Carbonic anhydrase (CA IX) expression, a potential new intrinsic marker of hypoxia: correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix.

There is increasing evidence that hypoxia-regulated gene expression influences tumor aggressiveness, contributing to the poorer outcome of patients with hypoxic tumors. The role of the transcriptional complex hypoxia-inducible factor-1 as an important mediator of hypoxia-regulated gene expression is one of the best documented pathways. Recently, it has emerged that certain tumor-associated carbonic anhydrases (CAs) can be added to the list of known hypoxia-inducible factor-responsive genes. Here we show that the immunohistochemical expression of the tumor-associated CA IX is correlated with the level of hypoxia in human cervical tumors. We performed a prospective study in 68 patients where needle electrodes were used to make direct measurements of tumor oxygenation levels. CA IX expression was evaluated immunohistochemically in pretreatment tumor biopsies. There was a significant positive correlation between the level of tumor hypoxia (HP5) and the extent of CA IX expression. A retrospective study of 130 squamous cell cervical carcinomas demonstrated that a semiquantitative immunohistochemical analysis of CA IX expression in tumor biopsies is a significant and independent prognostic indicator of overall survival and metastasis-free survival after radiation therapy. These studies provide clinical evidence that CA IX expression is up-regulated in hypoxic human cervical tumors and is associated with a poor prognosis. CA IX may act as an intrinsic marker of tumor hypoxia and poor outcome after radiation therapy. The level of CA IX expression may be used to aid in the selection of patients who would benefit most from hypoxia-modification therapies or bio-reductive drugs.

New concepts of digitalis.

The data presented in this review have substantiated the following ideas:* There is a direct relationship between digitalis dosage and myocardial contractile force. A small dose of digitalis produces a small increase of the contractile force of the heart and a large dose increases the force of the heart's contraction by a much greater amount, whether the heart is normal, has a poor reserve, or is in frank failure.* Digitalis is of benefit to the patient with cardiovascular disease whether his heart is in failure or not.

Experimental pulmonary air embolism in dogs.

Air infused into the jugular vein of dogs at a constant rate for one hour produced transient hypotension, modest elevation of the systemic venous pressure and a considerable fall of the arterial oxygen tension. All of these measurements returned almost to normal on the termination of the infusion. A lethal rate of infusion, 0.69 ml of air per kg of body weight per minute, produced heart failure with a decided rise of systemic venous pressure and fall of blood pressure. The pre-failure oxygen pressure did not fall to a lethal level. Six and a half minutes was the longest time that the characteristic murmur could be heard after the cessation of infusion of non-fatal doses of air.