Diagnosis and management of phyllodes tumour of the breast: experience of 33 cases at a specialist centre.

This study reviews the diagnosis and management of a consecutive series of 33 phyllodes tumours of the breast treated at The Royal Marsden Hospital, Sutton, between 1981 and 1992. The mean age of patients at presentation was 41 years (range 15-67 years). Tumours occurred equally in each breast and were significantly more common in the upper outer quadrant (chi 2 = 12.7, df = 3, P < 0.01). Clinical features (age, tumour size, palpation) and diagnostic investigations (mammography, ultrasound and fine needle aspiration cytology) were not sufficiently accurate to reliably make a preoperative diagnosis or predict histological type (benign, borderline or malignant). The diagnosis of phyllodes should be considered in patients aged 30-50 years with an apparent fibroadenoma. Of the patients, 66% underwent wide excision or mastectomy resulting in a favourable local recurrence rate of 14%. Our experience and review of the literature suggests that adequate local surgery is the treatment of choice and adjuvant treatments have no place in the routine management of phyllodes tumours. Regional lymph nodes were not involved in any of our patients and axillary dissection is not indicated.     

Primary infantile-onset esotropia — 20 years later

Of 286 cases of primary infantile onset esotropia operated upon early, 42 were reviewed after 20 years. Four of them achieved normal bifoveal stereoscopic vision (40 arc) despite the fact that at review after 3–4 years of age none had better stereopsis than 80 arc. Emphasis is laid on three main factors which may influence the result of early surgery and on the eventual attainment of normal binocularity, i.e. pre-operative alternating occlusion, accurate and repetitive muscular surgery, post-operative occlusion until parallelism is achieved in all directions of gaze and meticulous follow-up into the mid-teens.Dedicated to Dr. G.K. von Noorden on the occasion of his 60th birthday     

Induction and depression of cytochrome P-450-dependent mixed-function oxidase by a cloned consensus alpha-interferon (IFN-alpha CON1) in the hamster

A novel analogue of human alpha-interferon (IFN-alpha CON1) was tested for its ability to modify the hepatic cytochrome P-450-dependent mixed-function oxidase system in the hamster. This cloned interferon was derived by selecting the most frequently observed amino acid sequences at each position in the known human alpha-interferon subtypes. IFN-alpha CON1 had a biphasic effect on cytochrome P-450 and related drug biotransformation in the hamster causing an initial increase followed by a significant depression. IFN-alpha CON1 also had a biphasic effect on cytochrome P-450 in the lung, adrenal and spleen but only a depressant effect in the kidney. This effect was not due to morphological damage and followed the species specificity for this type of interferon. Both the increase and the decrease in cytochrome P-450 could be prevented by the administration of the protein synthesis inhibitor puromycin. Various isozymes of cytochrome P-450 induced by phenobarbital, beta-napthaflavone and clofibrate were also depressed by this interferon. The results presented in this report suggest that IFN-alpha CON1 interferon will likely depress drug biotransformation in humans because the antiviral effects and the "anti-cytochrome P-450" effect of interferons cannot be separated, and this interferon has antiviral properties in both hamster and human cells. Clinically relevant drug interactions may be common during the concomitant use of this interferon and other drugs that are metabolized by cytochrome P-450.     

Rosai-Dorfman Disease: A previously unreported association with Sickle Cell Disease

Background  

Rosai-Dorfman Disease is an uncommon benign systemic histio-proliferative disease. This is the first time the disease, although more common in people of African descent, is described in association with Sickle cell disease.     

Oriented astroglial cell growth on micropatterned polystyrene substrates

In an effort to develop a permissive environment for neural stem cell differentiation, directional growth of astrocytes has been achieved on polymer substrates in vitro. Manipulating a combination of physical and chemical cues, astrocyte adhesion and alignment in vitro were examined. To provide physical guidance, micropatterned polymer substrates of polystyrene (PS) were fabricated. Laminin was selectively adsorbed onto the grooves of the patterned surface. Rat type-1 astrocytes were seeded onto the micropatterned PS substrates, and the effects of substrate topography and the adsorption of laminin to the PS substrates on the behavior and morphology of the astrocytes were explored. The astrocytes were found to align parallel to the micropatterned grooves at initial seeding densities of approximately 7500, 13,000, and 20,000 cells/cm(2) due to the effects of the physical and chemical guidance mechanisms. Adsorbing laminin in the microgrooves of the micropatterned PS substrates improved cell adhesion and spreading of cytoskeletal filaments significantly. At these initial seeding densities, over 85% astrocyte alignment in the direction of the grooves was achieved on the micropatterned PS substrates with laminin adsorbed in the grooves. This combination of guidance cues has the potential to provide a permissive substrate for in vivo regeneration within the central nervous system.     

Serial linkage of target selection for orienting and tracking eye movements

Many natural actions require the coordination of two different kinds of movements. How are targets chosen under these circumstances: do central commands instruct different movement systems in parallel, or does the execution of one movement activate a serial chain that automatically chooses targets for the other movement? We examined a natural eye tracking action that consists of orienting saccades and tracking smooth pursuit eye movements, and found strong physiological evidence for a serial strategy. Monkeys chose freely between two identical spots that appeared at different sites in the visual field and moved in orthogonal directions. If a saccade was evoked to one of the moving targets by microstimulation in either the frontal eye field (FEF) or the superior colliculus (SC), then the same target was automatically chosen for pursuit. Our results imply that the neural signals responsible for saccade execution can also act as an internal command of target choice for other movement systems.     

The common heat shock protein receptor CD91 is up-regulated on monocytes of advanced melanoma slow progressors

Despite advances in our understanding of tumour immunology there is no therapy of proven survival benefit for advanced melanoma. Nevertheless, disease progression is slow in a small proportion of patients with metastatic melanoma, suggesting a contribution to outcome from host factors. Recent data have indicated the importance of the heat shock protein receptor CD91 in immune responses to, and progression of, infectious disease. Here we investigate the relationship between CD91 expression and outcome in malignancy. Rare melanoma patients were recruited with advanced disease that was progressing unusually slowly. CD91 expression on their monocytes was compared with control patients with more typical rapidly advancing metastatic disease. Th1 and Th2 cytokines, as well as innate and adaptive immune subsets, were also measured in the two groups. A significant increase in median CD91 expression levels was observed in slow progressors (P = 0.006). There were no differences in other immune subset markers or inflammatory cytokines. The ability of CD91 to internalize and cross-present tumour antigens through the major histocompatibility complex class I pathway may maintain CD8-positive cytotoxic T cell responses and contribute to slow progression of advanced melanoma.     

Diminished adhesion of Anaplasma phagocytophilum-infected neutrophils to endothelial cells is associated with reduced expression of leukocyte surface selectin

Anaplasma phagocytophilum propagates within neutrophils and causes a disease marked by inflammatory tissue injury or complicated by opportunistic infections. We hypothesized that infection with A. phagocytophilum modifies the binding of neutrophils to endothelial cells and the expression of neutrophil adhesion molecules and studied these changes in vitro. Infected dimethyl sulfoxide-differentiated HL-60 cells and neutrophils showed reduced binding to cultured brain and systemic endothelial cells and lost expression of P-selectin glycoprotein ligand 1 (PSGL-1, CD162) and L-selectin (CD62L) (to 33 and 5% of control values, respectively), at a time when the levels of beta(2) integrin and immunoglobulin superfamily adhesion molecules and activation markers Mac-1 and intercellular adhesion molecule 1 increased (5 to 10 times that of the control). The loss of CD162 and CD62L expression was inhibited by EDTA, which suggests that neutrophil activation and sheddase cleavage occurred. The loss of selectin expression and the retained viability of the neutrophils persisted for at least 18 h with A. phagocytophilum infection, whereas Escherichia coli and Staphylococcus aureus rapidly killed neutrophils. The adhesion defect might increase the numbers of infected cells and their persistence in the blood prior to tick bites. However, decreased CD162 expression and poor endothelial cell binding may partly explain impaired host defenses, while simultaneous neutrophil activation may aggravate inflammation. These observations may help us to understand the modified biological responses, host inflammation, and immune response that occur with A. phagocytophilum infections.