In remembrance of Eugene Ladislas Kanabrocki (18 April 1922 * 23 April 2009): a 'General' in the battle of penetrating the normal range and in revealing its relation to the cosmos.

Col. Eugene L. (Gene) Kanabrocki, PhD, commanding officer of the 361st Medical Laboratory of the U.S. Army Reserve, together with Col. Lawrence E. (Larry) Scheving, Professor at the University of Arkansas, initiated in May 1969 a linked cross-sectional (hybrid) study at Fort Sam Houston, TX, to examine the oscillatory (circadian) nature of many physiological variables in a group of 13 army men, 22-28 years of age, anticipating that such data would serve, as indeed they did, as time-specified reference values in future investigations of health and aging. In the initial study, 36 variables were examined around the clock in observations at 3-hour intervals. In subsequent 24-hour profiles, mapped in May of 1971 (mostly on new, young subjects, and not officially part of the Aging Project), 1979, 1988, 1993, 1998 and 2003, additional subjects and variables were included. The follow-up studies were conducted at the Hines VA Medical Center in Hines, Illinois. Of the original 13 subjects, four were measured in all 6 studies and another four in 5 of the 6 studies. Three of the eight became diabetic (Type II) and three had vascular circulatory problems. Presently, a bank of circadian data for 187 medically relevant variables of blood (plasma or serum), saliva, urine, vital signs and other variables on the same subjects covers a span of 34 years. Dr. Robert B. Sothern (RBS), of the University of Minnesota, USA, the major analyst of Gene's investigations, in addition to being an add-on subject as he was in three studies, set up the half-hourly monitoring of blood pressure (BP) and heart rate (HR) in the 2003 study that yielded the data suggesting that the standard deviations (SD) of systolic (S) and diastolic (D) BP and HR are infl uenced by a magnetic storm. Since the standard deviation rather than the amplitude of a vascular spectral component was affected, we may be dealing with a stochastic rather than frequency window-dependent resonance with a magnetic storm. Gene and RBS also found (p< 0.08) an about-decadal signature of solar activity in long-acting natriuretic peptide (LANP), vessel dilator (VSDL), insulin, LH, prolactin, T3 uptake and, most importantly, in melatonin (p=0.004), noted solely to constitute a stimulus for follow-up studies, even when resonance occurs in an anticipated Horrebow-Schwabe circadecadal window gauged by relative sunspot (Wolf) numbers and involves many endocrine variables, as anticipated on the basis of independent evidence in melatonin and cortisol. The wealth of circadian information collected in these studies by Gene constitutes a treasure trove of unique advances in the battle of the normal range, with solid contributions also by Prof. Germaine Cornélissen of the University of Minnesota, USA, and by Prof. Ramon C. Hermida of the University of Vigo, Spain.

The ratio of observed-to-expected mortality as a quality of care indicator in non-surgical VA patients.

This study attempts to validate the use of the observed-to-expected (O/E) mortality ratio as an indicator of quality of care. The primary objective is to determine whether medical records of 111 patients who died in Veterans Affairs (VA) hospitals with high overall ratios of observed-to-expected mortality rates show greater evidence that life might have been meaningfully prolonged with more expert care than the records of matched patients who died in VA hospitals with low O/E ratios. Patient matching criteria included: age, diagnosis responsible for length of stay, type of VA hospital, and the mortality probability predicted by logistic regression. Expert physicians blindly and independently reviewed pairs of medical records, assessing comparative care on a symmetrical, nine-alternative visual analog scale. A slight shift in distribution toward better care in low-ratio hospitals was not statistically significant. Results of an additional analysis, not dependent on pairing, showed that preventability of death is more strongly related to physicians' estimates of mortality risk at admission, whether transferred from a nursing home, do-not-resuscitate status, and accuracy of discharge coding than to VA Medical Center O/E ratios.

Predictors of blinding or serious eye injury in blunt trauma.

Multivariate analysis was used to identify factors predicting injury and visual outcome in 94 blunt trauma patients evaluated for eye injuries among 6700 admissions to a level I trauma center over a 29-month period. Patients with penetrating eye injuries were excluded from this review. Eye injury was detected in 93% or 87 of the patients evaluated. Seven percent of eye injuries resulted in blindness, 22% were serious (visual acuity between 20/40 and 20/200 or eye injury requiring surgery), and 71% were temporary (final visual acuity of 20/40 or better). The presence of an afferent pupillary defect or a nonreactive pupil was the most important factor in predicting the severity of eye injury (p = 0.0023), followed by facial fractures (p = 0.0084), and no eye opening or eye opening to pain within the Glasgow Coma Scale (p = 0.02). Eye injury is an infrequent complication of blunt trauma. Appropriate consultation for evaluation of this problem can be obtained based on findings from the initial history and screening physical examination.

Relationship between in vitro and in vivo radiosensitivity of lymphocytes in chronic lymphocytic leukemia.

A significant positive correlation was obtained between the in vitro radiosensitivity of the blood lymphocytes of patients with chronic lymphocytic leukemia (CLL) and the in vivo response of the total leukocyte count subsequent to radiation therapy. Four types of equations were used to represent and measure the effect of in vitro X-irradiation on lymphocytes from CLL patients and measure the response of patients to a course of radiotherapy. For the in vivo analysis we used data from 10 patients who were routinely treated with a total of 16 courses of radiation therapy. The total leukocyte count showed a uniform exponential decline during a course of therapy. According to the literature, about 25% of all CLL patients and about 50% of CLL patients with advanced disease are resistant to chemotherapy. The equations and indices of the present study may be useful to diagnose CLL patients who are prone to be resistant to chemotherapy.

National Cooperative Crohn's Disease Study: study design and conduct of the study.

The design and execution of the National Cooperative Crohn's Disease Study are described in this paper. The Study incorporated several noteworthy features developed to meet specific demands of the disease and its therapy. A standard clinical grading system, the Crohn's Disease Activity Index (CDAI) was developed to allow uniform decentralized clinical evaluation and decision-making throughout the 5 yr of the study. All three drugs in widespread clinical use in Crohn's disease were studied both for suppressive and prophylactic efficacy and for toxicity. The study employed a scheme for double-blind evaluation of patient progress which allowed adjustment of prednisone dose according to the degree of illness and ensured continuous monitoring for serious toxicity of any study drug. Results were analyzed primarily by ranking the clinical outcome of every patient according to a uniform and detailed scheme and applying Wilcoxon nonparametric statistics. Outcome was also analyzed by life-table methods. Eleven hundred nineteen patients were entered and 604 patients were randomized at 14 study centers during the 5-yr duration of the study. Twenty patients were eliminated from analysis as not meeting diagnostic criteria for Crohn's disease, and another 15 patients were eliminated as not meeting other preestablished criteria for analysis. Nine percent of randomized patients, equally distributed in the four treatment groups, withdrew as noncompliant. Ninety percent of patients completed all or all but one protocol-specified visits, and 95% completed the final radiologic and sigmoidoscopic evaluation.

National Cooperative Crohn's Disease Study: results of drug treatment.

The response of active and quiescent Crohn's disease to prednisone, sulfasalazine, or azathioprine has been studied in 569 patients in a placebo-controlled, randomized, multicenter cooperative trial. The response of active symptomatic disease to prednisone or sulfasalazine was significantly better than to placebo. Response to azathioprine was better than to placebo, but the difference did not reach conventional levels of statistical significance. Patients with colonic involvement were especially responsive to sulfasalazine, and those with small bowel involvement were especially responsive to prednisone. Patients' drug therapy immediately before entry to the study significantly affected subsequent response. For patients with quiescent disease, none of the drugs was superior to placebo in prophylaxis against flare-up or recurrence. There is less than a 5% risk that a clinically significant prophylactic effect of any of the drug regimens was missed.

A trial of sulfasalazine as adjunctive therapy in Crohn's disease.

The effect of the combination of sulfasalazine and prednisone has been compared with that of prednisone and placebo in 89 actively symptomatic patients with Crohn's disease in a double-blind, randomized, multicenter controlled trial. The combination was less effective than prednisone alone in treatment of active symptomatic disease. The probability of obtaining this result, if sulfasalazine truly has a clinically useful effect equal to or greater than that specified in the calculation, is less than 1%. Patients who were in remission at the end of 8 wk were rerandomized to receive either the two drugs together or prednisone plus placebo while repeated systematic attempts to withdraw prednisone were made over the next 6 mo. Sulfasalazine showed no prednisone-sparing effect as judged either by outcome ranking or total dose of prednisone consmed by the two treatment groups. However, in this comparison the probability is greater than 5% that, given the results observed, a clinically useful effect of sulfasalazine of specified minimum degree truly exists. It was possible to withdraw prednisone from 25% of patients at the first attempt and ultimately in 37%.

Rederived values of the eight coefficients of the Crohn's Disease Activity Index (CDAI).

A previous paper reported derivation of the Crohn's Disease Activity Index (CDAI) from data on 112 patients. We have now rederived the values of the eight coefficients of the CDAI using data from 1058 visits of patients enrolled in the National Cooperative Crohn's Disease Study and the Trial of Adjunctive Sulfasalazine in Crohn's Disease. The rederived coefficients are similar to the original ones. New and original index values calculated on the same data from patient visits correlated very highly. Because there is so little difference between the original and the rederived versions, continued use of the original version is suggested in order to maintain comparability of new studies employing this tool with those previously accomplished.

Clinical implications of sickle-cell trait and glucose-6-phosphate dehydrogenase deficiency in hospitalized black male patients.

To determine whether sickle-cell trait and glucose-6-phosphate dehydrogenase deficiency influence the course and fatality rates of certain diseases requiring hospitalization, especially those associated with thrombotic phenomena, we conducted a co-operative study of 65,154 consecutively admitted, black male patients in 13 Veterans Administration hospitals. The overall frequency of sickle-cell trait was 7.8 per cent and of glucose-6-phosphate dehydrogenase dificiency 11.2 per cent. Both conditions were present in 0.9 per cent of those examined. There were regional, but no age-dependent, differences in the frequency of sickle-cell trait. Sickle-cell trait had no effect on average age at hospitalization or death, overall mortality, length of hospitalization on medical and surgical wards and frequency of any diagnosis, except essential hematuria and pulmonary embolism. Although statistically significant (P less than 0.001), the differences for the latter were small (1.5 per cent of all patients with normal hemoglobin and 2.2 per cent of patients with sickle-cell trait). Glucose-6-phosphate dehydrogenase deficiency had no adverse effect.

Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study.

Needing a single index of degree of illness in Crohn's disease, the National Cooperative Crohn's Disease Study group collected data prospectively from 187 visits of 112 patients with Crohn's disease of the small bowel, colon, or both. Information on 18 predictor variables was gathered at each visit. In addition, the attending physician rated his over-all evaluation of how well the patient was doing and compared the patient's status with that at the previous visit. A multiple regression computer program was utilized to derive an equation for prediction of the physician's over-all ratings from a subset of the predictor variables fulfilling a combination of constraints. This equation, numerically simplified and utilizing eight selected variables, is the Crohn's Disease Activity Index. Index values of 150 and below are associated with quiescent disease; values above that indicate active disease, and values above 450 are seen with extremely severe disease.