Pretransplant CD4 Count Influences Immune Reconstitution and Risk of Infectious Complications in Human Immunodeficiency Virus-Infected Kidney Allograft Recipients.

In current practice, human immunodeficiency virus-infected (HIV(+) ) candidates with CD4 >200 cells/mm(3) are eligible for kidney transplantation; however, the optimal pretransplant CD4 count above this threshold remains to be defined. We evaluated clinical outcomes in patients with baseline CD4 >350 and <350 cells/mm(3) among 38 anti-thymocyte globulin (ATG)-treated HIV-negative to HIV(+) kidney transplants performed at our center between 2006 and 2013. Median follow-up was 2.6 years. Rates of acute rejection and patient and graft survival were not different between groups. Occurrence of severe CD4 lymphopenia (<200 cells/mm(3) ), however, was more common among patients with a baseline CD4 count 200-349 cells/mm(3) compared with those transplanted at higher counts (75% vs. 30% at 4 weeks [p = 0.04] and 71% vs. 5% at 52 weeks [p = 0.001], respectively, after transplant). After adjusting for age, baseline CD4 count of 200-349 cells/mm(3) was an independent predictor of severe CD4 lymphopenia at 4 weeks (relative risk [RR] 2.6; 95% confidence interval [CI] 1.3-5.1) and 52 weeks (RR 14.3; 95% CI 2-100.4) after transplant. Patients with CD4 <200 cells/mm(3) at 4 weeks had higher probability of serious infections during first 6 months after transplant (19% vs. 50%; log-rank p = 0.05). These findings suggest that ATG must be used with caution in HIV(+) kidney allograft recipients with a pretransplant CD4 count <350 cells/mm(3) .

Glutathione S-transferase iso-enzymes in perfusate from pumped kidneys are associated with delayed graft function.

Accurate and reliable assessment tools are needed in transplantation. The objective of this prospective, multi-center study was to determine the associations of the alpha and pi iso-enzymes of glutathione S-transferase (GST), measured from perfusate solution at the start and end (base and post) of kidney allograft machine perfusion, with subsequent delayed graft function (DGF). We also compared GST iso-enzyme perfusate levels from discarded versus transplanted kidneys. A total of 428 kidneys were linked to outcomes as recorded by the United Network of Organ Sharing. DGF, defined as any dialysis in the first week of transplant, occurred in 141 recipients (32%). Alpha- and pi-GST levels significantly increased during machine perfusion. The adjusted relative risks (95% confidence interval) of DGF with each log-unit increase in base and post pi-GST were 1.14 (1.0-1.3) and 1.36 (1.1-1.8), respectively. Alpha-GST was not independently associated with DGF. There were no significant differences in GST values between discarded and transplanted kidneys, though renal resistance was significantly higher in discarded kidneys. We found pi-GST at the end of machine perfusion to be independently associated with DGF. Further studies should elucidate the utility of GST for identifying injured kidneys with regard to organ allocation, discard and recipient management decisions.

A case of human intramuscular adrenal gland transplantation as a cure for chronic adrenal insufficiency.

Intramuscular endocrine gland transplantation has been well described as it pertains to parathyroid autotransplantation; however, transplantation of the adrenal gland is less well characterized. While adrenal autotransplantation in the setting of Cushing's disease has been described, intramuscular adrenal allotransplantation as a cure for adrenal insufficiency to our knowledge has not been previously carried out. Current treatment for adrenal insufficiency leaves patients without diurnal variation in cortisol release and susceptible to the detrimental effects of chronic hypercortisolism. We describe here the case of a 5-year-old girl with renal failure who had adrenal insufficiency following fulminant meningococcemia that led to requirements for both stress-dose steroid and mineralocorticoid replacement. Ten months after the onset of her disease, she received a simultaneous renal and adrenal gland transplant from her mother. The adrenal gland allograft was morselized into 1 mm(3) segments and implanted into three 2 cm pockets created in her rectus abdominis muscle. Three years after surgery, her allograft remains fully functional, responding well to adrenocorticotropin hormone stimulation and the patient does not require any steroid or mineral-corticoid supplementation. We believe this case represents the first description of successful functional intramuscular adrenal allograft transplantation with long-term follow up as a cure for adrenal insufficiency.

Recombinant tissue-type plasminogen activator in the treatment of acute renal artery thrombosis after kidney transplantation.

Acute arterial thrombosis is an uncommon but potentially devastating consequence of kidney transplantation. Early recognition followed by thrombectomy may salvage the graft. We present a case of acute renal artery thrombosis after a living-related kidney transplant with successful treatment with operative thrombectomy and intraarterial infusion of recombinant tissue-type plasminogen activator.

Hypothermic machine preservation in human liver transplantation: the first clinical series.

Hypothermic machine perfusion (HMP) is widely used to preserve kidneys for transplantation with improved results over cold storage (CS). To date, successful transplantation of livers preserved with HMP has been reported only in animal models. In this, the first prospective liver HMP study, 20 adults received HMP-preserved livers and were compared to a matched group transplanted with CS livers. HMP was performed for 3-7 h using centrifugal perfusion with Vasosol solution at 4-6 degrees C. There were no cases of primary nonfunction in either group. Early allograft dysfunction rates were 5% in the HMP group versus 25% in controls (p = 0.08). At 12 months, there were two deaths in each group, all unrelated to preservation or graft function. There were no vascular complications in HMP livers. Two biliary complications were observed in HMP livers compared with four in the CS group. Serum injury markers were significantly lower in the HMP group. Mean hospital stay was shorter in the HMP group (10.9 +/- 4.7 days vs. 15.3 +/- 4.9 days in the CS group, p = 0.006). HMP of donor livers provided safe and reliable preservation in this pilot case-controlled series. Further multicenter HMP trials are now warranted.

Communication deviance in the families of schizophrenics: a comment on the misuse of analysis of covariance.

Serious contradictions in recent research programs concerning communication anomalies in parents of schizophrenics have been generated by invalid statistical analyses. The method of analysis used, the analysis of covariance, can lead to erroneous conclusions in the context of these studies, and thus, other means must be sought for bringing these important research programs into common focus.

Treatment of Strongyloides stercoralis hyperinfection-associated septic shock and acute respiratory distress syndrome with drotrecogin alfa (activated) in a renal transplant recipient.

We report a case of Strongyloides stercoralis hyperinfection syndrome in a renal transplant recipient complicated by septic shock, acute respiratory distress syndrome, and Klebsiella pneumoniae superinfection. The patient was treated successfully with drotrecogin alfa (activated), parenteral ivermectin, albendazole, and piperacillin/tazobactam. This outcome suggests that drotrecogin alfa (activated) may be useful therapy for transplant recipients who develop severe sepsis or septic shock secondary to potentially lethal opportunistic infections.

Parental affective style and the treatment of schizophrenia. Predicting course of illness and social functioning.

In a randomized controlled study, the affective style (AS) of parents of schizophrenics in clinic-based individual treatment groups and home-based family treatment groups was compared prior to treatment and again three months after treatment had begun. Affective style is an index reflecting the quality of the family emotional climate, measured from face-to-face discussion. Pretherapy and posttherapy measures of negative AS were significantly predictive of relapse within the nine-month treatment period for patients in individual treatment. In addition, for both treatment groups, a negative AS pattern at the posttherapy reassessment was significantly associated with decreased patient social functioning, reduced ability of the family to absorb the family intervention, and lower capacity of the family to cope with everyday family stresses. The results suggest that AS is an important intrafamilial attribute, with implications for treatment strategy and planning.

Family factors and the course of bipolar affective disorder.

Measures of family attitudes (expressed emotion [EE]) and interactional behaviors (affective style [AS]), both of which have been found to predict relapse in schizophrenia, were obtained from key relatives of 23 hospitalized recently manic bipolar patients. Patients were then followed up for a period of nine months after hospital discharge and rated on measures of clinical course, social adjustment, and medication compliance. Levels of intrafamilial EE and AS were found to predict likelihood of patient relapse at follow-up, especially when used as conjoint predictors of patient outcome status. Levels of AS also predicted degree of social adjustment at follow-up. The predictive relationships observed were independent of patient medication compliance, treatment regimen, baseline symptoms, demographics, and illness history. Results suggest that the emotional atmosphere of the family during the postdischarge period may be an important predictor of the clinical course of bipolar disorder.

Neurocognitive vulnerability, interpersonal criticism, and the emergence of unusual thinking by schizophrenic patients during family transactions.

BACKGROUND: This study examined whether the combination of patients' neurocognitive deficits and criticism by others would predict the emergence of patients' unusual thinking during stressful family transactions. METHODS: When clinically stable, 41 patients with recent-onset schizophrenia completed 2 versions of a visual vigilance task, the Continuous Performance Test (CPT). One CPT emphasized early perceptual processing, while the other stressed immediate, working memory. On a separate occasion, patients and family members participated in a 20-minute interaction in which the number of relatives' criticisms and patients' unusual thoughts was assessed. RESULTS: In a hierarchical regression model, after entering performance on the CPT demanding immediate, working memory, and the number of criticisms by family members, the interaction of CPT performance and criticism significantly predicted the number of patients' unusual thoughts during the family session (r(2) change = 0.09; P =.03). Post hoc analyses revealed that the number of criticisms and odd thoughts correlated significantly (r = 0.59, P =. 03) for patients who had poor memory-load CPT performance, but were unrelated (r = -0.07) for patients who did well on the memory-load CPT. The CPT emphasizing early visual processing, either alone or in combination with interpersonal criticism, did not predict the number of patients' unusual thoughts during the interaction. CONCLUSION: The results suggest that the combination of patients' working memory deficits and interpersonal criticism jointly predicts psychotic thinking, consistent with a model of schizophrenia that emphasizes the interaction of neurocognitive vulnerability and psychosocial stress factors. Arch Gen Psychiatry. 2000;57:1174-1179.

Parental transactional style deviance as a possible indicator of risk for schizophrenia.

The presence of a pattern of parental transactional style deviance on the Thematic Apperception Test (TAT) (a significant attribute of parents of offspring with schizophrenia spectrum disorders) was used to identify a group of disturbed nonpsychotic adolescents hypothesized to be at high risk for subsequently developing schizophreniform psychopathology. High-risk male adolescents came from two symptom groups, withdrawn adolescents and adolescents in active family conflict, which are symptom patterns similar to the premorbid pictures of two schizophrenia subtypes. High-risk parents also tended to show transactional style deviance in direct interaction with their child and in a written statement describing their child's problem. The degree of risk was significantly related to the amount of therapy in which the family was subsequently engaged and, at a four-year follow-up, to the level of adjustment of the adolescents seen earlier in the project.

Drug and family therapy in the aftercare of acute schizophrenics.

After a brief inpatient hospitalization, 104 acute, young schizophrenics, stratified by premorbid adjustment, were randomly assigned to one of four aftercare conditions for a six-week controlled trial. Conditions involved one of two dose levels of fluphenazine enanthate (1 ml or 0.25 ml) and presence or absence of crisis-oriented family therapy. Relapses during the six-week period and at six-month follow-up were least in patients who received both high-dose and family therapy (0%) and greatest (48%) in the low-dose-no therapy group. Brief Psychiatric Rating Scale symptom ratings disclosed a significant family therapy effect at six weeks that was sustained at six months only for therapy patients originally receiving the high drug dose. Numerous interactions were found between premorbid adjustment status and response to the two treatment conditions.

Parental communication deviance and affective style. Predictors of subsequent schizophrenia spectrum disorders in vulnerable adolescents.

In an attempt to assess the contributory role of family factors to the development of schizophrenia-like disorders, measures of parental communication deviance and affective styles of communication were obtained for a sample of families of disturbed but nonpsychotic adolescents. Outcome was assessed five years later. Absence of a pathologic affective style was associated with a benign outcome, but neither parental variable alone allowed precise identification of the schizophrenia-spectrum cases. However, an index using a combination of both variables was statistically predictive of subsequent psychiatric status at follow-up. Thus, adolescents whose parents had both a pathologic affective style of communication and a high level of communication deviance had schizophrenia-like disorders develop in young adulthood. Adolescents of parents who had both lower levels of communication deviance and a benign affective style had offspring with healthier outcomes.

Depressive symptoms in the early course of schizophrenia: relationship to familial psychiatric illness.

OBJECTIVE: This study examined the relation between the presence of depressive symptoms in schizophrenic patients with a recent first psychotic episode and affective disorders among their relatives. METHOD: Data on depressive symptoms in 70 patients with schizophrenia diagnosed according to the DSM-III-R criteria, who had had a recent first psychotic episode, and psychiatric diagnostic information on 293 of their first-degree and 674 of their second-degree relatives were collected. Depressive symptoms in the schizophrenic probands were examined at the index psychotic episode (at study entry) and systematically over a 1-year follow-through period. The majority of first-degree family members were interviewed in person with the use of semistructured diagnostic interviews. RESULTS: The linear regression findings confirmed the hypothesis that depressive symptoms in the early course of schizophrenia are associated with a family history of unipolar affective illness. CONCLUSIONS: Because depression in the patients was associated with a family history of depression, this suggests that depression in schizophrenia is not solely either a reaction to having had a psychotic episode or part of the recovery process. The findings are consistent with a model in which a familial genetic liability to affective disorder, when present, is viewed a s exerting a modifying influence on the patient's schizophrenic illness to increase expression of depressive symptoms.

Further data concerning the relation between premorbid adjustment and paranoid symptomatology.

This study examines the relationship between premorbid adjustment and paranoid status in acute schizophrenia. In order to avoid limitations of previous studies, premorbid adjustment (based on the UCLA Social Attainment Scale) was considered at five levels instead of the usual binary classification (good vs. poor) and paranoid symptomatology (using the Venables and O'Connor Scale) was considered rather than paranoid diagnosis. In a sample of 112 first lifetime admission schizophrenics, a positive linear relationship was found between premorbid adjustment and paranoid symptoms. Definite paranoid symptomatology was largely absent at the lowest levels of premorbidity and increased progressively with more adequate premorbid adjustment. The one exception to this linear trend was noted for the highest (most superior) level of premorbid adjustment where an increase of nonparanoid cases was observed.

Psychosocial issues.

This article uses a version of the vulnerability-stress model to examine psychosocial factors related to the onset, course, and treatment of schizophrenia. High-risk studies, most of which study offspring of a schizophrenic parent, suggest that signs of vulnerability to the disorder may emerge in early to middle childhood in neuromotor integration, attentional and information-processing abilities, and deviant social behavior. It is still not clear that these markers are specific to the subsequent development of schizophrenia. The evidence for stressful family relationships as potentiators of the disorder in vulnerable off-spring is also reviewed. Although few studies are available that bear directly on this issue, the preliminary evidence suggests that further investigation is warranted. Stressors, particularly those arising from within the family, are also examined as they relate to the course of schizophrenia. The data on expressed emotion (EE) have been replicated more often than not, although the origins of high EE attitudes are not precisely understood. These attitudes do not arise as reactions to the form or severity of a relative's disorder, but they may relate to the length of time between initial onset of the disorder and first hospitalization. Family-based intervention programs, overlaid on regular antipsychotic drug treatment, appear to reduce the risk for relapse in the short-term. At least one of the mechanisms of action of these programs is to reduce the negative affective climate in the family.

The UCLA High-Risk Project.

The UCLA High Risk Project studied a cohort of 64 families over a 15-year followup period. At entry to the study, the families each contained one adolescent who was having behavioral difficulties for whom help was sought from a psychological clinic. Two criteria of the degree of risk for schizophrenia were devised initially, one based on the form of the adolescent's problem and the other on the parental attributes of communication deviance (CD), affective style (AS), and expressed emotion (EE). It was hypothesized that schizophrenia would be the likely outcome when certain patterns of adolescent disturbance and negative communicational and affective patterns were present in the family. The index offspring of 54 of the 64 families were successfully followed up over the 15-year period (mean age = 30 at last followup), and blind psychiatric diagnoses were done. Contrary to the initial hypothesis, the form of the adolescent problem had limited prognostic value; however, the combination of CD and AS correctly identified the overwhelming number of cases who developed schizophrenia and related disorders. CD did even better if the dependent variable was the risk for schizophrenia spectrum disorder in any offspring in the family.

Therapist ratings of achievement of objectives in psychotherapy with acute schizophrenics.

Therapist ratings of patients' achievement of objectives in psychotherapy were used to examine the impact of drugs on psychotherapy, to identify attributes of patients who achieve therapy objectives, and to assess the importance of the implementation of a crisis-oriented model of therapy. Patients were part of a project investigating the long-acting phenothiazine fluphenazine enanthate and crisis-oriented family therapy in a 6-week program of aftercare treatment for briefly hospitalized first admission acute schizophrenics. The 44 patients in this study were randomly assigned to the psychotherapy condition and to either a high or low dosage of phenothiazines. Therapist ratings of the achievement of therapy objectives were significantly related to independent ratings on two outcome measures, the Global Assessment Scale and the Brief Psychiatric Rating Scale (BPRS) factor Thought Disorder, at 6-month followup. Analyses of predictors of the achievement of therapy objectives revealed significant interactions between drug level and Venables and O'Connor ratings of paranoid symptomatology among good permorbid patients and between drug level and BPRS ratings of Hostility for the entire sample.

Childhood-onset schizophrenia: a followup study.

This article is an overview of our studies of childhood-onset schizophrenia. Data are presented demonstrating that (1) the majority of the sample showed continuing schizophrenia as they progressed through adolescence; (2) there was considerable variability in outcome, defined by global adjustment scores, with 56 percent of the sample showing improvement in functioning during a 2- to 7-year followup period and the other 44 percent showing minimal improvement or a deteriorating course; (3) schizophrenia in childhood could be diagnosed by the same criteria used for adults and was associated with severe dysfunction; and (4) some intrafamilial attributes found to be associated with schizophrenia in adults were also associated with schizophrenia in children, but there were some differences in the family environmental correlates of childhood- and later-onset schizophrenia. These data are consistent with the hypothesis that childhood- and later-onset schizophrenia represent the same illness or illnesses. Additional research is needed, however, to clarify the etiologic and clinical significance of the atypical early onset in childhood cases.