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Various prognostic factors are associated with the survival of patients with parotid mucoepidermoid carcinoma (MEC). The aim of this systematic review is to summarize the clinical and pathologic prognostic factors on survival outcomes in patients with parotid MEC.Articles published from database inception to July 2020 on OVID Medline, OVID Embase, Cochrane Central, and Scopus.Studies were included that reported clinical or pathologic prognostic factors on survival outcomes for adult patients with parotid MEC. Data extraction, risk of bias, and quality assessment were conducted by 2 independent reviewers.A total of 4290 titles were reviewed, 396 retrieved for full-text screening, and 18 included in the review. The average risk of bias was high, and quality assessment for the prognostic factors ranged from very low to moderate. Prognostic factors that were consistently associated with negative survival outcomes on multivariate analysis included histologic grade (hazard ratio [HR], 5.66), nodal status (HR, 2.86), distant metastasis (HR, 3.10-5.80), intraparotid metastasis (HR, 13.52), and age (HR, 1.02-6.86). Prognostic factors that inconsistently reported associations with survival outcomes were TNM stage, T classification, and N classification.Histologic grade, nodal status, distant metastasis, intraparotid metastasis, and age were associated with worse survival outcomes. These prognostic factors should be considered when determining the most appropriate treatment and follow-up plan for patients with parotid MEC.

High carbohydrate, low fat (HCLF) diets have been the predominant nutrition strategy for athletic performance, but recent evidence following multi-week habituation has challenged the superiority of HCLF over low carbohydrate, high fat (LCHF) diets, along with growing interest in the potential health and disease implications of dietary choice. Highly trained competitive middle-aged athletes underwent two 31-day isocaloric diets (HCLF or LCHF) in a randomized, counterbalanced, and crossover design while controlling calories and training load. Performance, body composition, substrate oxidation, cardiometabolic, and 31-day minute-by-minute glucose (CGM) biomarkers were assessed. We demonstrated: (i) equivalent high-intensity performance (@∼85%VO2max), fasting insulin, hsCRP, and HbA1c without significant body composition changes across groups; (ii) record high peak fat oxidation rates (LCHF:1.58 ± 0.33g/min @ 86.40 ± 6.24%VO2max; 30% subjects > 1.85 g/min); (iii) higher total, LDL, and HDL cholesterol on LCHF; (iv) reduced glucose mean/median and variability on LCHF. We also found that the 31-day mean glucose on HCLF predicted 31-day glucose reductions on LCHF, and the 31-day glucose reduction on LCHF predicted LCHF peak fat oxidation rates. Interestingly, 30% of athletes had 31-day mean, median and fasting glucose > 100 mg/dL on HCLF (range: 111.68-115.19 mg/dL; consistent with pre-diabetes), also had the largest glycemic and fat oxidation response to carbohydrate restriction. These results: (i) challenge whether higher carbohydrate intake is superior for athletic performance, even during shorter-duration, higher-intensity exercise; (ii) demonstrate that lower carbohydrate intake may be a therapeutic strategy to independently improve glycemic control, particularly in those at risk for diabetes; (iii) demonstrate a unique relationship between continuous glycemic parameters and systemic metabolism.

Infrared (IR) lasers have recently been tested as an alternative to electrosurgical and ultrasonic laparoscopic devices for optical sealing of blood vessels. IR laser technology previously demonstrated faster sealing times, reduced thermal spread, and lower device temperatures during experimental studies. However, current commercial laparoscopic devices incorporate electrical impedance and/or temperature sensors as real-time, closed-loop, feedback to indicate successful blood vessel seals. This preliminary study explores an infrared laser system for sealing and optical coherence tomography (OCT) as a potential feedback system for successful vessel seal verification. A 1470-nm diode laser delivered an incident power of 30 W for an irradiation time of 5 s using an 8 × 2 mm linear beam, for creating strong seals in porcine renal blood vessels under compression. After sealing the blood vessels, OCT was performed on unsealed and sealed vessel regions for comparison. Standard vessel burst pressure (BP) measurements confirmed successful seals after OCT. Integrated reflectance intensity in OCT A-scans decreased by an average of 20 ± 6% in sealed versus native vessels of 2.4 ± 0.4 mm diameter. Vessel BP measured 532 ± 239 mmHg, with all vessels (n = 25) recording a successful BP > 180 mmHg (hypertensive blood pressure). Unsealed vessels demonstrated significantly deeper imaging marked by a continuous decay in reflected intensity, while sealed vessels showed subsurface reflectance intensity peaks, immediately followed by a rapid decay in reflectance intensity. These markers are consistent with increased light scattering and decreased optical penetration depth upon thermal coagulation of tissues. A-line OCT data consistently differentiated between sealed and unsealed blood vessel regions. Future work will involve OCT integration into the laparoscopic device for real-time optical feedback during IR laser sealing.

Strawberry mild yellow edge virus (SMYEV) is a member of the genus Potexvirus, family Alphaflexiviridae. It is one of the most common pathogenic viruses infecting cultivated strawberries worldwide. In this study, we investigated the genetic diversity of SMYEV in strawberry fields that were severely affected by strawberry decline disease in the eastern Canadian provinces of New Brunswick, Nova Scotia, Prince Edward Island and Quebec. A total of 134 SMYEV coat protein (CP) gene sequences, representing 85 nucleic acid haplotypes, were identified in 56 field samples. A highly divergent SMYEV population was found in all four provinces, but there was little genetic differentiation among the populations, and moreover, the Canadian SMYEV isolates formed a unique dissimilar, genetically divergent population group when compared to those reported in other countries. Phylogenetic analysis revealed three new SMYEV subclades that consisted mainly of Canadian variants and were composed of 76 sequence haplotypes (76/85, 88%). Mixed infections by different SMYEV variants were observed in 38 samples (38/56, 68%). Evolutionary analysis suggested that the SMYEV strains in eastern Canada possibly originated outside of Canada but adapted to conditions in the region through genetic mutations.

Introduction/Background The therapeutic relationship may be critical to rehabilitation outcome. However, knowledge advance is hampered by existing measures, which were not designed for use in the rehabilitation context and fail to capture essential elements. Drawing on a conceptual framework developed through prior research, we aimed to develop a robust measure of therapeutic relationship, tailored to the rehabilitation context. Material and method A measure development study drawing on steps proposed by Prior et al., 2011. We undertook a literature search to identify existing measures of therapeutic relationship. All items were extracted and mapped against our conceptual framework. We removed duplicate and conceptually incongruent items, and developed new items for aspects not already captured. We reworded items to ensure consistency in item scoring direction and language. A preliminary pool of 68 items were then piloted with rehabilitation clients using cognitive interviewing methods to determine their comprehensibility, acceptability, relevance and answerability. The research team met to examine the data and identified items for deletion or revision. Results Clients (n = 13) were drawn from a diversity of contexts and included people with neurological (n = 5), long-term chronic (n = 4), and acute (n = 4) conditions. We deleted 32 and reworded eight items in response to feedback. Reasons for deletion included overlap with other items (n = 22), not relevant across populations/context (n = 5), ambiguous (n = 4), or too global (n = 1). Conclusion A 36-item scale was derived aiming to measure therapeutic relationship in rehabilitation. This measure is now being pilot tested with a larger cohort of clients to further refine the measure using Rasch analysis.

Development of procedures yielding substantial blood alcohol concentrations during voluntary access to an alcohol solution in mice is necessary to further characterize genetic and neurobiologic mechanisms underlying alcohol self-administration. Although, in experimental situations, some populations of mice readily drink an alcohol solution, results from previous studies have not typically revealed high blood alcohol concentrations after voluntary access, probably because of the high alcohol metabolism rate in mice. Toward development of a murine drinking model, 36 selectively bred high-alcohol-preferring mice of both sexes were subjected to a 30-min scheduled-access procedure by using saccharin fading to gradually introduce an alcohol solution. Mice had ad libitum access to food and water 24 h a day. The alcohol solution was available 1 h after the start of the dark part of the cycle for 30 min per day, 5 days per week. After complete removal of saccharin from the drinking tubes, mice consistently drank 1.4 g/kg of a 10% [volume/volume (vol./vol.)] alcohol solution in 30 min. Analysis of tail blood samples, taken immediately after the end of the 30-min access period, indicated blood alcohol concentrations were tightly correlated with alcohol intakes (range, 6-130 mg/dl; average, nearly 60 mg/dl). A concentration-response function of 10%, 12%, 15%, 18%, and 21% (vol./vol.) alcohol solutions indicated an inverted U-shaped relation between alcohol intake and alcohol concentration, with peak intake of greater than 1.75 g/kg per 30 min when a 15% alcohol solution was available. No sex differences were seen. These findings indicate the utility of this procedure in obtaining pharmacologically relevant blood alcohol concentrations after voluntary oral self-administration of an alcohol solution in mice.

An industrial vacuum arc remelting experiment was carried out at Cytemp Specialty Steel Corp. (Titusville, PA) during which a 0.432-m-diameter Alloy 718 electrode was remelted into a 0.508-m-diameter ingot. The purpose of the experiment was to investigate the response of the arc voltage distribution properties (mean, standard deviation, and skewness) and the drip-short frequency to melting current, electrode gap, and CO pressure. The responses were characterized by recording and analyzing changes in the temporally averaged properties. Each independent variable was systematically varied in accordance with a modified Yates order factor space experimental design within the following ranges: melting current, 5000 to 11,200 A; electrode gap, 0.004 to 0.056 m; and CO pressure, 0.40 to 14.7 Pa. Statistical models were developed describing the correlation between the averaged arc voltage distribution properties and the independent variables. The models demonstrate that all of the voltage distribution properties, as well as the drip-short frequency, are directly related to electrode gap. An arc column model is presented to account for the mean arc voltage properties and the model is used to estimate the arc column pressure. The potential usefulness of the distribution properties as process diagnostics and control responses is evaluated.

The objective of this study was to examine the validity of multifrequency direct segmental bioelectrical impedance analysis (DSM-BIA) measures to detect changes in the hydration status of wrestlers after they underwent 3% acute dehydration and a 2-hour rehydration period. Fifty-six National Collegiate Athletic Association wrestlers: (mean ± SEM); age 19.5 ± 0.2 years, height 1.73 ± 0.01 m, and body mass (BM) 82.5 ± 2.3 kg were tested in euhydrated, dehydrated (-3.5%), and 2-hour rehydration conditions using DSM-BIA to detect the changes in hydration status. The hydration status was quantified by measuring the changes in plasma osmolality (P(osm)), urine osmolality (Uosm), urine specific gravity (U(sg)), BM, and weighted segmental impedance at frequencies of 5, 20, 50, 100, and 500 kHz. Weighted segmental impedance significantly increased after a 3.5% reduction in the body weight for all the 5 frequencies evaluated, but it did not return to baseline at 2-hour rehydration. P(osm) (303 ± 0.6 mOsm·L(-1)), Uosm (617 ± 47 mOsm·L(-1)), and U(sg) (1.017 ± 0.001) all significantly increased at postdehydration and returned to baseline at 2-hour rehydration. Estimations of extracellular water were significantly different throughout the trial, but there were no significant changes in the estimations of the total body water or intracellular water. The results of this study demonstrate the potential use of DSM-BIA as a field measure to assess the hydration status of wrestlers for the purpose of minimal weight certification before the competitive season. When employing DSM-BIA to assess the hydration status, the results indicated that the changes in weighted segmental impedance at the frequencies evaluated (5, 20, 50, 100, and 500 kHz) are sensitive to acute changes in dehydration but lag behind changes in the standard physiological (plasma and urinary) markers of hydration status after a 2-hour rehydration period.

TRW is currently under contract to produce the US Army's new Command, Control, and Intelligence (C2I) system for its forward areas air defense elements. The system design is characterized by automatic dissemination of tactical aircraft data as well as battlefield intelligence information. The Human Factors Engineering effort on this program has been responsible for all aspects of the design of the operator interface. The effort has focused attention on the value of interactive prototypes for the purpose of detailed design. This paper describes the Human Factors design process on this program and presents a two-phase approach to a rapid prototyping effort. Future plans to use objective data collected from prototype work in conjunction with a formal task analysis are also discussed.

Two experiments are presented that examine automaticity and transfer of mental rotation skills. The data from these experiments were analyzed using a curve-fitting technique that represents a departure from traditional methods used to analyze transfer. The first experiment demonstrated significant positive transfer from one letter stimulus to another. The second experiment examined the transfer of rotation skills from a letter to an abstract shape. This experiment demonstrated a reduced amount of transfer from letters to an abstract shape. Both experiments indicated that mental rotation skills may become automatic with practice.

Reported is an experiment which was designed to (1) test the strength-precision relationship of grip and shoulder strength with competitive pistol shooting scores using a nationally ranked collegiate pistol team and (2) determine the effects of a very brief, specifically focused, intense grip and shoulder strength training program (10 min, 3 times per week for 8 weeks) on strength and shooting performance. All members of the Pennsylvania State University Navy ROTC Pistol Team (n = 12) were divided into two matched groups according to pre-test shooting scores. Both groups received identical shooting instruction and practice, but the training group participated in an eight-week strength development program while the control group did not. Maximum isometric strength (peak and 4-sec average force) measures were obtained from electronic output of a hand dynamometer and strain gauge (deltoid contraction from a lateral horizontal shooting position against an arm cuff). Shooting scores (slow fire, timed fire, rapid fire, and total) were used as performance measures. The 24 intense but brief exercise bouts did not produce group training effects, despite painstaking efforts to use (1) exercises documented to produce training effects, (2) subjects who were highly motivated, (3) accurate and reliable strength testing equipment, and (4) a program which exercised to fatigue each day the target muscles. This finding is particularly alarming because of the strong body of literature suggesting the effect should have occurred. It also suggest that the time spent in strength training might better be spent in shooting. Nonetheless, robust strength-performance correlations were obtained, particularly in two areas: (1) slow fire shooting scores with grip strength and (2) timed and rapid fire with deltoid strength. Furthermore, individual subject analysis revealed that those that improved in strength also improved in shooting skill. This training was effective for improving strength and scores in some subjects, especially in producing increases in deltoid strength concomitant with improvements in timed and rapid fire scores. This work has implications for all types of free-limb shooting activities, for military and civilian populations, and for novice and elite performers.

Catecholamines have multiple metabolic and fluid-electrolyte as well as cardiovascular effects, and their levels in plasma respond to alterations in nutrient and sodium intakes. Plasma norepinephrine, epinephrine, and dopamine were measured in 12 obese nondiabetic subjects before and after 400 kcal/day diets of either protein or glucose, followed by total fasting, and then by hypocaloric refeeding, each for 14-day periods. Measurements were made in the supine and upright posture and during and after 6-10 min of exhaustive exercise at 80% maximal VO2. Sodium intake varied with the nutrients ingested, being markedly decreased with the 400 kcal/day diets and fasting. Norepinephrine levels were higher in fasting than base line while subjects were lying or standing and after recovery from exercise. Those of epinephrine were elevated on standing. No differences were found after the 400 kcal/day diets, with protein and glucose yielding equivalent results. In contrast, refeeding was associated with lower norepinephrine levels than all other diets while subjects were lying or standing and after recovery from exercise. Peak levels of norepinephrine and epinephrine with exercise were indistinguishable among diets. Fasting was associated with lower systolic and diastolic blood pressures and lower responses to standing and exercise than base line, whereas upright heart rate was greater and that during exercise less than base line. Significant though less extensive changes occurred with the other diets. Thus both electrolyte status and nutrient intakes interact to determine net catecholamine responses, and the former seem to override the latter.(ABSTRACT TRUNCATED AT 250 WORDS)

There is increasing evidence that platelets play an important role in the pathogenesis of acute ischemic heart disease. Therefore an understanding of factors that influence platelet performance is important. This study was undertaken (1) to characterize during evolving myocardial infarction platelet activity in the peripheral circulation and across the ischemic/infarcting myocardial compartment, the locus of presumed platelet hyperactivity, and (2) to evaluate the effects of prostacyclin (PGI2), a most potent antiplatelet agent and vasodilator. A total of 59 patients with evolving myocardial infarction were studied. Twenty-two patients were instrumented with arterial and coronary sinus catheters and received intravenous infusion of PGI2, 13 +/- 4.5 ng/kg/min (mean +/- SD), for 90 min. In 15 patients with anterior myocardial infarction, transcardiac platelet function and response to PGI2 were studied. Plasma levels of beta-thromboglobulin (beta-TG) and of thromboxane B2 (TxB2), in vivo measures of platelet activity, were elevated three- and 10-fold. 6-Keto-prostaglandin F 1 alpha, the stable end product of PGI2, was less than 10 pg/ml, reflecting a leftward shift of the TxB2/PGI2 ratio. Platelets circulating during evolving myocardial infarction ("ischemic platelets") were hyperaggregable in response to ADP and relatively resistant to PGI2, both in vivo and in vitro. Concentrations of platelet cyclic AMP and the cyclic AMP response to PGI2 were diminished. The platelet hyperreactivity, expressed by plasma beta-TG, platelet aggregation, and PGI2-induced inhibition of aggregation, was most intense early during infarct evolution and decreased with time. The increased platelet performance resulted in "platelet fatigue," indicated by decreased contents of beta-TG of the ischemic platelet and decreased TxA2 production in response to collagen. However, the ischemic platelet produced twice normal TxA2 in response to arachidonic acid (stimulus and substrate), demonstrating a heightened metabolic capacity. TxA2 was produced across the ischemic/infarcting compartment in 10 of 15 patients with anterior myocardial infarction. The antiplatelet effect of PGI2 was greatly diminished. In summary, the data define an abnormal pattern of platelet behavior during evolving myocardial infarction, characterized by a proaggregatory environment, heightened platelet reactivity in both the peripheral and coronary circulation, and relative resistance to PGI2. The clinical consequences of the data are that the patient in the acute phase of myocardial infarction may benefit from suppression of platelet function and requires significantly greater doses of PGI2 than normal subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

To determine the causes of cardiac failure during cardiac tamponade in man, we studied left ventricular volume and function in eight patients during pericardiocentesis using gated equilibrium radionuclide ventriculography. In the seven patients with clinical and hemodynamic evidence of cardiac tamponade, end-diastolic and end-systolic volumes increased progressively as the initial 500 ml of fluid were removed; the most marked increase occurred during the removal of the first 200 ml of pericardial fluid. After removal of 500 ml of pericardial fluid, end-diastolic volume increased from 52 +/- 8 ml to 111 +/- 13 ml (p less than 0.05) and end-systolic volume from 17 +/- 5 ml to 34 +/- 7 ml (p less than 0.05). Additional aspiration of fluid resulted in no further changes in left ventricular volume. The ejection fraction averaged 70% before removal of fluid and was unchanged by pericardiocentesis. In the one patient who did not have hemodynamic evidence of tamponade, there were only minor changes in left ventricular volumes and ejection fraction. These data suggest that pump function of the left ventricle is well preserved in cardiac tamponade, and that the diminution in stroke volume and consequent cardiovascular collapse seen in tamponade are due to marked underfilling of the ventricle.

Pulmonary arterial early diastolic waves (V waves) were investigated in patients and experimental animals with mitral regurgitation. V waves exceeding systolic pressure in the pulmonary artery were recorded in the main pulmonary artery with micromanometer catheters both in patients and animals, eliminating the possibility of catheter artifact. In experimental animals, aortic closure preceded pulmonic closure by 33 +/- 12 msec at baseline. With the creation of acute mitral insufficiency, a pulmonary arterial V wave occurred in six of eight animals. Early pulmonic valve closure occurred only in the six animals with a pulmonary arterial V wave. In these animals, pulmonic closure preceded aortic closure by 28 +/- 7 msec during mitral insufficiency (p less than .05). Of 70 patients with severe mitral regurgitation at cardiac catheterization, 14 had a pulmonary arterial V wave. In five patients recordings with micromanometer catheters were made and early pulmonic closure was also observed in four of these patients who had pulmonary arterial V waves at rest or upon provocation. Patients with pulmonary arterial V waves had a more acute onset of symptoms, shorter duration of mitral regurgitation, higher pulmonary capillary wedge V waves, and lower pulmonary arterial resistances than patients without them and were more likely to have nonrheumatic mitral regurgitation.

To evaluate possible occult myocardial disease in 18 patients whose only major manifestation of heart disease was spontaneous ventricular tachycardia or fibrillation, right ventricular endomyocardial biopsies were performed. None of the patients had symptoms of ischemic or congestive heart disease, and at catheterization none had significant lesions of the coronary arteries or regional wall motion abnormalities of the left ventricle. The mean left ventricular ejection fraction (65 +/- 7%), mean right ventricular ejection fraction (55 +/- 9%), mean cardiac index (3.0 +/- 0.5 1/min/m2), mean right atrial pressure, mean pulmonary capillary wedge pressure, and mean pulmonary artery systolic pressure were normal. However, right ventricular endomyocardial biopsy specimens were abnormal in 16 of 18 (89%) patients: nine (50%) had changes of a significant, although nonspecific, cardiomyopathy with myocellular hypertrophy, interstitial and perivascular fibrosis, and vascular sclerosis; three (17%) had subacute inflammatory myocarditis; two (11%) had diffuse abnormalities of the intramyocardial arteries; and two (11%) had pathologic changes consistent with arrhythmogenic right ventricular dysplasia. In the two (11%) patients with normal biopsy specimens, one had Wolff-Parkinson-White syndrome and the other had mitral valve prolapse. Although histologic abnormalities were found in 89% of these patients, performance of right ventricular endomyocardial biopsies in this group of patients should be considered a research procedure. We conclude that the majority of patients who have serious ventricular arrhythmias but no apparent structural cardiac abnormalities have abnormal right ventricular biopsy specimens and that the arrhythmias may be the first manifestation of a variety of primary myocardial abnormalities.

BB rats of diabetes-prone lines develop a spontaneous Type 1 diabetic syndrome, with many immunological concomitants. No data are available as to the integrity of their islet beta cells prior to onset of the insulitis which proceeds to their selective destruction. We tested the effects of the beta-cytotoxins streptozotocin and alloxan on such rats, compared to Wistar and to non diabetes-prone BB control rats studied prior to usual age of diabetes onset. A dose-response of a single injection of the agents with respect to pancreatic insulin content 48 hr post-injection as well as to circulating insulin and glucose, weight, and lymphocyte counts was established. Clear dose-responses were found for pancreatic insulin content. Though less sensitive, plasma insulin and glucose values showed responses. Whereas some litters of diabetes-prone rats showed greater reductions of pancreatic insulin than controls after some doses of streptozotocin, overall results in 8-26 recipients of each dose showed no significant differences when compared with either BB or Wistar controls. With smaller numbers of diabetes-prone rats, the same was obtained for alloxan, though with fewer doses tested. The latter required the construction of an alloxan dose-response in normal Wistar rats. Thus, this study has not demonstrated a nonspecific increase in "fragility" of BB rat beta cells in response to these classical diabetogenic agents. This would be consistent with other data suggesting that the primary abnormality in the syndrome does not necessarily reside within the beta cell.

There is increasing evidence that platelets play an important role in the pathogenesis of acute ischemic heart disease. Therefore, an understanding of factors which impact on platelet performance is important. The present study was undertaken 1. to characterize during evolving myocardial infarction (MI) platelet activity in the peripheral circulation and across the ischemic/infarcting myocardial compartment, the locus of presumed platelet hyperactivity, and 2. to evaluate the effects of prostacyclin (PGI2), a most potent antiplatelet agent and vasodilator. A total of 59 patients with evolving MI were studied. 22 patients were instrumented with arterial and coronary sinus catheters and received intravenous infusion of PGI2, 13 +/- 4.5 ng/kg/min (mean +/- SD), for 90 minutes. In 15 of these patients, who had an anterior MI, transcardiac platelet function and response to PGI2 were studied. The results are as follows: Plasma levels of beta-thromboglobulin (beta-TG) and of thromboxane B2 (TxB2), in vivo measures of platelet activity, are elevated three and ten fold. 6-keto-prostaglandin F1 alpha, the stable end product of PGI2, is less than 10 pg/ml, reflecting a leftward shift of the TxB2/PGI2 ratio. Platelets, circulating during evolving MI ("ischemic platelets") are hyperaggregable in response to adenosine diphosphate and relatively resistent to PGI2, both in vivo and in vitro. Concentrations of platelet cyclic adenosine monophosphate and the cAMP response to PGI2 are diminished. The platelet hyper-reactivity is most intense early during infarct evolution and decreases with time. Transcardiac measurements indicate that thromboxane is produced across the ischemic/infarcting compartment in ten of 15 patients with anterior MI. The antiplatelet effect of PGI2 is greatly diminished. In summary, the data define an abnormal pattern of platelet behavior during evolving MI characterized by a pro-aggregatory environment, heightened platelet re-activity, both in the peripheral and coronary circulation, and relative resistance to PGI2. The clinical consequence of the data are that the infarct patient in the acute phase may benefit from platelet function suppression and requires significantly greater doses of prostacyclin than normal subjects. The data also suggest future directions for therapeutic manipulation of platelet hyper-reactivity in the setting of acute myocardial ischemia.

Immunological variables were studied in rats chronically exposed to high environmental temperature (35 degrees C). Responses were compared with those of rats at 25 degrees C both fed ad libitum and pair fed to the decreased intake found in heat-exposed rats. Heat-exposed rats showed slower delayed-type hypersensitivity responses to keyhole limpet hemocyanin. They showed lower counts of peripheral blood total T cells (OX19+) as well as helper T cells (W3/25+) and smaller numbers of splenic T cells. The thymus was decreased in size. Increased levels of serum IgG antitetanus toxoid antibodies were found in heat-exposed rats. [3H]-thymidine incorporation into Concanavalin A (ConA)-stimulated splenic lymphocytes was decreased in pair-fed rats but not significantly altered in heat-exposed rats compared with controls. Heat exposure alters some aspects of both cellular and humoral immune function in a manner different from that induced by comparable food restriction without heat exposure.

The spontaneously diabetic BB Wistar rat shows many characteristics analogous to human insulin-dependent diabetes (IDDM). These include inappropriately normal immunoreactive glucagon in the presence of hyperglycemia, absolute hyperglucagonemia with severe ketosis, and hyperresponsiveness to exogenous arginine in vivo. We used an in situ pancreas preparation to further study portal vein glucagon responses to intravenous arginine. In normal rats, magnitude of response was correlated with prestimulation levels. Basal levels were significantly increased in hyperglycemic diabetics compared to controls, but responses to arginine were attenuated in both absolute and relative terms. Comparisons of responses with poor and good prior diabetes control showed no significant differences. Thus, a further anomaly of glucagon secretion has been identified in these rats.

The metabolic and immunological effects of cyclosporine A given at onset of spontaneous Type I diabetes in BB rats were examined, as an analogy to the current use of this agent in newly-diagnosed human diabetics. Diabetes-prone (BBdp) rats were monitored until appearance of hyperglycemia, at which time treatment with both cyclosporine (10 mg/kg/day) and insulin was immediately started. Cyclosporine induced no remission in any rats and did not affect their daily insulin requirements. After 9 weeks of cyclosporine treatment, islet morphology showed the typical "end-stage" picture in all rats, with essentially total beta cell loss. Pancreatic insulin contents were less than 1% of normal levels. During the 9 weeks of cyclosporine treatment, there was a decrease in numbers of peripheral blood Ia-positive lymphocytes, an increase in OX8+ lymphocytes (suppressor/cytotoxic and natural killer cells) but no change in the other subsets. There was a significant increase in plasma creatinine. We conclude that this dose of cyclosporine started at onset of diabetes in BB rats is unable to arrest and/or reverse the beta cell destructive process.