Recurrent venous thrombosis as the presenting manifestation of acute lymphocytic leukemia: Leukemic cell procoagulant activity is not responsible for the hypercoagulable state

The association of cancer with clinical abnormalities of blood coagulation, including superficial thrombophlebitis, deep vein thrombosis (DVT), and disseminated intravascular coagulation (DIC) is well-known, particularly in patients with solid tumors and acute promyelocytic leukemia (APL). Less commonly appreciated is the potential for the development of venous thromboembolic disease (TED) in patients with acute lymphocytic leukemia (ALL). Multiple mechanisms have been implicated for the activation of coagulation in these patients, with an emphasis on the contribution made by the procoagulant properties of the tumor cells themselves. We present two cases of patients with pre-B cell ALL, both of whom developed recurrent TED as the presenting manifestation of their leukemia and/or heralding relapse. The blast cells from one of the patients were studied for the presence of procoagulant activity (PCA) and by Northern blot analysis for tissue factor (TF) messenger RNA (mRNA). Neither PCA nor TF mRNA could be identified in highly purified populations of the lymphoblast cells. We conclude that recurrent TED can be a manifestation of ALL and that mechanisms other than the release of tumor cell procoagulants should be sought to explain the pathogenesis of thrombosis in some patients. © 1995 Wiley-Liss, Inc.     

Heritage characteristics reported by a group of African-Americans who exhibit the pigment dispersion syndrome: a case-control study

Purpose: To investigate the racial heritage of a group of African-Americans who exhibit the pigment dispersion syndrome (PDS). Subjects and Methods: Ten unrelated African-American PDS patients (age range 13–59) from a primary eye care population in Chicago, Illinois, USA, were interviewed to determine their racial heritage. Since Caucasian and Native American heritage were commonly reported, 101 unaffected African-American control subjects (age range 18–55) were also interviewed to determine the reported frequency of these specific racial heritage characteristics. Results: Some degree of Caucasian heritage was reported by 100% of the PDS subjects and by 46.5% of controls. Native American heritage was reported by 90% of the PDS subjects and by 71.3% of controls. Based on these data, the PDS subjects were significantly more likely to report Caucasian heritage (Fisher's exact test, P=0.001) but they were not significantly more likely to report Native American heritage (P=0.282). In addition, the PDS subjects were significantly more likely to report Caucasian heritage from both parents (P=0.024) and more likely to report a combination of both Caucasian and Native American heritage (P=0.0006) than corresponding controls. In general, the PDS subjects had `light' or `medium' complexions. Conclusion: Results from this analysis are consistent with the hypothesis that non-African heritage, particularly Caucasian, is likely to be prevalent in the background of African-Americans who exhibit PDS. It is suggested that non-African heritage may not only be important for the transference of PDS causing genes, but it may also influence factors such as degree of iris pigmentation and rigidity which could influence iris contour and the subsequent expression of PDS in those who are genetically predisposed. Further investigation is needed to study the factors that influence the expression and severity of PDS among African-Americans, a population which traditionally has been considered to be rarely affected by this condition.     

Systolic blood pressure, not BIS, is associated with movement during laryngoscopy and intubation

OBJECTIVE: To compare bispectral index (BIS) values to hemodynamic variations, in order to evaluate adequacy of anesthesia during orotracheal intubation with muscle relaxants. METHODS: Forty-one patients ASA I-II, scheduled for elective peripheral surgery under general anesthesia with tracheal intubation were enrolled in the study. Fentanyl/thiopental followed by vecuronium were used for induction. Onset of relaxation was monitored at the orbicularis occuli (OO) muscle using train-of-four stimulation. Intubation was performed when no response at the OO was detected visually. Intubating conditions were noted. The "isolated forearm" technique was used to detect movement during laryngoscopy/intubation. BIS values, pulse rate (PR), and systolic pressure were recorded before induction, during laryngoscopy/intubation and 60 sec after intubation. RESULTS: Although intubating conditions were clinically adequate for all patients, ten out of 41 had movement of the isolated arm during laryngoscopy/intubation. BIS values were not significantly different for these patients: 67 (55-83) compared to those who had no movement: 60 (35-80), P = 0.6. During laryngoscopy, PR increased for all patients while systolic pressure increased significantly only in patients who moved: 125 (100-136) mmHg vs those who did not: 108 (67-140), P < 0.05. CONCLUSION: Systolic pressure elevations were associated with inadequate anesthesia as evaluated by the "isolated forearm" technique, during laryngoscopy/intubation. BIS values were not different between groups, suggesting that systolic blood pressure may be a better predictor of inadequate anesthesia under the circumstances described.     

Interstitial expression of alpha-SMA: an early marker of chronic renal allograft dysfunction.

BACKGROUND: Renal myofibroblast infiltration has been shown to be strongly associated with renal function decline in several chronic renal diseases. The purpose of the present study was to investigate whether early detection of myofibroblast infiltration using alpha-smooth-muscle actin (alpha-SMA) expression in time-zero biopsies predicts renal allograft dysfunction. METHODS: We studied renal tissue from 38 renal transplant patients from whom biopsies had been taken after vascular anastomosis during transplantation to ascertain whether myofibroblasts infiltration predicts renal graft survival. Immunohistochemistry was performed on time-zero biopsies to determine alpha-SMA expression, and this was compared to annual glomerular filtration rate (GFR) variation and other parameters including cold ischaemic time (CIT), donor and recipient age, number of acute rejections, and delayed graft function (DGF). GFR was measured by inulin clearance during of 3 years of follow-up after the transplantation. Progressors were defined as patients with an annual GFR decline >5 ml/min/year. RESULTS: We found a significant correlation between interstitial alpha-SMA expression in time-zero biopsies and GFR evolution during the post-transplantation course (r=0.60, P<0.001). Although progressors had greater interstitial alpha-SMA expression than non progressors (7.9+/-0.7 vs 4.3+/-0.4%), they showed only a tendency towards higher glomerular alpha-SMA expression. In addition, progressors had more interstitial fibrosis in time-zero biopsies than non-progressors. There was no relationship between alpha-SMA expression and CIT, donor and recipient ages, number of acute rejections, and occurrence of DGF. CONCLUSION: This study suggests that alpha-SMA evaluation in time-zero biopsies, especially the combination of alpha-SMA expression and interstitial fibrosis, can strongly predict chronic renal allograft dysfunctions.     

Gastric Bypass in Patients with BMI <40 but >32 Without Life-threatening Co-morbidities: Preliminary Report

Background: Surgical intervention is currently indicated for patients with BMI >40 or >35 with life-threatening comorbidities. Patients with BMI 32-40 without these comorbidities not only have the increased propensity to develop them but also suffer from similar psychosocioeconomic consequences. These patients may not respond to non-surgical treatment of obesity any better than those with BMI>40. The question has been raised whether to offer them surgical intervention. Methods: A study was carried out to determine outcome of surgery on patients with BMI >32 but <40 without life-threatening comorbidities but with either psychological, economic or social impairments affecting their quality of life. The approval of our Hospital Internal Review Board was obtained. In addition to routine evaluation for surgical intervention, these patients were required to have the approval of their primary care physician, be seen pre-operatively by a psychiatrist, and have a member of the family or a very close friend present at the time of discussion of operative risks and follow-up requirements. Patients committed to at least a 5-year follow-up. They were to be self-paying patients. The transected silastic ring vertical gastric bypass with a temporary gastrostomy was used. Results: 50 patients, 49 women and one man, were entered into the study between May 1, 1999 and April 30, 2000. 50% were self-pay, and the other 50% were able to obtain coverage through their insurance companies. There were few peri-operative complica tions and no deaths. The late complications include incisional hernias, dumping and transient alopecia. Hospital stay averaged 3.7 days. Follow-up has been 18-27 months. Weight loss has been excellent. Conclusion: Preliminary results of surgical intervention extended to patients with BMI 32-40 without life-threatening comorbidities but with psychosocioeconomic ramifications are very promising. Long term follow-up and comparison with other bariatric patients are planned.     

Neuroprotective activity of a nanoparticulate formulation of the glycineB site antagonist MRZ 2/576 in transient focal ischaemia in rats

The objective of the present study was to characterise the neuroprotective activity of the novel glycineB site NMDA (N-methyl-D-aspartate) receptor antagonist MRZ 2/576 (8-chloro-4-hydroxy-l-oxo- 1,2-dihydropyridazino[4,5-b]quinolin-5-oxide choline salt, CAS 202807-80-5) in a rodent model of focal cerebral ischaemia. Since the solubility of MRZ 2/576 at a physiological pH, is minimal and adequate concentrations can be achieved only at relatively high basic pH the in vivo use of the substance is substantially limited. Therefore, a special nanoparticle formulation was developed to provide means for lengthy i.v. administration of experimentally relevant doses within the physiological range of pH. Focal ischaemia of 75 min duration was induced in rats by a reversible occlusion of the middle cerebral artery (MCAo). MRZ 2/576 (18 mg/kg over 10 min followed by 18 mg/kg/h over 6 h) or placebo treatment was initiated immediately after onset of MCAo. Neurological deficit was evaluated daily for 3 consecutive days and then brain infarct analysis was performed. MRZ 2/576 significantly improved the neurological score at 24 h and 72 h post stroke (p < 0.05 vs. placebo). It also produced a 53.0% reduction of total infarct size, 60.4% of cortical and 42.3% of striatal infarction (p < 0.05 vs. placebo). Temporary drug-induced hypothermia and ataxia were observed during infusions. This leads to the conclusion that prolonged administration of the glycineB site antagonist MRZ 2/576 in form of the nanoparticle suspension ameliorates ischaemic damage induced by the transient MCAo in rats. The results suggest that nanoparticles hold promise as an effective strategy e.g. for substances with physico-chemical characteristics that otherwise would preclude them from pre-clinical development and/or clinical application.     

Personal goals as predictors of college student drinking motives,alcohol use and related problems

OBJECTIVE: Although there has been extensive research examining drinking motives, relatively little of that research has focused on those factors that might underlie drinking motives. The present study examines whether nonalcohol-related motives (personal goals) can predict drinking motives, self-reported drinking and alcohol-related problems in a college student sample. METHOD: For an experiment on "attitudes and drinking," 290 volunteer undergraduate students (169 women and 121 men) completed measures of daily goal functioning (Personal Projects Analysis), drinking motives (Drinking Motives Questionnaire), frequency and quantity of alcohol consumed and alcohol-related problems (Drinkers Inventory of Consequences). RESULTS: Using path analysis, it was found that nonalcohol-related goals serve as significant distal predictors of alcohol-related problems, with their effects almost entirely mediated by drinking motives and/or drinking level. Perceptions of life goals involving goal self-efficacy, meaningfulness and social support appear to be significant protective factors, and goal-related distress is a significant risk factor. CONCLUSIONS: The present study extends previous research by focusing on a more idiographic, personally meaningful manifestation of motivation through the evaluation of nonalcohol-related personal goals. The daily pursuits of college students were shown to be predictive of drinking and drinking-related problems, especially as mediated through drinking motives. The findings suggest that several goal mechanisms could be considered for their potential role in improving interventions.     

Evidence that intermittent,excessive sugar intake causes endogenous opioid dependence

OBJECTIVE: The goal was to determine whether withdrawal from sugar can cause signs of opioid dependence. Because palatable food stimulates neural systems that are implicated in drug addiction, it was hypothesized that intermittent, excessive sugar intake might create dependency, as indicated by withdrawal signs. RESEARCH METHODS AND PROCEDURES: Male rats were food-deprived for 12 hours daily, including 4 hours in the early dark, and then offered highly palatable 25% glucose in addition to chow for the next 12 hours. Withdrawal was induced by naloxone or food deprivation. Withdrawal signs were measured by observation, ultrasonic recordings, elevated plus maze tests, and in vivo microdialysis. RESULTS: Naloxone (20 mg/kg intraperitoneally) caused somatic signs, such as teeth chattering, forepaw tremor, and head shakes. Food deprivation for 24 hours caused spontaneous withdrawal signs, such as teeth chattering. Naloxone (3 mg/kg subcutaneously) caused reduced time on the exposed arm of an elevated plus maze, where again significant teeth chattering was recorded. The plus maze anxiety effect was replicated with four control groups for comparison. Accumbens microdialysis revealed that naloxone (10 and 20 mg/kg intraperitoneally) decreased extracellular dopamine (DA), while dose-dependently increasing acetylcholine (ACh). The naloxone-induced DA/ACh imbalance was replicated with 10% sucrose and 3 mg/kg naloxone subcutaneously. DISCUSSION: Repeated, excessive intake of sugar created a state in which an opioid antagonist caused behavioral and neurochemical signs of opioid withdrawal. The indices of anxiety and DA/ACh imbalance were qualitatively similar to withdrawal from morphine or nicotine, suggesting that the rats had become sugar-dependent.