Prognostic utility of spontaneous erythroid colony formation and JAK2 mutational analysis for thrombotic events in essential thrombocythaemia.

BACKGROUND: Thrombotic events in essential thrombocythaemia (ET) are difficult to predict with current risk stratification based on age and prior history of thrombosis. AIMS: We aimed to assess the predictive value of the JAK2 V617F mutation (JAK2) and spontaneous erythroid colony (SEC) growth for the development of thrombotic events post diagnosis in patients with ET. METHODS: Consecutive patients with ET were retrospectively identified, and clinical and laboratory correlates were evaluated. Thrombotic events were categorized according to their occurrence at or prior to diagnosis (prior thrombosis), and any time post diagnosis of ET (subsequent thrombosis). JAK2 analysis was performed by allele-specific PCR on whole blood or bone marrow. RESULTS: A total of 62 patients was identified, median age 63 years; 67% (41/61) JAK2-positive and 47% (25/53) SEC-positive. Median follow-up was 33 months (range, 1 to 137). JAK2-positive patients showed a trend to increased prior thrombosis (27% vs 5%, P= 0.08), and a significant increase in the development of subsequent thrombosis (5-year event rate 31% vs 6%, P= 0.04), which persisted when stratified for a history of prior thrombosis (P= 0.04). Survival was not affected by JAK2 status. The SEC assay predicted an increased rate of baseline thrombosis (16% vs 0%, P= 0.04), but was not found to be predictive of any subsequent thrombotic events. CONCLUSIONS: Patients with ET who are JAK2-positive by whole blood allele-specific PCR appear to be at increased risk of thrombotic complications, which is independent of a prior history of thrombosis.

The impact of naturally occurring DR3 microvariants, DRw17 and DRw18, on T-cell allorecognition.

The limited amino acid sequence differences between the DR3 microvariants, DRw17 and DRw18, are found in the second variable region of the DR beta chain (residues 26 and 28) as well as in framework residues 47 and 86. Using selected responder/stimulator combinations, alloproliferative T-lymphocyte clones (TLC) were generated which recognize either a supertypic DR3-related determinant(s) or only those T-cell recognition determinants created by the four amino acids which differ between DRw17 and DRw18. Results indicate that the microvariation creates potent T-cell recognition determinants while leaving the DR3-related determinant(s) unaffected. Several TLC were generated which recognize the DRw18 molecule strongly and the DRw52c molecule weakly reflecting the sequence similarity between these molecules. In addition, one TLC was generated which recognizes DRw18 and DRw14,Dw9 but not DRw14,Dw16 molecules, a result not predicted by linear amino acid sequence comparisons. The intricate and sometimes unpredictable allorecognition patterns observed demonstrate that the molecular context of a specific amino acid sequence is as important as the actual sequence in forming a T-cell recognition site and, thus, in shaping the immune response profile of a given allele.

Experimental candidiasis in the hamster cheek pouch.

Sixty-four adult male BIO 87.20 hamsters were divided into four equal groups. Animals in three groups had 1 ml of a thick aqueous suspension of either Candida albicans (ATCC 10261), Candida albicans (UO1) or Candida tropicalis (3100, Puna Culture Collection) placed in each of their cheek pouches. The fourth group were controls. Four animals from each group were killed 1, 2, 4 and 6 weeks following treatment. Specimens were removed from all left-cheek pouches and processed routinely for light microscopy. All animals treated with strain UO1 and 35 per cent of animals treated with either 10261 or 3100 strains exhibited changes. At 1 week, the epithelium had localized areas of neutrophilic leukocyte infiltration and some small discrete micro-abscesses. At 2 weeks, most micro-abscesses were larger. At 4 weeks, most micro-abscesses involved the more superficial epithelial layers. At 6 weeks, there were only a few superficial micro-abscesses. At 4 and 6 weeks, there were areas of thickened, often parakeratinized, stratum corneum. The connective tissue adjacent to the inflamed epithelium was infiltrated by varying numbers and types of chronic inflammatory cell. Hyphal invasion of the epithelium was not found. Thus the hamster cheek pouch is a suitable site for the study of experimental candidiasis. The occurrence of both an acute and chronic inflammatory response does not support the suggestion that the pouch is an immunologically-privileged site.

Effects of chronic Candida albicans in the hamster cheek pouch.

Sixty-four adult male hamsters had a suspension of either C. albicans (UO1) or C. albicans (ATCC 10261) placed in their cheek pouches once a week for up to 9 months. Four hamsters from both experimental groups, along with two untreated control hamsters, were killed at monthly intervals after the initial inoculation. Sections taken from the hamsters and examined in the light microscope showed that all experimental pouches had some or all of the following localized changes: inflammation and increased vascularity of the connective tissue; epithelial inflammation and microabscesses; hyperkeratosis; and isolated rete ridges similar to those in control pouches. C. albicans, usually the yeast form, was present on the exposed surface and between hyperplastic keratin squames. There was no hyphal invasion of the epithelium. Rather than being a true long-term study of chronic infection by C. albicans, the changes seen were probably the result of repetitive, more short-term responses after multiple inoculations.

Working through the public disclosure process mandated by use of 21 CFR 50.24 (exception to informed consent): guidelines for success.

New Food and Drug Administration guidelines allow research to be done under an "exception to informed consent." These guidelines mandate advance public disclosure (PD) but provide no specifics for how to accomplish this task. This report outlines the history of informed consent in emergency care situations, highlights the Food and Drug Administration regulations for an exception to informed consent, and describes a stepwise approach with specific details of a PD program for a study using a blood substitute. This descriptive report can serve as a guideline for subsequent emergency care investigators in the development of a strategic plan for PD.

Serving the needs of persons with chronic mental illness: a neglected ministry.

Argues that the present disarray in services for persons with chronic mental illness opens the door for the Church to provide important and needed ministries. Describes various misconceptions and prejudices and the services church people can provide to meet the challenge.

Predicting cognitive recovery from closed head-injury in children and adolescents.

Longitudinal data from 84 head-injured children and adolescents, who were tested at three points in the first year postinjury, were analyzed to determine the best combination of demographic, injury-related, and behavioral factors predicting cognitive performance. Dependent variables were language, memory, visuomotor, and speeded performance factor scores obtained through confirmatory factor analyses of an extensive test battery. Multiple regression analyses indicated that injury severity and the existence of previous psychological, physical, or cognitive disorders were primary for predicting acute (1 month post-hospital discharge) performance for older subjects. For younger subjects, however, parental marital status was the most important correlate of acute cognitive performance. Those residing in homes with both parents fared better than children in one-parent families. At 6 months and 1 year postinjury, the older subjects who performed most poorly initially remained the most impaired. For younger children, acute cognitive standing was also an important predictor of later performance, but parental marital status remained a crucial influence on their longer-term recovery of cognitive skills.

Clinical analysis of the utility of repeat computed tomographic scan before discharge in blunt hepatic injury.

OBJECTIVES: Nonoperative management of hemodynamically stable blunt hepatic injury has emerged as an acceptable and safe treatment. Surveillance of this population's injuries is costly. As a prelude to establishing practice guidelines, the utility of repeat computed tomographic (CT) scans was investigated. METHODS: A retrospective study was conducted on 243 hepatic injuries. The CT scans of 95 patients managed nonoperatively who did not have ongoing transfusion requirements were reviewed and graded according to the American Association for the Surgery of Trauma (AAST) hepatic injury scale. Patients were grouped according to injury grade, assigned to two subgroups (patients with one CT scan versus more than one CT scan) and compared with respect to several physiologic and clinical variables. RESULTS: Statistical analysis revealed no significant difference between subgroups with the same grade of injury. No significant difference was demonstrated between subgroups' length of stay. CONCLUSIONS: No patients failed nonoperative treatment or succumbed to their injuries. Findings on repeat CT scan have not altered the decision to discharge the clinically stable patient having suffered a grade III or lower liver injury.

Trauma 24-hour observation critical path.

BACKGROUND: The 24-hour observation critical pathway for trauma is a clinical tool developed to expedite health care delivery to minimally injured patients. The use of patient care, BS, guidelines and physician-approved standing orders was implemented in a Level I trauma center. METHODS: A retrospective chart review was performed of 122 patients admitted via the emergency department between December 1, 1993, and May 31, 1994. All patients were evaluated in the emergency department by emergency medicine and trauma physicians and deemed appropriate for 24-hour observation. The information collected included patient demographics, hospital charges, injuries, length of stay, diagnostic tests, consultations, and variances from the critical pathway. RESULTS: During the 6-month study period, there were 600 trauma admissions. Of those admissions, 122 patients (20%) were evaluated in the emergency department and deemed appropriate for enrollment in the 24-hour observation pathway. The charts of these patients were reviewed. Fourteen admissions were determined inappropriate for the critical pathway because of the severity of injuries or discharge against medical advice. One hundred eight charts were evaluated further. Eighty-nine patients (80%) completed the critical pathway with a length of stay of 24 hours. CONCLUSION: The 24-hour observation critical pathway was designed and used appropriately as exemplified by an overall 80% completion rate. The critical pathway offers a mechanism to streamline care of the minimally injured trauma patient. It also serves as a quality-improvement tool for increasing efficiency, decreasing utilization of resources, and decreasing length of stay.

Outcome assessment of physiologic and clinical predictors of survival in patients after traumatic injury with a trauma score less than 5.

OBJECTIVE: To define those physiologic and clinical variables that have a positive or negative predictive value in discriminating survivors from nonsurvivors with traumatic injuries and a Trauma Score of 5 or less. METHODS: A retrospective review of 2,622 trauma patients transported by an air medical service from the scene of injury to a Level I trauma center was performed. Demographic, physiologic, and clinical variables were evaluated. RESULTS: One hundred thirty-six patients were studied; 14 patients survived trauma resuscitation. Survivors had statistically significant improvement in the Glasgow Coma Scale from the field to arrival in the emergency room. Revised Trauma Score, probability of survival, pulse, respiratory rate, cardiac rhythm, central nervous system activity, and signs of life were statistically more favorable in survivors. CONCLUSION: In patients who survived to discharge, signs of central nervous system activity in the field was a positive predictor of survival, and severe head injury served as a negative predictor of survival.

Prehospital blood transfusion versus crystalloid alone in the air medical transport of trauma patients.

INTRODUCTION: Differences in prehospital resuscitation measures and outcomes of trauma patients transported by two air medical programs were assessed comparing the prehospital administration of crystalloid only (Group A) with the administration of 2 liters of crystalloid followed by blood (Group B). METHODS: A 1-year retrospective review of flight and hospital records of patients taken to Level I trauma centers by two separate air medical programs was completed. Physiologic variables, total fluids infused, and flight times were compared. RESULTS: Thirty-one patients (Group A) received crystalloids in flight, and 17 patients received in-flight blood (Group B). No statistical differences were found between the two groups when comparing age, ISS, PS, RTS, GCS, survival, and total fluid volume. Group B had statistically greater mean flight times compared with Group A (P < .05). A difference was demonstrated between groups A and B in pH and HCO3 measurements (P < .05), with Group B presenting in a more acidotic state on admission to the hospital. CONCLUSION: Patients with lengthy flight times, despite the administration of blood products, presented to the trauma center more acidotic than trauma patients receiving only crystalloid. The true impact of blood products on outcome could not be demonstrated because of statistical differences in flight times between the groups. A multicenter study matching flight times, head injury status, and flight type of assess benefit of prehospital utilization of blood products is warranted.

Selective hepatic arterial embolization of grade IV and V blunt hepatic injuries: an extension of resuscitation in the nonoperative management of traumatic hepatic injuries.

BACKGROUND: Recognizing the significant mortality and complications inherent in the operative management of blunt hepatic injuries, hepatic arterial embolization was evaluated as a bridge between operative and nonoperative interventions in patients defined as hemodynamically stable only with continuous resuscitation. METHODS: Seven of 11 patients with grade IV or V hepatic injuries identified by computed tomography underwent hepatic arterial embolization. A prospective evaluation of hepatic embolization based on subsequent hemodynamic parameters was assessed by matched-pair analysis. A summary of this study population's demographic data and outcomes is presented, including age, Glasgow Coma Scale score, Injury Severity Score, Revised Trauma Score, computed tomography grade, intensive care unit and hospital length of stay, transfusion requirements, complications, and mortality. RESULTS: No statistical difference was demonstrated between pre-embolization and postembolization hemodynamics and volume requirements. After embolization, however, continuous resuscitation was successfully reduced to maintenance fluids. Hepatic embolization was the definitive therapy for all seven patients who underwent embolization. CONCLUSION: Results of this preliminary investigation suggest that hepatic arterial embolization is a viable alternative bridging the therapeutic options of operative and nonoperative intervention for a subpopulation of patients with hepatic injury.