Breast cancer in women under 30 years of age

Summary Conflicting opinions exist concerning clinical and pathological presentation, as well as evolution and prognosis, of breast cancer in young women. The roles of associated pregnancy and lactation on these parameters is also unclear. These two conditions are studied in the present work through the comparison of two breast cancer patient age groups: patients under the age of 30 (Group A) and premenopausal patients aged 45–49 (Group B).Rapidly growing and/or inflammatory breast cancer (rapidly progressing breast cancer: RPBC) — a special form of Breast Cancer with a poor prognosis very frequent in the Tunisian breast cancer population — was more often present among Group A patients. This difference is a consequence of the more frequent association of this breast cancer group with pregnancy or lactation; nearly all the cases of breast cancer associated with pregnancy or lactation are RPBC. For breast cancer without the pregnancy/lactation association, the younger group generally shows poorer histological grading and more severe evolution.The number of patients in our study is not really sufficient to allow statistically significant conclusions, but it does seem clear that young age and associated pregnancy/lactation are aggravating factors in Tunisian breast cancer patients.     

Gout and hyperlipidaemia. Effect of overweight on the levels of circulating lipids

A study of the serum lipids in 90 patients with gout and 90 controls matched for age and weight index demonstrated that in gout there was a significant elevation of the mean serum levels of cholesterol (282 +/- 55 mg/100 ml), triglycerides (183 +/- 161 mg/100 ml) and phospholipids (270 +/- 61 mg/100 ml) compared with the controls whose mean values were respectively 243 +/- 41 mg, 95 +/- 53 mg and 245 +/- 36 mg. Hyperlipidaemia of mixed type was the most common lipid defect in the patients with gout; there was no difference in the frequency of pure hypercholesterolaemia (without hypertriglyceridaemia) between gout and the controls. The frequency of anomalies of blood lipid levels in gout does not result from (or not solely from) obesity since patients with gout and controls were matched for their weight and height. There was a correlation between the serum lipid levels and obesity in the controls but this was not demonstrable in the patients with gout.     

Kinetic properties of the sodium current in striated muscle fibres on the basis of the Hodgkin—Huxley theory

1. The kinetic properties of the sodium current in skeletal muscle fibre, obtained from records in a double sucrose-gap apparatus, have been analysed in terms of the Hodgkin—Huxley formulation by means of a curve fitting computer program.

2. The net sodium currents were obtained by subtracting records in Ringer and Ringer tetrodotoxin; the currents are inward for depolarizations V from +25 to +128 mV (V_Na). The I_Na—V characteristic shows a small inward rectification for V > + 128 mV.

3. The characteristics of both sodium conductance and permeability are described.

4. The activation and inactivation parameters, m and h, are calculated and compared with those experimentally established in a previous work (Ildefonse & Rougier, 1972) and with the results of Adrian, Chandler & Hodgkin (1970).

5. The currents calculated with these parameter values fit rather well with the experimental ones, the permeability approach being slightly better.

6. The main difference between the experimental and calculated curves is the slower inactivation of the calculated current at V = +55 mV; this difference is envisaged as a possible consequence of some activity in the tubular system of the muscle fibre.

     

Effects of chronic torbafylline treatment on energy metabolism of ischemic skeletal muscle

This study investigates the effects of chronic oral treatment with Torbafylline, a xanthine derivative, on the energy metabolism of chronically ischemic skeletal muscle of the rat. Blood flow to one hindlimb was reduced by unilateral femoral artery ligation. One group of animals received 5 ml/kg body weight saline while the other group received 25 mg/kg Torbafylline dissolved in the same volume of saline. Treatment was pursued for 5 weeks, 2 times a day, except during the weekends. In NaCI-treated rats, ischemia leads to muscle atrophy as measured by a decrease in muscle weights and to a concomitant decrease in lactate dehydrogenase and creatine kinase activities, while adenine nucleotide contents remain unchanged. Chronic administration of Torbafyllin almost totally prevented these changes. In isolated mitochondria from ischemic and non-ischemic muscles, treated or not with Torbafylline, no significant changes were measured in malate dehydrogenase, citrate synthase, creatine kinase, cytochrome oxidase and oligomycin-sensitive ATPase. However, in mitochondria prepared from NaCI-treated muscles with limited flow, an increase of substrate oxidation was observed after formation of endogenous ATP (final state 4 of oxidation). This increase can be interpreted as an indication of a deviation from the normal use of ATP, e.g., non-efficient energy production. Torbafylline treatment prevented this apparent waste of energy.     

Pulmonary sequestration (author's transl)

Pulmonary sequestration is a relatively rare condition in which a part of lung tissue has no or only a secondary connection with the tracheobronchial tree. Blood supply comes from the aorta in anomalous branches. Sequestrations may be intra- or extralobar. Gerle et al. include both types in the general term congenital bronchopulmonary foregut malformation. Two surgically confirmed observations of bilateral intralobar pulmonary sequestrations are reported. The clinical features are recurrent respiratory infections with cough, fever and purulent sputum. X-rays only show nonspecific alterations. Chronic changes in the lower lobes should draw attention to pulmonary sequestration. Thoracic aortography is the procedure of choice in establishing the diagnosis and should always be carried out preoperatively. Segmental resection or lobectomy is the indicated treatment.     

Evolution of fibrinogen levels in rat fetal and maternal blood during gestation

Plasma fibrinogen levels increase during the last third of gestation in the pregnant rat. In the fetus, they are barely measurable at 18 days, increase rapidly thereafter and reach adult values just before birth, in a matter of 3 days.     

Gemcitabine aerosol: in vitro antitumor activity and deposition imaging for preclinical safety assessment in baboons

Aim: To characterize gemcitabine aerosol, its in vitro activity against lung cancer cells, its deposition, and tolerance in a non-human primate model. Methods: In vitro cytotoxicity of nebulized gemcitabine against NCI-H460 and A549 lung cancer cells was tested using a growth inhibition assay and compared with non-nebulized gemcitabine. The ^99mTc-DTPA-radiolabeled gemcitabine aerosol was characterized by cascade impaction and the gemcitabine mass/^99mTc activity relationship was established for further quantitative nuclear imaging. Nine weekly inhalations at a target dose of 1 mg/kg body weight of gemcitabine were performed in three baboons using dynamic scintigraphic acquisitions for continuous monitoring of gemcitabine delivery during inhalation. Gemcitabine plasma concentrations were measured during the first inhalation. Results: Growth inhibition assays for both NCI-H460 and A549 cells did not differ between nebulized and non-nebulized gemcitabine. Aerosol characterization showed a particle mass median aerodynamic diameter of 3.7±0.8 μm and a linear relationship between gemcitabine mass (y) and ^99mTc activity (x) (y=0.82x − 10⁻⁵, R ²=0.88). No toxicity was observed after nine weekly inhalations of a mean dose of gemcitabine of 11.1 mg (88% of the target dose) as assessed from scintigraphic data. A dose-dependent peak plasma concentration of gemcitabine (20–74 ng/ml) was observed by the tenth minute of inhalation. Conclusions: We have characterized a gemcitabine aerosol suitable for intrathoracic airway deposition and demonstrated that jet nebulization does not alter the cytotoxic properties of the drug. In a primate model, we have developed a scintigraphic procedure for the monitoring of aerosol deposition, and we have demonstrated the safety of nine weekly aerosol administrations of gemcitabine.Research supports: This study was supported by a grant from the Comité Départemental du Maine-et-Loire de la Ligue Nationale Contre le Cancer.     

Benign Epithelial Ovarian Tumours—cancer Precursors or Markers for Ovarian Cancer Risk?

The natural history of the development of epithelial ovarian cancer remains obscure and no effective screening test exists. In several human malignancies progression from benign to invasive tumour occurs, but this sequence has not been established for epithelial ovarian cancer. We have reviewed epidemiological, histopathological and molecular studies of benign epithelial ovarian tumours to assess the evidence for and against such a progression in ovarian cancer. These data suggest that a diagnosis of a benign ovarian cyst or tumour is associated with an increased risk of ovarian cancer later in life. Current evidence also suggests that benign serous tumours can progress to low-grade serous cancer and that benign mucinous tumours can progress to mucinous cancer. The more common high-grade serous ovarian cancers are likely to arise de novo.