In vitro expansion of hematopoietic cells for clinical application.
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Biomedical subjects
Publications and source records attributed to S M Silver.
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Analyses of scaled self-report data from Vietnam War veterans receiving inpatient treatment for Post-Traumatic Stress Disorder drawn during a program evaluation study suggested inpatient treatment as provided by the program resulted in significant improvement in the areas of Anxiety, Anger, Depression, Isolation, Intrusive Thoughts (of combat experiences), Flashbacks, Nightmares (of combat experiences), and Relationship Problems. Comparing the relative effects of the incremental addition of Eye Movement Desensitization and Reprocessing (EMDR), Relaxation Training, and Biofeedback found that EMDR was for most problems the most effective extra treatment, greatly increasing the positive impact of the treatment program.
Post-prostatectomy syndrome (PPS) is characterized by hyponatremia after absorption of glycine irrigant. To study the pathogenesis of this syndrome, adult male rats with ligated ureters were infused over 15 minutes with 7.5 ml/100 g body weight of isosmotic glycine (N = 9) or mannitol (N = 9) and were compared to non-infused, ureter-ligated controls (N = 9). Immediately post-infusion, plasma sodium had decreased similarly in glycine- and mannitol-infused animals (111 +/- 2 vs. 106 +/- 1 mmol/liter), but plasma osmolality remained at control levels in both groups (285 +/- 1 vs. 288 +/- 1 mOsm/kg). Two hours post-infusion, hyponatremia was stable in the mannitol group (108 +/- 1 mmol/liter), but in the glycine group plasma sodium increased significantly (to 120 +/- 1 mmol/liter). Plasma osmolality two hours post-infusion was maintained in both the glycine (287 +/- 2) and mannitol (292 +/- 2) groups. Brain water in glycine-infused animals (3.90 +/- 0.01 liter/kg dry wt) was not significantly different from the mannitol-infused group (3.85 +/- 0.01) and only 1.8% higher than non-infused controls (3.83 +/- 0.02). Brain tissue glycine did not differ between the three groups. In contrast, muscle water two hours post-infusion in the glycine group was 6% higher than mannitol-infused and 13% higher than non-infused animals. Muscle glycine content in the glycine group (67 +/- 4 mM/kg dry tissue) was increased when compared to both mannitol-infused (25 +/- 1) and non-infused (20 +/- 1) groups.(ABSTRACT TRUNCATED AT 250 WORDS)
We describe a case of peritonitis caused by Aureobasidium pullulans in a patient on continuous ambulatory peritoneal dialysis (CAPD). This dematiaceous fungus rarely causes infection in humans and to date has not been reported as an etiology of CAPD-associated peritonitis. The patient was managed successfully with peritoneal catheter removal and a prolonged course of intravenous amphotericin B, allowing resumption of CAPD. In vitro susceptibility testing confirmed sensitivity of this organism to amphotericin B.
Dialysis disequilibrium syndrome (DDS) is characterized by the neurologic deterioration and cerebral edema that occurs after hemodialysis. To investigate the pathogenesis of DDS, the effects of rapid hemodialysis on brain electrolytes, urea, and several organic osmolytes were studied in the rat. Forty-two h after bilateral ureteral ligation, 11 uremic rats were hemodialyzed for 90 min, yielding a decrease in plasma urea from 96 +/- 4 to 44 +/- 5 mM (p < 0.01). This group was compared with 10 uremic and 11 nonuremic animals that were not dialyzed. In dialyzed animals, compared with nondialyzed uremic controls, there was an increase in brain water (3.98 +/- 0.02 versus 3.77 +/- 0.02 L/kg dry wt; P < 0.01) and the brain to plasma (urea) ratio (1.32 versus 0.65). There was no significant difference in the brain content of sodium and potassium between groups. The retention of brain urea, despite the large decrease in plasma urea concentration, was able to account for the increase in brain water observed in rapidly dialyzed animals. Major organic osmolytes in the brain, including glutamine, glutamate, taurine and myoinositol, did not increase significantly after rapid dialysis. Cerebral edema in this model of DDS was primarily due to a large brain-to-plasma urea gradient, not to the formation of organic osmolytes.
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The subjective sleep disturbance in posttraumatic stress disorder (PTSD), including the repetitive, stereotypical anxiety dream, suggests dysfunctional rapid eye movement (REM) sleep mechanisms. The polysomnograms of a group of physically healthy combat veterans with current PTSD were compared with those of an age-appropriate normal control group. Tonic and phasic REM sleep measures in the PTSD subjects were elevated on the second night of recorded sleep. Increased phasic REM sleep activity persisted in the PTSD group on the subsequent night. During the study, an anxiety dream occurred in a PTSD subject in REM sleep. The results are consistent with the view that a dysregulation of the REM sleep control system, particularly phasic event generation, may be involved in the pathogenesis of PTSD. The finding of a specific disturbance of sleep unique to PTSD may have significant implications for the design of effective treatments for PTSD.
Veterans diagnosed with PTSD (PTSD in-treatment, N = 39), newly admitted to a comprehensive 90-day inpatient treatment program, were tracked at 4-week intervals from admission to discharge. Two control groups were also tracked over 12-week periods--one of previously PTSD diagnosed and treated veterans (PTSD out-of-treatment, N = 26), and a second that combined non-PTSD Vietnam era veterans (N = 17) and non-veterans (N = 16) (non-PTSD nontreatment). As measured by the Penn Inventory for PTSD, 48% of those who completed treatment showed some or substantial gains, 39% showed no gain, and 13% reported some increase in symptoms at the time of discharge. Several patterns were observed on other assessment measures. One year follow-up for those who completed treatment showed a return to pretreatment levels on the PTSD symptom measures employed in this study. These results are discussed in relation to other treatment program outcome studies as a baseline for further research.
A subjective disturbance of sleep, including the occurrence of repetitive, stereotypical anxiety dreams, is characteristic of posttraumatic stress disorder (PTSD). The phenomenology of the PTSD anxiety dream has seemed most consistent with an underlying rapid eye movement (REM) sleep dysfunction. However, motor behavior reportedly can accompany PTSD dreams, and normal REM sleep typically involves a nearly total paralysis of the body musculature. As a means of understanding this discrepancy, anterior tibialis muscle activity during sleep was studied in a group of Vietnam combat veterans with current PTSD and in an age-matched normal control group. The PTSD subjects had a higher percentage of REM sleep epochs with at least one prolonged twitch burst; they also were more likely to have periodic limb movements in sleep, during nonrapid eye movement sleep. Both these forms of muscle activation also have been observed in REM behavior disorder (RBD), a parasomnia characterized by the actual enactment of dream sequences during REM sleep. The identification of RBD-like signs in PTSD adds to the evidence for a fundamental disturbance of REM sleep phasic mechanisms in PTSD.
Severe, symptomatic hyponatremia is often treated urgently to increase the serum sodium to 120 to 130 mmol/L. Recently, this approach has been challenged by evidence linking "rapid correction" (> 12 mmol/L per day) to demyelinating brain lesions. However, the relative risks of persistent, severe hyponatremia and iatrogenic injury have not been well quantified. Data were sought on patients with serum sodium levels < or = 105 mmol/L from the membership of the American Society of Nephrology. Respondents were given a report form asking specific questions regarding the cause of hyponatremia, presenting symptoms, rate of correction, and neurologic sequelae. Data on 56 patients were analyzed. Fourteen developed posttherapeutic complications (10 permanent, 4 transient) after correction to a serum sodium > 120 mmol/L. Eleven of these 14 patients (including 3 with documented central pontine myelinolysis) had a biphasic course in which neurologic findings initially improved and then worsened on the second to sixth day. Posttherapeutic complications were not explained by age, sex, alcoholism, presenting symptoms, or hypoxic episodes. Increased chronicity of hyponatremia and a high rate of correction in the first 48 h of treatment were significantly associated with complications. No neurologic complications were observed among patients corrected by < 12 mmol/L per 24 h or by < 18 mmol/L per 48 h or in whom the average rate of correction to a serum sodium of 120 mmol/L was < or = 0.55 mmol/L per hour. It was concluded that patients with severe chronic hyponatremia are most likely to avoid neurologic complications when their electrolyte disturbance is corrected slowly.
Although rare cells expressing the bcr/abl fusion transcript can be detected by the polymerase chain reaction (PCR) in patient blood or marrow after allogeneic bone marrow transplant (BMT) for Philadelphia chromosome (Ph+)-positive chronic myelogenous leukemia (CML), the prognostic significance of this finding is unknown. This paper reports clinical, cytogenetic, and molecular data derived from 64 CML patients following allogeneic BMT. Nested primer PCR was performed on patient blood and bone marrow samples to detect the presence of residual bcr/abl (+) cells in CML patients considered to be in clinical remission at the time of study. Bcr/abl transcripts were detected in 37 of 64 patients for at least one timepoint post-BMT. Thirteen of these 37 bcr/abl (+) patients have subsequently relapsed, as defined by clinical and/or persistent cytogenetic findings, in contrast to 0 relapses among the 27 bcr/abl (-) patients (P = .0025). The median time from first (+) bcr/abl PCR signal to relapse was 150 days (range 90 to 832). Fifty-four patients were studied at two or more timepoints post-BMT: five of eight patients persistently bcr/abl (+) have relapsed; 5 of 23 patients with both bcr/abl (+) and (-) assays during follow-up have relapsed; and none of 23 patients persistently (-) have relapsed (cumulative actuarial relapse rates 77%, 20%, and 0%, respectively, P = .0017). These data indicate that among CML patients in apparent clinical remission after BMT, nested primer bcr/abl PCR can define subgroups with low, intermediate, and high risk of relapse. The pattern of bcr/abl PCR detection after transplant may aid in the development of trials designed to reduce the risk of relapse, or allow for early intervention in patients who fail to clear the malignant clone.
DDS is characterized by neurologic deterioration and cerebral edema which occurs after hemodialysis. To investigate the pathogenesis of DDDS, we studied the effects of rapid hemodialysis on plasma and brain electrolytes, urea, and osmolality in the rat. Forty-two hours after bilateral nephrectomy, nine uremic rats were hemodialyzed for 90 minutes against dialysate without urea (model of DDS), yielding a decrease in plasma urea from 72 +/- 2 mM to 34 +/- 2 mM (P less than 0.01) and an 8% (29 mOsm/kg) decrease in plasma osmolality. This group was compared to three control groups: 11 uremic animals dialyzed against a bath with urea added so that no fall in plasma urea occurred, and 15 uremic and 12 nonuremic animals that were not dialyzed. In animals dialyzed without urea, compared to uremic non-dialyzed animals, there was a 6% increase in brain water (3.89 +/- 0.04 liter/kg dry wt vs. 3.67 +/- 0.03, P less than 0.01) and an increase in the brain to plasma (urea) ratio (1.30 +/- 0.06 vs. 0.79 +/- 0.05, P less than 0.01). Comparison of these parameters in animals dialyzed without urea versus other control groups yielded similar results. In animals dialyzed without urea, the 53% decrease in plasma urea was associated with only a 13% decrease in brain urea content. Brain content of sodium and potassium was not significantly different among groups. Retention of brain urea despite the large decrease in plasma urea was able to account for the increased brain water observed in animals dialyzed without urea.(ABSTRACT TRUNCATED AT 250 WORDS)
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Acute lymphoblastic leukemia with eosinophilia is a rare but distinctive clinical entity. The eosinophilia in these patients can present before, concomitantly, or after the diagnosis of leukemia. Patients with this syndrome often suffer from the cardiovascular complications of severe eosinophilia, suffering excess morbidity and mortality as a result of their eosinophilia. Treatment of the eosinophilia in this syndrome consists of administration of induction chemotherapy, followed by prednisone and hydroxyurea if required for persistent eosinophilia. Eosinophilia often resolves with remission of leukemia, only to return at the time of relapse in a high percentage of cases. Patients with this syndrome characteristically have cytogenetic abnormalities involving the long arms of chromosomes 5 and 14. These cytogenetic abnormalities are not commonly seen in acute lymphoblastic leukemia and suggest that this syndrome may have a distinct pathophysiology and etiology. The affected region on chromosome 5 contains genes that control hematopoiesis, including eosinophilopoiesis. Further investigations into these cytogenetic abnormalities may provide insight into the etiology of the leukemia and eosinophilia characteristic of this syndrome.
Patient-controlled analgesia (PCA) is a concept that permits patients to administer a prescribed dose of narcotic to themselves when they experience pain. Six patients developed colonic pseudoobstruction after the use of morphine sulfate administered via a PCA infuser. Early recognition and prompt treatment make this a transient, reversible illness. Treatment includes discontinuing the use of the PCA morphine, eliminating oral intake, ensuring adequate hydration and electrolyte balance, placing a nasogastric tube, rolling the patient, and closely observing for signs and symptoms of worsening colonic distention and possible rupture.
The authors investigated habituation of the eye-blink component of the startle reflex to repeated affectively neutral tactile and auditory stimuli in nine subjects with posttraumatic stress disorder and nine controls. Each group showed rapid habituation in both tactile and auditory modalities.
The platelet membrane glycoprotein IIb X IIIa heterodimer complex (GPIIb X IIIa) is the platelet receptor for adhesive proteins, containing binding sites for fibrinogen, von Willebrand factor, and fibronectin on activated platelets. GPIIb X IIIa also appears to be a member of a family of membrane adhesive protein receptors that plays a major role in cell-cell and cell-matrix interactions. GPIb is the larger component of this platelet receptor and is composed of two disulfide-linked subunits. In this report we describe the analysis of cDNA clones for human GPIIb that were isolated from a lambda gt11 expression library prepared using RNA from HEL cells. A total of 3.3 kilobases of cDNA was sequence, revealing a continuous open reading frame encoding both GPIIb subunits. The cDNA encodes 1039 amino acids: 137 constituting the smaller subunit, 871 constituting the larger subunit, and 30 constituting an NH2-terminal signal peptide. No homology was found between the larger and smaller subunits. The smaller subunit contains a 26-residue hydrophobic sequence near its COOH terminus that represents a potential transmembrane domain. Four stretches of 12 amino acids present in the larger subunit are homologous to the calcium binding sites of calmodulin and troponin C. Northern blot analysis using HEL cell RNA indicated that the mature mRNA coding for GPIIb is 4.1 kilobases in size. A comparison of the GPIIb coding region with available cDNA sequences of the alpha-chains of the vitronectin and fibronectin receptors revealed 41% DNA homology and 74% and 63% amino acid homology, respectively. Our data establish the amino acid sequence for the human platelet glycoprotein IIb and provide additional evidence for the existence of a family of cellular adhesion protein receptors.
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