Patterns of clinical metastasis in breast cancer: an analysis of 100 patients

Many patients diagnosed with breast cancer will develop metastases and these have diverse presentations. We have reviewed 100 consecutive patients who have died with metastatic breast cancer, to determine the frequency, sites and mode of presentation of recurrent disease. The commonest site of failure was loco-regional (n = 61), this usually presented with a mass, but a minority of patients also complained of pain. Bone metastases developed in 60 patients and produced bone pain, pathological fracture (n = 6) or cord compression (n = 5). Pulmonary metastases producing shortness of breath were diagnosed in 34 patients and were asymptomatic in a further 10. Intra-abdominal metastases were found at some time in 23 patients, most commonly in the liver (n = 20) and the majority complained of epigastric pain (n = 17). Brain metastases occurred in 23 patients and produced a wide range of symptoms including those of a space-occupying lesion (n = 10), cranial nerve palsy (n = 7), diabetes insipidus (n = 3), focal limb weakness (n = 2) and meningitis (n = 1). Three patients had choroid metastases producing reduced visual acuity. Recurrent breast carcinoma can present in a variety of ways, therefore any new symptom or sign should be considered to represent recurrence until proved otherwise.     

Congenitally cleft atrioventricular valves associated with secundum atrial septal defects

Three patients with the rare association of secundum ASD and congenital clefts of A-V valves are reported. These three patients illustrate the predictive valve of vectoracardiographic analysis in precisely determining the anatomic location of the valvular pathology. The embryologic origins of the lesion are briefly discussed. A review of the literature supports the use of vector analysis in the evaluation of the patients with this type of heart disease.     

The effect of alloy deformation on the average spacing parameters of nondeforming particles

It is shown on the basis of stereological definitions and a few simple experiments that the commonly used average dispersion parameters, area fraction (A _A )_β, areal particle densityN _Aβ and mean free path λ_α, remain invariant during plastic deformation in the case of nondeforming equiaxed particles. Directional effects on the spacing parametersN _Aβ and λ_α arise during uniaxial deformation by rotation and preferred orientation of non-equiaxed particles. Particle arrangement in stringered or layered structures and the effect of deformation on nearest neighbor distances of particles and voids are briefly discussed in relation to strength and fracture theories. Formerly with the Division of Engineering, Brown University, Providence, RI     

The in vitro radiosensitivity of human head and neck cancers

A study was made of the intrinsic radiosensitivity of 140 biopsy and surgical specimens of malignant head and neck tumours of different histologies. Using a soft-agar clonogenic assay, the material was assessed for the ability to grow in culture (colony-forming efficiency; CFE) and inherent tumour radiosensitivity (surviving fraction at 2 Gy, SF2). The success rate for obtaining growth was 74% (104/140) with a mean CFE of 0.093% (median 0.031) and a range of 0.002-1.3%. SF2 was obtained for 88 of 140 specimens, representing a success rate of 63% with a mean SF2 of 0.48 (median 0.43) and a range of 0.10-1.00. There were no significant differences in radiosensitivity between different sites of the head and neck region. There were no significant relationships between SF2 and disease stage, nodal status, tumour grade, patient age, primary tumour growth pattern and CFE. The results were compared with those for other tumour types previously analysed with the same assay. The distribution of the SF2 values for the head and neck tumours was similar to that for 145 cervix carcinomas and there was no significant difference in mean radiosensitivity between the two tumour types. Also, there was no significant difference in radiosensitivity between head and neck tumours and either breast or colorectal cancers. However, a group of eight lymphomas was significantly more radiosensitive. These results confirm the feasibility of carrying out radiosensitivity measurements using a soft-agar clonogenic assay on head and neck tumours. In addition, the work has shown that radiosensitivity is independent of many clinical parameters and that the mean value is similar to that reported for cervix carcinomas.     

Persistent membrane translocation of protein kinase C alpha during 12-0-tetradecanoylphorbol-13-acetate-induced apoptosis of LNCaP human prostate cancer cells

Others have reported that the phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA), an activator and down-regulator of most protein kinase C (PKC) isozymes, can induce apoptotic cell death of androgen-sensitive LNCaP but not androgen-insensitive PC-3 or DU 145 human prostate cancer cells. As a first step toward uncovering the mechanism by which TPA induces apoptosis of LNCaP cells, we quantified expression of PKC isozyme mRNAs in unmodified and TPA-resistant LNCaP cells and in naturally TPA-resistant PC-3, PC-3M, and DU 145 cells. All of the cell lines and normal prostate expressed RNAs for PKC alpha, delta, epsilon, eta, and mu; only DU 145 cells and normal prostate expressed PKC beta and theta RNAs, and none expressed PKC gamma. The amount of PKC alpha RNA and protein was 6- to 38-fold lower, and PKC mu RNA was 4.5- to 16.5-fold higher in unmodified and TPA-resistant LNCaP cells than in the androgen-independent cells. We examined the effects of TPA on PKC alpha and mu mRNA levels and on membrane translocation of PKC alpha. Incubation with TPA for 6 h or more induced 95% inhibition of cell growth, a transient 12-fold increase and 5-fold decrease in PKC alpha and mu mRNA levels, respectively, and prolonged translocation of PKC alpha to non-nuclear membranes in unmodified LNCaP cells and in TPA-resistant LNCaP cells from which TPA had been removed for 10 days. TPA-resistant LNCaP cells in the continuous presence of TPA, or 24 h after removal of TPA, had down-regulated PKC alpha and remained resistant to re-addition of TPA. These data demonstrate a strong correlation of the presence and absence of membrane PKC alpha with apoptosis and resistance to apoptosis, respectively.     

Effect of nitrogen dioxide and other combustion products on asthmatic subjects in a home-like environment

Nitrogen dioxide (NO2) is one of a number of nitrogen compounds that are by-products of combustion and occur in domestic environments following the use of gas or other fuels for heating and cooking. In this study, we examined the effect of two levels of NO2 on symptoms, lung function and airway hyperresponsiveness (AHR) in asthmatic adults and children. In addition, in the same subjects, we examined the effects of the same levels of NO2 mixed with combustion by-products from a gas space heater. The subjects were nine adults, aged 19-65 yrs, and 11 children, aged 7-15 yrs, with diagnosed asthma which was severe enough to require daily medication. All subjects had demonstrable AHR to histamine. Exposures were for 1 h on five separate occasions, 1 week apart, to: 1) ambient air, drawn from outside the building; 2) 0.3 parts per million (ppm) NO2 in ambient air; 3) 0.6 ppm NO2 in ambient air; 4) ambient air+combustion by-products+NO2 to give a total of 0.3 ppm; and 5) ambient air+combustion by-products+NO2 to give a total of 0.6 ppm. Effects were measured as changes in lung function and symptoms during and 1 h after exposure, in AHR 1 h and 1 week after exposure, and in lung function and symptoms during the week following exposure. Exposure to NO2 either in ambient air or mixed with combustion by-products from a gas heater, had no significant effect on symptoms or lung function in adults or in children. There was a small, but statistically significant, increase in AHR after exposure to 0.6 ppm NO2 in ambient air. However, there was no effect of 0.6 ppm NO2 on AHR when the combustion by-products were included in the test atmosphere nor of 0.3 ppm NO2 under either exposure condition. We conclude that a 1 h exposure to 0.3 or 0.6 ppm NO2 has no clinically important effect on the airways of asthmatic adults or children, but that 0.6 ppm may cause a slight increase in airway hyperresponsiveness.