Novel applications of therapeutic hypothermia: report of three cases

Therapeutic hypothermia can provide neuroprotection in various situations where global or focal neurological injury has occurred. Hypothermia has been shown to be effective in a large number of animal experiments. In clinical trials, hypothermia has been used in patients with postanoxic injury following cardiopulmonary resuscitation, in traumatic brain injury with high intracranial pressure, in the perioperative setting during various surgical procedures and for various other indications. There is thus evidence that hypothermia can be effective in various situations of neurological injury, although a number of questions remain unanswered. We describe three patients with unusual causes of neurological injury, whose clinical situation was in fundamental aspects analogous to conditions where hypothermia has been shown to be effective.     

Orotic Acid Improves Recovery of Left Ventricular Function Days After Heterotopic Transplantation

The preclinical evidence for a potential influence of calcium channel blockers (CCBs) on carcinogenesis is discussed in the light of a broad database from rodent carcinogenicity studies as well as literature data. In all bioassays performed in rats and mice on the dihydropyridine CCBs — nifedipine, nimodipine, nisoldipine, and nitrendipine — no evidence was found for a carcinogenic potential of these compounds. Calcium is an essential intracellular signal for cell proliferation and apoptosis. The crucial role of increased cell proliferation in all stages of carcinogenesis is well documented. Some indirect experimental evidence also points to a role of defective apoptosis in tumor promotion. CCBs uniformly inhibit cell proliferation, whereas the influence of CCBs on apoptosis is inconsistent, resulting in an inhibition or increase in apoptosis dependent on cell type. Accordingly, antitumorigenic effects of CCBs have been reported based on their antiproliferative action. A tumor-promoting effect of CCBs based on inhibition of apoptosis, however, remains purely speculative and, in fact, can be denied based on the results of in vivo bioassays. It is therefore concluded that there is no preclinical evidence that should give rise to concern over the carcinogenic potential of dihydropyridine-type CCBs.     

Assessing the hypothalamo-pituitary-adrenocortical axis using physiological doses of adrenocorticotropic hormone

We compared cortisol responses to 1 microgram adrenocorticotropic hormone (ACTH), 250 micrograms ACTH and insulin-induced hypoglycaemia (IIH), in patients suspected to have secondary hypocortisolism. Twenty- four patients (16 with hypothalamopituitary disorders and 8 on long- term glucocorticoid therapy) and eight healthy controls, underwent all three test protocols, with intervals of one day between each test. Mean cortisol responses to all three tests were comparable in both groups, but were more closely correlated for IIH vs. the 1 microgram ACTH test (r = 0.96) than for IIH vs. the 250 micrograms ACTH test (r = 0.88). Seven patients had discrepant results; all had a normal peak cortisol response to 250 micrograms ACTH (> 550 nmol/l), but a subnormal response to 1 microgram ACTH. Six of these also had a subnormal response to IIH. Cortisol responses to IIH match more closely those for 1 microgram ACTH in individual instances than those for 250 micrograms ACTH. The standard 250 micrograms ACTH stimulation, being supraphysiological, leads to underdiagnosis of the hypocortisolaemic state. The 1 microgram ACTH stimulation test should replace the standard 250 micrograms ACTH stimulation test in assessing the hypothalamo-pituitary-adrenocortical axis in secondary hypocortisolism.      

Daily enteral feeding practice on the ICU: attainment of goals and interfering factors

Background

The purpose of this study was to evaluate the daily feeding practice of enterally fed patients in an intensive care unit (ICU) and to study the impact of preset factors in reaching predefined optimal nutritional goals.

Methods

The feeding practice of all ICU patients receiving enteral nutrition for at least 48 hours was recorded during a 1-year period. Actual intake was expressed as the percentage of the prescribed volume of formula (a success is defined as 90% or more). Prescribed volume (optimal intake) was guided by protocol but adjusted to individual patient conditions by the intensivist. The potential barriers to the success of feeding were assessed by multivariate analysis.

Results

Four-hundred-and-three eligible patients had a total of 3,526 records of feeding days. The desired intake was successful in 52% (1,842 of 3,526) of feeding days. The percentage of successful feeding days increased from 39% (124 of 316) on day 1 to 51% (112 of 218) on day 5. Average ideal protein intake was 54% (95% confidence interval (CI) 52 to 55), energy intake was 66% (95% CI 65 to 68) and volume 75% (95% CI 74 to 76). Factors impeding successful nutrition were the use of the feeding tube to deliver contrast, the need for prokinetic drugs, a high Therapeutic Intervention Score System category and elective admissions.

Conclusion

The records revealed an unsatisfactory feeding process. A better use of relative successful volume intake, namely increasing the energy and protein density, could enhance the nutritional yield. Factors such as an improper use of tubes and feeding intolerance were related to failure. Meticulous recording of intake and interfering factors helps to uncover inadequacies in ICU feeding practice.

     

Phytohemagglutinin-stimulated normal human peripheral blood lymphocytes in folate-depleted medium: an in vitro model for megaloblastic hemopoiesis

Normal human peripheral blood lymphocytes cultured with phytohemagglutinin in folate-free RPMI 1640 medium supplemented with normal human serum exhibit megaloblastic maturation. These changes are accompanied by a decrease in intracellular folate content, and when compared to folate-replete cells, reveal increased 3H-thymidine incorporation into DNA together with a decreased inhibitory effect of deoxyuridine on 3H-thymidine incorporation. This in vitro system of cellular folate deficiency is a convenient model for analysis of biochemical events accompanying megaloblastic maturation.