Sue Dimiceli

A Genomic Screen of Autism: Evidence for a Multilocus Etiology

We have conducted a genome screen of autism, by linkage analysis in an initial set of 90 multiplex sibships, with parents, containing 97 independent affected sib pairs (ASPs), with follow-up in 49 additional multiplex sibships, containing 50 ASPs. In total, 519 markers were genotyped, including 362 for the initial screen, and an additional 157 were genotyped in the follow-up. As a control, we also included in the analysis unaffected sibs, which provided 51 discordant sib pairs (DSPs) for the initial screen and 29 for the follow-up. In the initial phase of the work, we observed increased identity by descent (IBD) in the ASPs (sharing of 51.6%) compared with the DSPs (sharing of 50.8%). The excess sharing in the ASPs could not be attributed to the effect of a small number of loci but, rather, was due to the modest increase in the entire distribution of IBD. These results are most compatible with a model specifying a large number of loci (perhaps >/=15) and are less compatible with models specifying </=10 loci. The largest LOD score obtained in the initial scan was for a marker on chromosome 1p; this region also showed positive sharing in the replication family set, giving a maximum multipoint LOD score of 2.15 for both sets combined. Thus, there may exist a gene of moderate effect in this region. We had only modestly positive or negative linkage evidence in candidate regions identified in other studies. Our results suggest that positional cloning of susceptibility loci by linkage analysis may be a formidable task and that other approaches may be necessary.

A Phase II, double-blind, randomized, placebo-controlled clinical trial of tgAAVCF using maxillary sinus delivery in patients with cystic fibrosis with antrostomies

tgAAVCF, an adeno-associated cystic fibrosis transmembrane conductance regulator (CFTR) viral vector/gene construct, was administered to 23 patients in a Phase II, double-blind, randomized, placebo-controlled clinical trial. For each patient, a dose of 100,000 replication units of tgAAVCF was administered to one maxillary sinus, while the contralateral maxillary sinus received a placebo treatment, thereby establishing an inpatient control. Neither the primary efficacy endpoint, defined as the rate of relapse of clinically defined, endoscopically diagnosed recurrent sinusitis, nor several secondary endpoints (sinus transepithelial potential difference [TEPD], histopathology, sinus fluid interleukin [IL]-8 measurements) achieved statistical significance when comparing treated to control sinuses within patients. One secondary endpoint, measurements of the anti-inflammatory cytokine IL-10 in sinus fluid, was significantly (p < 0.03) increased in the tgAAVCF-treated sinus relative to the placebo-treated sinus at day 90 after vector instillation. The tgAAVCF administration was well tolerated, without adverse respiratory events, and there was no evidence of enhanced inflammation in sinus histopathology or alterations in serum-neutralizing antibody titer to adeno-associated virus (AAV) capsid protein after vector administration. In summary, this Phase II trial confirms the safety of tgAAVCF but provides little support of its efficacy in the within-patient controlled sinus study. Various potentially confounding factors are discussed.

Effects of Supportive-Expressive Group Therapy on Survival of Patients With Metastatic Breast Cancer A Randomized Prospective Trial

One hundred twenty-five women with confirmed metastatic (n 5 122)or locally recurrent (n 5 3) breast cancer were randomly assigned either to the sup-portive-expressive group therapy condition (n 5 64), where they received educa-tional materials plus weekly supportive-expressive group therapy, or to the controlcondition (n 5 61), where they received only educational materials for a minimumof 1 year. The treatment, 90 minutes once a week, was designed to build new bondsof social support, encourage expression of emotion, deal with fears of dying anddeath, help restructure life priorities, improve communication with family mem-bers and healthcare professionals, and enhance control of pain and anxiety.

Effects of supportive‐expressive group therapy on survival of patients with metastatic breast cancer

This study was designed to replicate our earlier finding that intensive group therapy extended survival time of women with metastatic breast cancer. Subsequent findings concerning the question of whether such psychosocial support affects survival have been mixed.

Posttraumatic Growth Following the Terrorist Attacks of September 11, 2001: Cognitive, Coping, and Trauma Symptom Predictors in an Internet Convenience Sample

Cognitive, coping, and trauma symptom predictors of posttraumatic growth (PTG; measured with the Posttraumatic Growth Inventory) were examined in a large convenience sample (n =1505) participating in a longitudinal Internet-based study following the terrorist attacks of 9/11/01. Results indicate that initial PTG levels (mean 9 weeks post-attacks) were generally associated with higher trauma symptoms (measured with the PTSD Checklist - Specific), positive changes in worldview (measured with the Changes in Outlook Questionnaire), more denial, and less behavioral disengagement (measured with the Brief COPE). Additionally, PTG had a curvilinear association with level of trauma symptoms, such that those reporting symptoms at intermediate levels reported the highest levels of growth. Levels of PTG declined somewhat over time with the exception of Spiritual Change. As expected, PTG levels at follow-up (mean 6.5 months post-attacks) were primarily predicted by initial PTG levels; however, decreases from baseline ...

Post-transplantation lymphoproliferative disease in heart and heart–lung transplant recipients: 30-year experience at Stanford University

BACKGROUND Post-transplantation lymphoproliferative disease (PTLD) is an important source of morbidity and mortality in transplant recipients, with a reported incidence of 0.8% to 20%. Risk factors are thought to include immunosuppressive agents and viral infection. This study attempts to evaluate the impact of different immunosuppressive regimens, ganciclovir prophylaxis and other potential risk factors in the development of PTLD. METHODS We reviewed the records of 1026 (874 heart, 152 heart-lung) patients who underwent transplantation at Stanford between 1968 and 1997. Of these, 57 heart and 8 heart-lung recipients developed PTLD. During this interval, 4 different immunosuppressive regimens were utilized sequentially. In January 1987, ganciclovir prophylaxis for cytomegalovirus serologic-positive patients was introduced. Other potential risk factors evaluated included age, gender, prior cardiac diagnoses, HLA match, rejection frequency and calcium-channel blockade. RESULTS No correlation of development of PTLD was found with different immunosuppression regimens consisting of azathioprine, prednisone, cyclosporine, OKT3 induction, tacrolimus and mycophenolate mofetil. A trend suggesting an influence of ganciclovir on the prevention of PTLD was not statistically significant (p = 0.12). Recipient age and rejection frequency, as well as high-dose cyclosporine immunosuppression, were significantly (p < 0.02) associated with PTLD development. The prevalence of PTLD at 13.3 years was 15%. CONCLUSIONS The overall incidence of PTLD was 6.3%. It was not altered by sequential modifications in treatment regimens. Younger recipient age and higher rejection frequency were associated with increased PTLD occurrence. The 15% prevalence of PTLD in 58 long-term survivors was unexpectedly high.

Prediction of the development of low birth weight preterm infants by a new neonatal medical index

A new neonatal medical index (NMI) was used to predict the mental and motor development of low birth weight, preterm infants up to 3-years-old. The NMI is a summary score of only a few clinically salient items that are readily available on brief chart review. The sample consisted of 512 of 608 infants randomly assigned to the control group of the eight-site Infant Health and Development Program and on whom the complete set of developmental outcome measures was available. The developmental tests administered were the Bayley Scales at 12 and 24 months and the Stanford-Binet at 3 years. The findings indicated the NMI was predictive of later cognitive and motor development, and in infants born weighing less than 1500 g, the effects of neonatal medical complications continued to adversely influence these childrens development to at least 3 years of age. In the heavier babies the developmental effects of sociodemographic factors predominated by 24 months and beyond.

Psychological distress and pain significantly increase before death in metastatic breast cancer patients.

Objective This study was designed to examine the course of psychological distress and pain from study entry to death in 59 women with metastatic breast cancer participating in a randomized trial of the effects of group psychotherapy on psychosocial outcomes and survival. It was hypothesized that psychological distress would increase significantly before death independent of changes in pain. Method Data were collected as part of a larger study (N = 125). Analyses were based on data from a subset of women who had died and for whom we had data from at least three assessments. Mean levels of mood, trauma symptoms, depression symptoms, well-being, and pain over three time points were examined: at baseline (T1), the second-to-last assessment before death (T2), and the last assessment before death (T3). Results Results indicate that while psychological distress remained relatively constant or declined from T1 to T2, means on all measures significantly changed in the hypothesized direction from T2 to T3. Neither self-reported pain, nor the passage of time, appeared to account for these changes. Additionally, participation in group psychotherapy did not have a significant impact on this change in distress proximal to death. Conclusions Results suggest that specialized end-stage clinical interventions are particularly needed for cancer patients as they approach death. Moreover, intervention studies for patients with deteriorating illnesses may need to take this “spike” in psychological distress and pain proximal to death into account to avoid Type II errors in evaluations of psychological outcomes.

Comparison of lesbian and heterosexual women's response to newly diagnosed breast cancer

In a study comparing lesbian and heterosexual womens response to newly diagnosed breast cancer, we compared data from 29 lesbians with 246 heterosexual women with breast cancer. Our hypotheses were that lesbian breast cancer patients would report higher scores of mood disturbance; suffer fewer problems with body image and sexual activity; show more expressiveness and cohesiveness and less conflict with their partners; would find social support from their partners and friends; and would have a poorer perception of the medical care system than heterosexual women. Our predictions regarding sexual orientation differences were supported for results regarding body image, social support, and medical care. There were no differences in mood, sexual activity or relational issues. Not predicted were differneces in coping, indicating areas of emotional strength and vulnerability among the lesbian sample. Copyright

Effects of supportive-expressive group therapy on pain in women with metastatic breast cancer.

OBJECTIVE To examine whether a group intervention including hypnosis can reduce cancer pain and trait hypnotizability would moderate these effects. DESIGN This randomized clinical trial examined the effects of group therapy with hypnosis (supportive-expressive group therapy) plus education compared to an education-only control condition on pain over 12 months among 124 women with metastatic breast cancer. MAIN OUTCOME MEASURES Pain and suffering, frequency of pain, and degree of constant pain were assessed at baseline and 4-month intervals. Those in the treatment group also reported on their experiences using the hypnosis exercises. RESULTS Intention-to-treat analyses indicated that the intervention resulted in significantly less increase in the intensity of pain and suffering over time, compared to the education-only group, but had no significant effects on the frequency of pain episodes or amount of constant pain, and there was no interaction of the intervention with hypnotizability. Within the intervention group, highly hypnotizable participants, compared to those less hypnotizable, reported greater benefits from hypnosis, employed self-hypnosis more often outside of group, and used it to manage other symptoms in addition to pain. CONCLUSION These results augment the growing literature supporting the use of hypnosis as an adjunctive treatment for medical patients experiencing pain.