Elimination of alloantibodies by immunoablative high-dose cyclophosphamide.

BACKGROUND: Alloimmunization is a major problem for patients being considered for solid organ transplantation and in patients who require blood transfusion support. We previously demonstrated that high-dose cyclophosphamide (200 mg/kg) without hematopoietic stem cell transplantation leads to durable complete remissions in aplastic anemia and other autoimmune disorders. We now examine the ability of high-dose cyclophosphamide to eliminate alloreactivity. METHODS: IgG-specific antibodies to HLA class I were assayed using enzyme-linked immunosorbent assays in 18 consecutive patients with severe aplastic anemia before and after treatment with high-dose cyclophosphamide. RESULTS: Anti-HLA antibodies were detected before or shortly after therapy in 5 of the 18 patients studied. Complete remission of aplastic anemia was achieved in four of these five patients. High-dose cyclophosphamide markedly reduced anti-HLA antibody titers in these four patients; they were completely eradicated in three patients. Only one patient did not achieve significant reduction in the alloantibody titer after high-dose cyclophosphamide. CONCLUSIONS: High-dose cyclophosphamide without stem cell transplantation can eradicate HLA-specific alloantibody.

Acute bleeding and thrombocytopenia after bone marrow transplantation.

The relationship between hemorrhage and low platelet count was first established in patients with acute leukemia, and has been widely applied to thrombocytopenic patients, including BMT patients. Yet, the role of thrombocytopenia in bleeding post BMT has not been systematically studied. We evaluated the risk of bleeding and outcome associated with thrombocytopenia in BMT patients who had prophylactic platelet transfusions at a trigger of 20 x 10(9)/l. Thrombocytopenia was investigated in 321 patients with moderate or severe bleeding (BLD), and in a matched comparison group of 287 patients who did not bleed (NBLD). Profound thrombocytopenia (< or = 10 x 10(9)/l) was found in 8.6% of the BLD patients during the week before the bleeding onset, significantly more frequent than in NBLD patients (2.1% to 4%, P < 0.02), during weeks 2 to 6 post BMT (the period when 75% of the bleeding initiated). On the first day of bleeding, platelet counts < or = 10 x 10(9)/l were found in 13.5%, 11-20 x 10(9)/l in 20.4%, and > 20 x 10(9)/l in 66.1% of all episodes. Overall survival in BLD patients was not associated with the severity of thrombocytopenia before bleeding onset. Severity of thrombocytopenia was significantly associated with reduced survival in NBLD patients. We concluded that bleeding post BMT was significantly associated with thrombocytopenia, but the attributable risk of bleeding from profound thrombocytopenia was not large. Thrombocytopenia may be an important clinical sign in NBLD patients, and should be further explored in relation to acute toxicities other than bleeding.

Acute bleeding after allogeneic bone marrow transplantation: association with graft versus host disease and effect on survival.

BACKGROUND: Hemorrhagic complications are frequently implicated clinically for the high morbidity and mortality of acute graft versus host disease (GVHD), however, only few reports characterize the incidence and timing of bleeding in relation to GVHD, and essentially no study has quantified the effect of bleeding on survival of allogeneic patients with GVHD. This study examines the association of bleeding with acute GVHD and the effect of both complications on survival. METHODS: A total of 463 allogeneic patients transplanted at the Johns Hopkins Hospital, were included in the study. Bleeding evaluation was based on daily scores of intensity and blood transfusions. All bleeding sites were recorded. GVHD staging was defined by the extent of rash, serum bilirubin, diarrhea, and confirmatory histology. RESULTS: The incidence of GVHD was 27.4%, bleeding occurred in 40.2%. The incidence of bleeding was higher in patients with GVHD as compared with non-GVHD, and correlated with GVHD severity. The higher bleeding incidence in GVHD was due to gastrointestinal hemorrhage, hemorrhagic cystitis, and pulmonary hemorrhage. While the majority of bleeding (51/75) in non-GVHD patients initiated within 30 days after bone marrow transplantation (BMT), only 32.3% (21/65) of the bleeding in the GVHD group initiated within 30 days, and the risk for bleeding continued until day 100. Bleeding was a late event compared to GVHD, however, most bleeding episodes were associated with active GVHD. Both GVHD and bleeding were individually associated with reduced survival, with profound additive adverse effect: median survival in 221 nonbleeding non-GVHD was >83.2 months, GVHD nonbleeding (39 patients) had median of 10.6 months, bleeding non-GVHD (99 patients) had median of 4.3 months, and median survival of the GVHD bleeding group (85 patients) was 3.2 months. CONCLUSIONS: Our results support an association of bleeding with acute GVHD, suggesting that GVHD is a risk factor for bleeding after BMT. The occurrence of bleeding clearly identified poor outcome subgroup within GVHD, suggesting further evaluation for clinical application of bleeding in the assessment of GVHD severity.

Acute bleeding after bone marrow transplantation (BMT)- incidence and effect on survival. A quantitative analysis in 1,402 patients.

Acute bleeding after bone marrow transplantation (BMT) was investigated in 1,402 patients receiving transplants at Johns Hopkins Hospital between January 1, 1986 and June 30, 1995. Bleeding categorization was based on daily scores of intensity used by the blood transfusion service. Moderate and severe episodes were analyzed for bleeding sites. Analysis of the cause of death and the interval of the bleeding episode to outcome endpoints was recorded. Survival estimates were computed for 1,353 BMT patients. The overall incidence was 34%. Minor bleeding was seen in 10.6%, moderate bleeding was seen in 11.3%, and severe bleeding was seen in 12% of all patients. Fourteen percent of patients had moderate or severe gastrointestinal hemorrhage, 6.4% had moderate or severe hemorrhagic cystitis, 2.8% had pulmonary hemorrhage, and 2% had intracranial hemorrhage. Sixty-one percent had 1 bleeding site and 34.4% had more than 1 site. Moderate and severe bleeding was more prevalent in allogeneic (31%) and unrelated patients (62.5%) compared with autologous patients (18.5%). Significant distribution of incidence was found among the different diagnoses, but not by disease status in acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, Hodgkin's disease, and non-Hodgkin's lymphoma. Bleeding was associated with significantly reduced survival in allogeneic, autologous, and unrelated BMT and in each disease category except multiple myeloma. Survival was correlated with the bleeding intensity, bleeding site, and the number of sites. Although close temporal association was evident to mortality, bleeding was recorded as the cause of death in only the minority of cases compared with other toxicities after BMT (graft-versus-host disease, infections, and preparative regimen toxicity). Acute bleeding is a common complication after BMT that is profoundly associated with morbidity and mortality. Although bleeding was not a direct cause of death in the majority of cases, it has a potential prognostic implication as a predictor of poor outcome in clinical assessment of patients after BMT.

Predicting the DSM-V.

Using regression estimates based upon data about past editions of the DSM, we predict various features of the DSM-V. Included in these predictions are the date of publication, number of pages, total number of categories, number of categories defined using diagnostic criteria, total number of diagnostic criteria, color of the manual, who will be in charge of the task force that creates the DSM-V, and revenues generated by the DSM-V. This article ends with comments on the changes in the editions of the DSMs and an analogy to the Sorcerer's Apprentice.

A test of exercise analgesia using signal detection theory and a within-subjects design.

Evidence for the existence of exercise-induced analgesia has been weak, inconsistent, or anecdotal. The present study addresses criticisms of previous research by using a signal-detection analysis of pain perception in a within-subjects, repeated-measures research design with 22 endurance athletes who exercised in a naturalistic setting. Analysis showed discriminability measures from the lower intensities of a radiant-heat pain-perception task were significantly lower after exercise than the subjects' discriminability after a no-exercise period. This is consistent with discriminability decreases seen in studies of subjects who are under the influence of analgesic chemicals such as morphine and nitrous oxide. Discriminability differences were not seen in this study at the higher intensities of the stimulus, suggesting that exercise generates perceptual changes that may not reach pain-mediating levels. Visual analogue data suggest cognitive and motivational factors also play a role in report of pain after exercise.

Personality disorders: an overview for the physician.

Personality disorders are common clinical syndromes that often go unrecognized in medical practice. Because patients with personality disorders receive care in all clinical settings, physicians could profit from a heightened awareness of the personality psychopathology of their patients and its impact on medical practice. Personality traits are universal and describe the "normal" range of behavior, while personality disorders are characterized by enduring maladaptive patterns. The etiology of personality disorders is multifactorial. Physician awareness of the multiple manifestations of specific personality disorders is helpful in matching the proper interventions to appropriate patients. Although management is symptomatically palliative rather than curative, physicians and patients alike can benefit from appropriate recognition and treatment of personality disorders.

Sadistic and self-defeating personality disorder criteria in a rural clinic sample.

A sample of 176 outpatients at a mental health clinic in rural southern Georgia were rated for the presence or absence of the DMS-III-R sadistic and self-defeating personality disorder criteria. On the basis of these ratings, 48 patients met the criteria for sadistic (n = 14) and self-defeating (n = 41). Surprisingly, half of the patients who met the sadistic criteria also fulfilled the self-defeating criteria. A factor analysis failed to divide the criteria cleanly into sadistic and self-defeating subsets.

Physical and psychosocial correlates of test-retest isometric torque variability in patients with chronic low back pain.

Variability in trunk torque production has been suggested as a means of detecting submaximal effort in the assessment of chronic low back pain. Several investigations question the validity of using torque variability to detect submaximal efforts in patients with back injuries. However, few investigations have studied the correlates of text-retest torque variability in clinical populations. The present study investigated psychological distress, disability/flexibility/pain, and symptom magnification correlates of test-retest torque variability in chronic low back pain patients. Contrary to previous studies, psychological distress, tendency to report symptoms, and pain were negatively correlated with measures of torque variability. The findings indicate the potential for psychological variables to influence torque production, but on the whole provide little strong support for the use of test-retest torque variability as a means of detecting submaximal performance.

Septic reactions to platelet transfusions. A persistent problem.

OBJECTIVE: To determine the medical and laboratory characteristics of bacteremia secondary to transfusion of microbiologically contaminated platelet concentrates. DESIGN: Febrile transfusion reactions were prospectively monitored over 42 months. Units involved in reactions were evaluated with Gram's stain and culture tests. SETTING: Comprehensive cancer center. PATIENTS: Patients receiving platelet transfusions for thrombocytopenia secondary to bone marrow failure. RESULT: Seven cases of transfusion-associated sepsis were observed. Multidonor platelet products stored for 5 days resulted in an incidence of sepsis five times higher than those stored for 4 days or less (P less than .01). Investigation indicates that contamination most likely occurred at the time of blood collection. Clinically, septic reactions were associated with greater temperature elevations (average increase, 2.0 degrees C) than febrile reactions to sterile products. CONCLUSIONS: Contamination of platelet concentrates remains a significant clinical problem. Septic episodes may be reduced by transfusion of platelets with shorter storage intervals.

Suggested guidelines for including or excluding categories in the DSM-IV.

A set of guidelines is proposed for the possible inclusion or exclusion of diagnostic categories in the DSM-IV. For possible inclusion, a new category should meet all of the following five guidelines: adequate literature, specified diagnostic criteria, acceptable interclinician reliability, evidence that the criteria forms a syndrome, and differentiation from other categories. For possible exclusion, a category should possess an inadequate literature, extremely low coverage, or evidence of diagnostic bias. None of the exclusionary guidelines would be invoked if the category refers to a demonstrable disease.

Masochistic personality disorder. A prototype analysis of diagnosis and sex bias.

The Work Group of the American Psychiatric Association to revise DSM-III in 1985 proposed a new personality disorder titled Masochistic Personality Disorder (MPD). This study concerns the clinical relevance and possible sex bias of MPD. The study was performed with clinicians who analyzed 15 case histories, five of which represented masochistic personality. The results led to the rejection of two hypotheses: a) masochistic personalities can be subsumed under existing DSM-III categories and b) there is a sex bias in the diagnostic use of MPD.

Child molestation and pedophilia. An overview for the physician.

Child sexual abuse is a serious, pervasive problem with clinical, social, moral, and legal implications. Between 100,000 and 500,000 children in the United States are thought to be sexually molested annually. Physicians in all specialties may detect sexual exploitation of youngsters and are mandated to report such cases. Failure to diagnose child molestation and pedophilia and to treat their cause can have serious, long-lasting consequences for innocent victims and continued distress for the perpetrator and for the professional who missed the diagnosis. A single child molester may commit hundreds of sexual acts on hundreds of children. The etiology of paraphilic syndromes is multifactorial. There are substantial differences among sexual abusers of children in their personalities and psychopathologies. Although available interventions are symptomatically palliative rather than curative, many pedophiles can benefit from appropriate treatment. Primary prevention may be the key to reducing the frequency of child sexual abuse.

Sexual maturity as a criterion for classification of phallometric stimulus slides.

With the acceptance of behavior modification techniques in the 1970's as the standard modality of treatment of sex offenders, the ability to diagnose the paraphilic arousal patterns became of primary importance. The use of the penile plethysmograph in the assessment of sex offenders is regarded as the most accurate measure of these sexual arousal patterns. This method measures the vasocongestive engorgement of the penile corporea while the offender is exposed to deviant and nondeviant sexual stimuli. The stimuli may be slides of nude males and females of varying ages, audiotaped descriptions of erotic scenarios or videotaped scenes of sexual interaction. Researchers who have used slides to determine the age and gender preference of the sex offenders have typically categorized the slides in arbitrarily established age categories that have varied from one research study to another. The use of age as a criterion does not take into account the variation in growth and maturation among children and adolescents. To increase reliability and standardization of research techniques, the authors propose that the stages of sexual maturity as set forth by Tanner (1962, 1978) be used in lieu of age.