Hyperoxia decreases cutaneous blood flow in high-perfusion areas.

The mechanism by which hyperoxia decreases blood flow is still not understood. Hyperoxemia-induced vasoconstriction is known to occur in many organs, including brain and retina, skeletal muscle, and myocardium. Whether this also occurs in skin is unknown. This study was conducted in healthy volunteers exposed intermittently to 100% oxygen (F(I)O(2) 1.0). Perfusion of forearm skin was measured by laser Doppler imaging (LDI). In series 1, it was measured in 7 subjects before, during, and after 15 min of oxygen breathing. In series 2, flow was measured, also during air and O(2) breathing, after perfusion was raised by (a) sympathetic blockade (induced by a topically applied local anesthetic) (n=9) and by (b) current-induced vasodilation (n=8). In normal unperturbed skin, there was no significant change with hyperoxia. When basal perfusion was raised by topical anesthesia or by current, there was also no change in mean perfusion overall with hyperoxia. However, areas with the highest perfusion (upper decile) showed a significant perfusion decrement with hyperoxia (-30% and -20%, respectively; p<0.001). Vasoconstriction with hyperoxia has been demonstrated in human skin. The fact that it is observed only when flow is increased above basal levels and then only in high-flow vessels suggests that cutaneous blood flow control is primarily regulated by variables other than oxygen.

Fludarabine and cytarabine as a sequential infusion regimen for treatment of adults with recurrent, refractory or poor prognosis acute leukemia.

We did a retrospective analysis on the safety and efficacy of sequential infusion fludarabine and cytosine arabinoside (ara-C) in treating refractory, recurrent or poor prognosis acute leukemia in adult patients. Forty-five adult patients with acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL) received a total of 68 courses of sequential continuous infusion of fludarabine for 2 days (total dose 71.5 mg/m(2) ) followed by 3 days of ara-C (total dose 7590 mg/m(2) ). Thirty-nine patients had refractory or recurrent disease, and six had other adverse prognostic features. Thirty-six patients had AML, seven had ALL, and two had CML in blastic phase. Complete remission was seen in 20 patients (44%), and partial remission in 5 patients (11%), giving a total response rate of 56%, similar for both AML and ALL. Duration of response to prior therapy did not affect the response rate. All 3 patients with Philadelphia chromosome positive ALL obtained complete remission. Median remission duration was 4.7 months (range 0.6-36.6), and median overall survival was 5.0 months (0.7-40+). Median overall survival was 10.1 months in responders. Pulmonary toxicity was seen in 8 patients, of whom 2 died from adult respiratory distress syndrome. No cardiac toxicity was observed, but 3 patients had transient cerebellar toxicity. Profound myelosuppression was seen in all patients. We conclude that the sequential infusion of fludarabine and ara-C is an effective non-cardiotoxic regimen for adults with refractory, recurrent or poor prognosis acute leukemia, may be particularly useful for resistant Philadelphia chromosome positive ALL, and may warrant further investigation in this subset. Pulmonary rather than neurological toxicity may be a unique side effect of the regimen.

The epidermal growth factor receptor is required to maintain the proliferative population in the basal compartment of epidermal tumors.

Previous studies using keratinocytes from epidermal growth factor receptor (EGFR)-deficient mice revealed that the EGFR is not required for papilloma formation initiated by a mutant rasHa gene, although the tumors that develop are very small (A. A. Dlugosz et aL, Cancer Res., 57: 3180-3188, 1997). The current study used a combination of bromodeoxyuridine pulse-chase, proliferating cell nuclear antigen distribution, and differentiation marker analysis to reveal the following: (a) the EGFR was required to maintain the proliferative population in the basal cell compartment of papillomas; (b) in the absence of EGFR, cycling tumor cells migrated into the suprabasal compartment and initiated the differentiation program prematurely; and (c) these changes were associated with cell cycle arrest. Further analysis of v-rasHa-transformed EGFR-deficient keratinocytes in vitro indicated that such cells migrated more on and attached less to extracellular matrix components. Together, these studies reveal that an essential function for the EGFR pathway in squamous tumors is to maintain a proliferative pool of basal cells and prevent premature terminal differentiation.

Severe cold agglutinin disease and cryoglobulinemia secondary to a monoclonal anti-Pr2 IgM lambda cryoagglutinin.

OBJECTIVE: To present a case of cold agglutinin disease/cryoglobulinemia secondary to a monoclonal anti-Pr2 IgM lambda antibody, and review the literature on the occurrence of this antibody in cold-induced disease and the clinical disease associated with it. METHODS: Cryoantibody characteristics were evaluated by cold precipitation. The antigen specificity of the monoclonal IgM lambda antibody was evaluated using techniques of selective red blood cell absorption. RESULTS: In our patient, we were able to identify an antibody with both cryoglobulinemic and cold agglutinin (cryoagglutinin) properties. This antibody was found to be monoclonal IgM lambda with specificity to the Pr2 antigen on red blood cells. CONCLUSIONS: Monoclonal IgM lambda anti-Pr is a rarely found cold agglutinin antibody. In this report we describe the clinical course of a patient who had this antibody, which not only agglutinated red cells in the cold but also had cryoglobulin properties. The clinical illness of this man was characterized by severe acrocyanosis and digital necrosis with eventual organ necrosis and death. We also review the literature on cold induced disease due to monoclonal anti-Pr IgM lambda antibody. Our patient was found to be unique among the reports reviewed. Our case is the first to report both cold agglutinin and cryoglobulinemic properties with the evaluation of the thermal amplitudes of these activities of the antibody. Also, unlike the lymphoproliferative malignancy observed in the cold agglutinin-associated disease in the other reports, our patient's disease was associated with a monoclonal B-cell expansion on the spectrum between benign monoclonal gammopathy and a low grade lymphoproliferative disorder.

The Collaborative Hospital Transfusion Study: variations in use of autologous blood account for hospital differences in red cell use during primary hip and knee surgery.

BACKGROUND: Red cell use in patients undergoing Diagnosis Related Group (DRG) 209 procedures (major joint and limb reconstruction procedures of the lower extremities) has been shown to have large, unexplained interhospital variations. STUDY DESIGN AND METHODS: Abstracted records of 2590 consecutive DRG 209 patients at five university hospitals from January 1992 to December 1993 were stratified by procedure and preoperative blood deposit status. Patient characteristics and transfusion and in-hospital outcomes were compared across hospitals. RESULTS: Blood use among patients who did not preoperatively deposit blood was similar across hospitals. Significant differences were found across hospitals for total hip replacement patients in the percentage of patients preoperatively depositing blood (59-80%), percentage of patients receiving transfusion(s) (51 to > 99%), the mean number of units collected per patient (1.6-2.9), and the mean number of unused autologous units per 100 patients (1-185). No significant differences were found in the percentage of those who deposited blood and then required allogeneic units. There was little variability in length of hospital stay or in last hematocrits. Findings were similar for total knee replacement patients. CONCLUSIONS: Interhospital variations in red cell use for primary total hip and knee reconstruction are primarily due to hospital-specific differences in autologous blood collection and transfusion.

The specific hospital significantly affects red cell and component transfusion practice in coronary artery bypass graft surgery: a study of five hospitals.

BACKGROUND: Interhospital differences in blood transfusion practice during coronary artery bypass graft (CABG) surgery have been noted, but the underlying issues have not been identified. STUDY DESIGN AND METHODS: Records of 3217 consecutive CABG cases in five university teaching hospitals in 1992 and 1993 were stratified by hospital, type of revascularization conduit, patients' sex, and other factors. Statistical methods were used to compare patient characteristics, transfusion outcomes, and hospital outcomes. RESULTS: Forward two-step logistic regression using patient likelihood of red cell transfusion factors in the first step and the specific hospital in the second step revealed a significant effect of hospital on the delta odds ratios for red cell transfusion. This finding was confirmed by analyses of a highly stratified subset of cases, males in diagnosis-related group 107 (primary cases of coronary bypass without coronary catheterization) who underwent revascularization with venous and internal mammary artery grafts, revealing variations among hospitals from 109 to 457 units of red cells transfused per hundred cases. Corresponding variations in transfusions of all blood components were from 324 to 1019 units by hospital. Variation in red cell transfusion practice among surgeons in the same hospital was not responsible for these interhospital differences. CONCLUSION: The effect of the specific hospital on transfusion practice is attributed to institutional differences that, through reasons of training or hierarchy, become ingrained in hospitals.

Determinants of red cell, platelet, plasma, and cryoprecipitate transfusions during coronary artery bypass graft surgery: the Collaborative Hospital Transfusion Study.

BACKGROUND: Very little is known about the determinants of blood transfusions in patients undergoing coronary artery bypass graft surgery. STUDY DESIGN AND METHODS: To identify factors that influenced the transfusion of red cells, platelets, plasma, and cryoprecipitate, statistical methods were used to study 2476 consecutive diagnosis-related group 106 and 107 patients in five teaching hospitals who underwent coronary artery bypass surgery between January 1, 1992, and June 30, 1993. RESULTS: The likelihood of red cell transfusion was significantly associated with 10 preoperative factors: 1) admission hematocrit, 2) the patient's age, 3) the patient's gender, 4) previous coronary artery bypass surgery, 5) active tobacco use, 6) catheterization during the same admission, 7) coagulation defects, 8) insulin-dependent diabetes with renal or circulatory manifestations, 9) first treatment of new episode of transmural myocardial infarction, and 10) severe clinical complications. Platelet and/or plasma transfusions were strongly associated with the dose of red cells transfused. Transfusion requirements and other in-hospital outcomes were associated with patient characteristics, surgical procedure (reoperation vs. primary procedure), and the conduits used for revascularization (venous graft only, venous and internal mammary artery graft, or internal mammary artery graft only). Blood resource use and donor exposures were evaluated with respect to the risk to patients of contracting hepatitis C virus and human immunodeficiency virus infections. CONCLUSION: The classification of coronary artery bypass graft patients on the basis of attributes known preoperatively and by conduits used yields subsets of patients with distinctly different transfusion requirements and in-hospital outcomes.

Security and patient management in a forensic hospital.

Emphasizing the use of humane techniques and interventions, the security model discussed here has proven more effective, more therapeutic, and more economical than traditional approaches.

Efficacy of vital home bleaching.

The nightguard vital bleaching technique has become a very common and accepted procedure for many dental practitioners. Much has been written about the procedure's history, safety and technique; little has been done to quantify the specific color changes of teeth resulting it. This clinical study attempted to give a numerical value to the color change through the use of a light transmission densitometer. The maxillary teeth of twenty-five patients were treated as the control. A significant whitening was observed for a majority of the patients during the four-week duration of the study.

The effect of nonnutritive sucking on heart rate in preterm infants.

A laboratory and a field experiment used within-subject designs to test the hypothesis that nonnutritive sucking (NNS) reduces heart rate (HR) in preterm infants. Infants in Experiment A were provided a standard pacifier nipple for 30 min under strictly controlled conditions. In the field Experiment B, nursing staff provided infants with a standard pacifier during alternate intervals in a sequence of four interfeed intervals spanning 12 hr. NNS significantly reduced average HR in each experiment. Given the strongly positive relationship between HR and energy expenditure, these results suggest that NNS reduces energy expenditure in preterm infants. Such an effect, in turn, could help to explain how the opportunity to engage in NNS enhances growth in preterms.

Mechanism of NaCl transport-stimulated prostaglandin formation in MDCK cells.

Recently we have found that stimulation of NaCl transport in high-resistance MDCK cells enhances their prostaglandin formation. In the present study, we investigated the mechanisms by which prostaglandin formation could be linked to the ion transport in these cells. We found that stimulation of transport caused a transient stimulation of prostaglandin formation lasting 5-10 min. The rise in prostaglandin formation was paralleled by a rise of free intracellular arachidonic acid. Analysis of membrane lipids revealed that the rise of free arachidonic acid was paralleled by a loss of arachidonic acid from polyphosphoinositides. We failed to obtain indications for the stimulation of calcium-dependent phospholipase A2. However, we did obtain evidence that the incorporation of arachidonic acid into phospholipids was diminished during stimulation of ion transport, indicating a decreased rate of reesterification. Despite the fact that there was no significant fall in total cellular ATP on stimulation of ion transport, we found a high and transient rise of lactate production of the cells on stimulation of the ion transport indicating an alteration of the ADP/ATP ratio. Moreover, prostaglandin formation and lactate formation were linearly correlated in this situation. When glucose utilization was inhibited by mannoheptulose, the rise in lactate formation was abolished, whereas that of PG formation was unaltered, indicating that lactate formation and prostaglandin formation were not causally linked on stimulation of ion transport. Our results suggest that an increase in the rate of sodium chloride transport by MDCK cells stimulates formation by an inhibition of reesterification of free arachidonic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

A Minority Health Careers Exposure Program.

The University of Tennessee-Memphis (UT-M) Health Careers Exposure Program was initiated in response to the complaint of minority college students that basic medical science laboratories and clinical centers at private and state-supported health-science organizations in Tennessee were inaccessible to them as career-motivating, summer work experiences. The preceptor-apprentice relationship was the means utilized to expose and stimulate minority college students to enter health careers in this study. The formal activity was usually conducted for eight to ten weeks of summer vacation in the basic science and clinical facilities on the UT-M campus.A survey of the current career activities of former apprentices suggests that direct exposure of academically talented, minority college students to health careers is a factor that increases the number entering the health professions.

Evaluation of artificial plasma for maintaining the isolated canine brain.

The use of canine erythrocytes suspended in artificial plasma to maintain the isolated brain was investigated in 18 preparations. Two plasmas were studied: One (AP1) contained electrolytes, amino acids, and albumin; the other (AP2) was similar to CSF and contained a mixture of 37 organic nutrients plus electrolytes and albumin. The CMRO2, CMRglu, and cerebral vascular resistance (CVR) were measured during 2 h of perfusion, and tissue high-energy phosphates were measured at the end of perfusion. The AP1 and AP2 groups were compared with control preparations perfused with canine red blood cells suspended in buffy coat-poor canine plasma. Both CMRO2 and ATP decreased to 60% of the control value; CVR increased to 187% of the control value in both groups following 2 h of perfusion. After 2 h of perfusion, the calculated value of intracellular pH (pHi)--based on creatine kinase equilibrium--remained normal (6.96) for the control brains, but decreased to 6.49 and 6.63, respectively, for the AP1- and AP2-perfused brains. Thus, there appears to be an eventual disruption of normal oxidative metabolism resulting in energy failure, possibly caused by the absence of an essential nutrient from the artificial plasma. For studies of intermediary metabolism in isolated normothermic brain, diluted whole blood appears to be the perfusate of choice.

Bohr effect data for blood gas calculations.

The oxygen dissociation curve (ODC) and Bohr effect of human blood were measured over a wide range of acid-base conditions and blood-O2 saturations at normal and low 2,3-diphosphoglycerate (DPG) concentrations. The fixed-acid Bohr factor (H+ titration) was relatively constant as a function of O2 saturation. At normal DPG levels, the H+ Bohr factor was not dependent on PCO2 except for a modest increase (in absolute magnitude) at very low PCO2 (7 Torr). For low DPG blood, the H+ Bohr factor decreased markedly with increasing PCO2 such that at PCO2 101 Torr, delta log PO2/delta pH varied between 0 and -0.13. The CO2 Bohr factor (CO2 titration) was strongly dependent on O2 saturation, being greatest at low O2 saturation. For normal DPG blood, this factor did not differ significantly at base excess (BE) +0.1 and +19.5 mmol/l, but decreased slightly at BE -20.3 mmol/l. For low DPG blood this factor showed a modest decrease with BE from -0.5 to +19.5 mmol/l but increased appreciably at BE -18.6 mmol/l. The data indicate that the Bohr factor may vary from unmeasurable levels to -0.93 under physiological and pathophysiological conditions. Results allow calculation of the shape and position of the ODC under the diverse conditions which may attend gas exchange.