Free radicals and cardioplegia: the absence of an additive effect with allopurinol pretreatment and the use of antioxidant enzymes in the rat

The isolated perfused working rat heart model of cardiopulmonary bypass was used to assess whether (a) allopurinol pretreatment enhances resistance to normothermic (30 min) or hypothermic (4 h) ischemia; (b) addition of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) to cardioplegic and/or reperfusion solutions are protective; (c) any protective effects are additive. With normothermic ischemia, allopurinol pretreatment improved recovery of aortic flow from its control value of 25 +/- 3% to 48 +/- 6% (P less than 0.05). Similarly, SOD plus CAT used during both ischemia and reperfusion improved recovery of aortic flow from a control value of 28 +/- 4% to 48 +/- 6% (P less than 0.05). However, various combinations of the two types of intervention afforded no additive protection. Under hypothermic (21 degrees C) conditions, allopurinol pretreatment was not effective, whereas SOD and CAT added during ischemia and reperfusion improved recovery of aortic flow from its control value of 53 +/- 4% to 69 +/- 5% (P less than 0.05). This value was similar to allopurinol pretreatment and SOD plus CAT added during ischemia and reperfusion (69 +/- 6%: P less than 0.05). These results provide further evidence that reperfusion-induced free radical formation may adversely affect postischemic recovery of function. The absence of an additive effect suggests a common mechanism of action, which is likely to involve the free radical-generating enzyme xanthine oxidase; however, other mechanisms may exist. Our results further support the use of antifree radical intervention in conjunction with cardioplegia to protect the heart during ischemia and reperfusion.     

The 5-year results of a randomized trial of adjuvant radiation therapy after chemotherapy in breast cancer patients treated with mastectomy

The use of adjuvant radiation therapy in breast cancer patients treated with mastectomy and adjuvant chemotherapy has been controversial. In order to assess the necessity and effectiveness of adjuvant radiation therapy in this setting, we reviewed the results in 510 patients with T1-T3 tumors and pathologically positive nodes or tumors larger than 5 cm and negative nodes who were treated with adjuvant chemotherapy. Patients with four or more positive nodes or at least one positive apical node were randomized to receive either five or ten cycles of cyclophosphamide/Adriamycin (Adria Laboratories, Columbus, OH) (CA) and patients with one to three positive nodes or operable tumors larger than 5 cm and pathologically negative nodes were randomized to receive eight cycles of either cyclophosphamide, methotrexate, and 5-fluorouracil (5-FU) (CMF) or methotrexate and 5-FU (MF) chemotherapy. Two hundred six of these patients were subsequently rerandomized to receive either no further treatment or adjuvant radiotherapy. Thirty-five patients withdrew after randomization, including 34 who declined to receive radiotherapy. Radiation therapy consisted of 4,500 cGy in 5 weeks to the chest wall and appropriate draining lymph nodes. Median follow-up from chemotherapy randomization is 45 months for patients in the CA arm and 53 months for those in the CMF/MF arm. The crude rate of local failure (chest wall or draining lymph node areas) as first site of failure for patients randomized to receive chemotherapy only was 14%; for those randomized to receive both chemotherapy and radiotherapy it was 5% (P = .03). For patients in the CMF/MF arm, the rate of local failure as the first site of failure was nearly the same for patients randomized to chemotherapy only as for those randomized to adjuvant radiotherapy as well (5% v 2%). For patients in the CA arm, the crude rate of local failure was 20% for patients randomized to receive chemotherapy only, and 6% for those randomized to both types of adjuvant treatment (P = .03). Among the 43 patients treated with CA who actually received radiotherapy, there was only one local failure, compared with 12 local failures among the 59 patients (20%) who actually did not receive radiotherapy (P = .007). No significant difference was seen in disease-free survival or overall survival in either the CA or the CMF/MF arm between patients randomized to receive radiation therapy and those randomized to no further treatment.(ABSTRACT TRUNCATED AT 400 WORDS)     

Expulsive hemorrhage in cataract extraction

This article reports on six cases of massive expulsive hemorrhage during intracapsular cataract extraction (incidence = 0.17%). Some of the known risk factors are old age, hypertony, glaucoma, and an insufficient decrease in intraocular pressure following oculopression prior to surgery. Drainage of the suprachoroidal hemorrhage, closure of the wound and reformation of the anterior chamber are necessary surgical interventions. In one case the treated eye was saved and a visual acuity of 0.1 achieved.     

Urinary excretion of 5-oxoproline (pyroglutamic aciduria) as an index of glycine insufficiency in normal man

1. The evidence is accumulating to suggest that glycine, the simplest amino acid, is conditionally essential in man. Benzoic acid, by conjugation with glycine to form hippuric acid, is known to deplete the free glycine pool of the body. Glycine is one substrate for the enzyme glutathione synthase (EC 6.3.2.3) and in the inborn error of metabolism in which glutathione synthase function is defective, increased quantities of 5-oxoproline are excreted in the urine. 2. An oral dose of 4-10 g sodium benzoate was given to six normal adults to deplete the metabolic pool of glycine, and the urinary excretion of 5-oxoproline was followed for 6 h. In five of the six, a significant increase in the urinary 5-oxoproline was seen within 3 h. 3. These findings show that 5-oxoprolinuria can result from limited glycine availability, and may provide a useful test for assessing glycine sufficiency in a range of physiological and pathological states.     

Modulating effects of posttraining epinephrine on memory: Involvement of the amygdala noradrenergic system

These experiments examined the effects, on retention, of posttraining intra-amygdala administration of norepinephrine (NE), and propranolol. Rats were trained on a one-trial step-through inhibitory avoidance task and tested for retention 24 h later. Injections were administered bilaterally (1.0 microliter/injection) through chronically-implanted cannulae. Low doses of NE (0.1 or 0.3 microgram) administered shortly after training enhanced retention while higher doses (1.0 or 5.0 micrograms) were ineffective. Retention was not affected by NE administered 3 h after training. The effect of intra-amygdala NE on retention is blocked by simultaneous administration of propranolol (0.2 microgram). This finding suggests that the memory-enhancing effect of NE may be mediated by beta-receptors. Posttraining intra-amygdala NE also attenuated the retention deficit produced by adrenal demedullation. Further, intra-amygdala injections of propranolol (0.2 microgram) blocked the enhancing effect, on retention, of posttraining s.c. injections of epinephrine. These findings suggest that activation of noradrenergic receptors in the amygdala may be involved in memory processing and may play a role in the memory-modulating effect of peripheral epinephrine.     

Computed tomography findings in gastrointestinal involvement by opportunistic organisms in acquired immune deficiency syndrome

The computed tomography findings in two cases of gastrointestinal superinfection by opportunistic organisms in acquired immune deficiency syndrome are presented. Findings included thickening of the mucosal folds and the bowel wall in the small intestine and colon associated with cytomegalovirus and cryptosporidiosis. These cases indicate that it is important to look carefully at the gastrointestinal tract when performing computed tomography in this group of patients. Unsuspected bowel pathology may be demonstrated, or disease may be confirmed in clinically suspected cases.