Long-term survival after autologous bone marrow transplantation for follicular lymphoma in first remission.

The role of autologous stem cell transplantation (ASCT) in the treatment of follicular lymphoma is still being defined in the era of antibody therapy. Here we report the long-term 12-year clinical outcomes of patients treated with autologous bone marrow transplantation (ABMT) for follicular non-Hodgkin's lymphoma (NHL) in first remission. Between 1988 and 1993, advanced-stage follicular NHL patients in need of initial therapy were enrolled in 2 consecutive prospective treatment trials of either standard-dose CHOP induction (83 patients) or high-dose CHOP plus granulocyte-colony stimulating factor (G-CSF) (20 patients). Patients who achieved an adequate remission with induction therapy underwent conditioning with cyclophosphamide and total body irradiation (TBI) followed by ABMT in first remission using bone marrow (BM) purged in vitro with anti-B cell monoclonal antibodies and rabbit complement (96 patients). At 12-year follow-up, 61% of the patients are alive and 43% remain in continuing complete remission. The only predictors of decreased progression-free survival proved to be histologic BM involvement at time of harvest (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.3-3.9, P<.004) and PCR detectable disease in the BM product after purging (HR 4.18, 95% CI 1.99-8.8, P=.0002). No significant predictors of overall survival were identified. These results at 12-year follow-up suggest that a subset of follicular lymphoma patients can experience prolonged survival with ABMT in first remission.     

The Athletic Prevention Programming and Leadership Education (APPLE) Model: Developing Substance Abuse Prevention Programs

Alcohol and other drug (AOD) abuse affects every sector of society, and student-athletes are no exception. Because many factors affecting athletes do not affect other students, athletic departments commonly approach prevention through AOD education. Different educational approaches are described in this article, particularly the Athletic Prevention Programming and Leadership Education (APPLE) model. Project APPLE is designed to enable an athletic department to systematically analyze its AOD prevention in seven areas: recruitment practices, expectations and attitudes, education and AOD programs, policies, drug testing, discipline, and referral and counseling. Because athletic trainers often are involved in this process, this article should help them to design more effective AOD programs.     

Skin testing in farmers' lung disease

Intradermal skin tests with a culture filtrate antigen of Micropolyspora faeni grown on a synthetic medium were performed on patients with farmers' lung disease (FLD) and well farmers with and without antibodies to a panel of FLD antigens. Seventy-five percent of the FLD patients, 79% of the well farmers with M. faeni antibody, and 5% of well farmers without M. faeni antibody had a 2+ or greater intradermal immediate skin-test reaction. Prausnitz-Küstner (P-K) reactions were positive using serum of M. faeni immediate skin test-positive FLD patients. IgG-rich fractions from a staphylococcal protein A-Sepharose column of such serum contained the sensitizing factor whereas IgG-depleted fractions did not. M. faeni—specific IgE could not be detected in serum by a polystyrene radioimmunoassay. Positive late-onset (6-hr) skin tests occurred only in FLD patients and farmers with precipitating antibody. Biopsy specimens of the 6-hr reactions revealed a generalized dermal and perivascular polymorphonuclear infiltrate with deposits of immunoglobulin and complement about blood vessels. The skin-sensitizing factor noted in FLD patients and well farmers with antibody is not disease specific. This factor appears to be associated with the IgG-rich fraction of serum, and its role in the pathogenesis of FLD is unclear.     

Laboratory and Ambulatory Monitoring of Menopausal Hot Flashes

A large increase in skin conductance activity recorded from the sternum was found during menopausal hot flashes and corresponded well with patient self-reports. The magnitude and time course of this skin conductance change was similar during spontaneous hot flashes recorded in the laboratory, during heat-induced hot flashes, and during those recorded by ambulatory monitoring techniques. This pattern of sternal skin conductance change did not occur in premenopausal women during body heating or ambulatory monitoring. These methods should be useful in research on the etiology and treatment of menopausal hot flashes.     

Hb FM-Fort Ripley: Confirmation of autosormal dominant inheritance and diagnosis by PCR and direct nucleotide sequencing

We describe a normal neonate who presented at four days of age with asymptomatic cyanosis. There was no evidence of cardiac or pulmonary abnormality and an extended family history included 13 other affected family members with asymptomatic cyanosis lasting one to three months. Polymerase chain reaction (PCR) amplification and direct nucleotide sequencing of the proband's Gγ chain gene revealed the mutation at codon 92 (CAC→TAC) previously shown in haemoglobin FM-Fort Ripley (α₂γ₂^{Gγ 92 (F8) His→Tyr}). This is the first family with Hb FM-Fort Ripley reported so far. It demonstrates autosomal dominant inheritance of this condition and incomplete penetrance. © 1994 Wiley-Liss, Inc.     

Evaluation of anhydride oligomers within polymer microsphere blends and their impact on bioadhesion and drug delivery in vitro

The effect of the addition of small molecular weight anhydride oligomers to polymer microspheres was evaluated and increased bioadhesion of the composite was demonstrated. Blends of low molecular weight anhydride oligomers with thermoplastic poly(fumaric-co-sebacic anhydride) [p(FASA)] and polycaprolactone were examined. The effects of anhydride oligomers on polymer microsphere degradation, crystallinity, and surface morphology were also explored. The results demonstrated that fumaric anhydride oligomer remained within polymer microspheres for several hours after exposure to phosphate buffer, formed a homogenous crystalline blend, increased bioadhesion as measured on rat intestine, and enhanced drug delivery in vitro as measured by the everted sac technique.     

Peripheral tolerance to an islet cell-specific hemagglutinin transgene affects both CD4+ and CD8+ T cells.

To study the basis for immunological tolerance of peripheral tissue-specific antigens, a transgenic mouse line was established that expresses the influenza hemagglutinin (HA) on pancreatic islet beta cells (Ins-HA transgenic mice). When followed up to 14 months of age, Ins-HA transgenic mice did not develop spontaneous autoimmune disease. Upon immunization with HA-expressing viruses, high titers of HA-specific circulating antibody were detected; however, T cell responses by both the T helper and T cytolytic compartment were markedly reduced as compared with transgene-negative littermates, and no evidence could be found for islet infiltrates. Adoptive transfer of histocompatible lymphocytes from transgene-negative mice plus virus into irradiated Ins-HA hosts resulted in islet inflammation dominated by CD4+ T cells, indicating that the HA antigen was accessible to activated T cells. These results suggest that T cells can be rendered tolerant of antigens expressed outside the thymus.     

Open-field behavior and the peripheral sympathetic nervous system in the MR/N and MNR/N rat strains

The Maudsley Reactive (MR) and Maudsley Non-Reactive (MNR) strains of rats, respectively selected by P. L. Broadhurst for high and low open-field defecation (OFD), were acquired by the National Institutes of Health in 1963 at the 21st generation of inbreeding and have been inbred as the MR/N and MNR/N strains at that location for more than 40 generations. The present experiment shows that, despite the lack of deliberate selection for more than 40 generations, the strains still differ predictably in OFD. Strain differences in open-field activity, originally found to be inversely associated with those in OFD, have also been preserved. The existence of an association between the peripheral sympathetic system and OFD originally established in the Har derivation of the Maudsley strains was also confirmed in the MR/N and MNR/N strains: MR/N male rats, with the relatively higher levels of OFD, exhibited lower concentrations of norepinephrine (NE) in spleen and descending colon than MNR/N rats. The pattern of biochemical and morphological findings obtained in this study and previous data indicate that the MNR/N and the MNR/Har strains are both derived from the British stocks of this strain carrying the agouti allele (AA). A distinction should be made between these strains and the MNRA/Har strain, which carries the nonagouti allele (aa) and which has been genetically isolated from the Nonreactive strains bearing the agouti allele since early in the selection experiment.Supported by Grant GM 28874 from the National Institute of General Medical Sciences.     

The PROMIS Upper Extremity Computer Adaptive Test Correlates With Previously Validated Metrics in Patients With Carpal Tunnel Syndrome

Background: The Patient-Reported Outcomes Measurement Information System Upper Extremity (PROMIS UE) computer adaptive test was developed to improve precision and reduce question burden. We hypothesized that in patients with carpal tunnel syndrome (CTS): (1) PROMIS UE would correlate with established patient-reported outcome measures (PROs); (2) the time and number of questions required would be lower than current metrics; (3) there would be no floor or ceiling effects; and (4) PROMIS UE would not correlate with disease severity. Methods: Patients undergoing electrodiagnostic evaluation found to have a primary diagnosis of unilateral CTS prospectively completed PROMIS UE, Quick Disabilities of the Arm, Shoulder and Hand (qDASH), and Boston Carpal Tunnel Syndrome Questionnaire (BCTQ). Electrophysiologic and clinical severity was recorded. The relationships among PROs were described with Spearman coefficients. A floor or ceiling effect was confirmed if >15% of patients achieved the lowest or highest possible score, respectively. Results: Fifty-one patients (average, 53.9 years) were enrolled. An excellent correlation was identified between PROMIS UE and qDASH (R = −0.76, P < .001). There was a good correlation between PROMIS UE and BCTQ (R = −0.58, P < 0.001). The PROMIS UE required less time and fewer questions than qDASH and BCTQ (P = .02 and P < .001). There were no floor or ceiling effects. Neither neurophysiologic nor clinical severity correlated with PROMIS UE (R = 0.24, P > .05 and R = −0.18, P > .05). Conclusions: The PROMIS UE has an excellent correlation with qDASH and a good correlation with BCTQ in patients with CTS. Furthermore, PROMIS UE required less time and fewer questions than established PROs. Used as a single PRO, PROMIS UE represents a practical alternative to current metrics in patients with CTS.     

PROMISE: Working with the CF community to understand emerging clinical and research needs for those treated with highly effective CFTR modulator therapy

Highly effective CFTR modulator drug therapy is increasingly available to those with cystic fibrosis. Multiple observational research studies are now being conducted to better understand the impacts of this important therapeutic milestone on long-term outcomes, patient care needs, and future research priorities. PROMISE is a large, multi-disciplinary academic study focused on the broad impacts of starting elexacaftor/tezacaftor/ivacaftor in the US population age 6 years and older. The many areas of investigation and rationale for each are discussed by organ systems, along with recognition of remaining important questions that will not be addressed by this study alone. Knowledge gained through this and multiple complementary studies around the world will help to understand important health outcomes, clinical care priorities, and research needs for a large majority of people treated with these or similarly effective medications targeting the primary cellular impairment in cystic fibrosis.