg) were injected intraperitoneally (IP) and animals were killed 120 min post injection. Body weight, pineal N-acetyltransferase (NATase), pineal and serum melatonin (MT) were determined. After 4 weeks of restricted feeding, body weight was reduced by 40%. In the time-course study, peak pineal NATase occurred 120 min post injection in the ad libitum fed animals. By contrast, the food restricted animals showed a gradual increase of pineal NATase up to 180 min post injection. In the dose-response study, the ad libitum fed animals demonstrated a dose dependent increase of pineal NATase up to 5 mg/kg dose. The food restricted animals, however, achieved their maximal pineal NATase at 1 mg/Kg dose with no further increment at 5 mg/Kg dose. These differences in responsiveness were also reflected in pineal and serum MT levels. These results indicate that underfed animals have abnormal pineal NATase, pineal and serum MT responses to ISO stimulation.

Differential effects of isoproterenol injections on the levels of pineal N-acetyltransferase, serum N-acetylserotonin and melatonin.

Rats housed under diurnal lighting conditions were either injected with isoproterenol (ISO), 0.5 mg/kg subcutaneous (SC) and sacrificed at different times up to 180 minutes afterwards, or injected with different doses of ISO (0.2 mg/kg to 5.0 mg/kg intraperitoneally (IP] and sacrificed 120 minutes later. Pineal N-acetyltransferase (NATase), serum N-acetylserotonin (NAS) and serum melatonin (MT) levels were determined. It was found that both pineal NATase and serum MT responded to the injection with peak increase at 120 minutes after the injection. This increase in pineal NATase and serum MT levels were also found to be dose-dependent. It was also observed that at 30 minutes after ISO injection, the serum MT level already demonstrated a significant increase which preceeded any increase in the pineal NATase activity. The underlying mechanism for this observation remains undetermined. Unlike serum MT and pineal NATase, there were no changes in serum NAS levels after injections of ISO at all the doses tested or up to 180 minutes after injection of the drug at 0.5 mg/kg dose SC. This suggests that serum NAS level is neither regulated by pineal NATase activity nor is the pineal gland the major source of NAS in circulation. This also indicates that serum NAS level is not influenced by beta-adrenergic stimulation.

Occurrence of genetic tumours in Triticum interspecies hybrids.

F1 interspecific hybrids involving nine tetraploid Triticum species were studied. Some developed leaf tumours at the seedling stage. Tumorous hybrids were restricted to crosses involving either T. timopheevi or T. araraticum as one parent. The hybrids from the rest of the crosses, including those of T. timopheevi × T. araraticum, were non-tumorous. Genetically divergent and non-integrated parental species appeared to be inducing spontaneous tumour formation in their hybrids.