The role of biologics in treatment of connective tissue disease-associated interstitial lung disease.

With an increased understanding of the molecular pathways of inflammation and autoimmunity, the development of targeted biological agents has revolutionized the management of connective tissue diseases (CTDs). There has been an explosion in the development of these drugs in the last decade, targeting diseases in diverse fields including: allergic disorders, oncology, neuroinflammatory disorders, inflammatory bowel disease, macular degeneration and CTDs. In this last field, commonly applied biologics fall into two categories: cytokine inhibitors and lymphocyte-targeted therapies. The former group includes the antitumour necrosis factor alpha (TNF-α), anti-interleukin (IL)-6 receptor monoclonal antibodies and IL-1 receptor antagonists, whilst the latter encompasses the anti-CD20, B-cell depleting, monoclonal antibody (mAb), Rituximab and the anti-T-cell activation agent, Abatacept. This review will examine our developing experience in the use of these agents in the treatment of CTD-related interstitial lung diseases, with a particular focus on B-cell depletion.

Fibrin sealant reduces the duration and amount of fluid drainage after axillary dissection: a randomized prospective clinical trial.

BACKGROUND: Patients who have axillary dissections during lumpectomy or modified radical mastectomy for breast carcinoma accumulate serosanguinous fluid, potentially resulting in a seroma. Currently accepted practice includes insertion of one or more drains for fluid evacuation. This multicenter, randomized, controlled, phase II study was undertaken to evaluate whether a virally inactivated, investigational fibrin sealant is safe and effective when used as a sealing agent to reduce the duration and volume of serosanguinous fluid drainage and to determine the dose response of this effect. STUDY DESIGN: Patients undergoing lumpectomy or modified radical mastectomy were randomized to treatment with 4, 8, or 16 mL of fibrin sealant or control (no agent) at the axillary dissections site. Patients undergoing modified radical mastectomy also received an additional 4 or 8 mL of fibrin sealant at the skin flap site. Efficacy was evaluated by the number of days required for wound drainage and the volume of fluid drainage compared with control. Safety was confirmed by clinical course, the absence of viral seroconversion, and no major complications attributable to the sealant. RESULTS: The 4-mL axillary dissection dose of fibrin sealant significantly reduced the duration and quantity of fluid drainage from the axilla following lumpectomy (p < or = 0.05). In the modified radical mastectomy patients, a 16-mL axillary dissection dose combined with an 8-mL skin flap dose was significantly effective in reducing the number of days to drain removal (p < or = 0.05) and fluid drainage (p < or = 0.01). There were no fibrin sealant patient viral seroconversions and no major complications attributable to the sealant. A number of wound infections were noted, although this may represent a center-specific effect. CONCLUSIONS: Application of fibrin sealant following axillary dissection at the time of lumpectomy or modified radical mastectomy can significantly decrease the duration and quantity of serosanguinous drainage. The viral safety of the product was also supported.

Fibrin sealant: clinical use and the development of the University of Virginia Tissue Adhesive Center.

The utilization of fibrin sealants to augment hemostasis, seal tissues, and facilitate targeted delivery of drugs is increasing. In 1985, a hospital-based program was established to provide autologous and allogeneic cryoprecipitate that serves as a fibrin sealant when combined with bovine thrombin. To date, more than 4,000 patients have been treated with this product at our institution, with an efficacy rate greater than 90%. Collaboration among surgical services and the blood bank fostered multispecialty expertise with this product that led, in 1997, to the establishment of the University of Virginia Tissue Adhesive Center. The Tissue Adhesive Center is a multidisciplinary center whose physician director and nursing and administrative support staff facilitate basic research, laboratory investigation, and preclinical and clinical trials with collaborators throughout the university. The Tissue Adhesive Center also provides educational programs and clinical consultation, and tracks and participates in peer review of sealant use. The licensure of a commercially produced, virally inactivated, pooled-plasma fibrin sealant in May 1998 provided an alternative source of adhesive. Utilization of the commercial product surpassed use of the blood bank product in April 1999. At present, use of the commercial product is approximately 3 times that of the blood bank-produced sealant. This report reviews the clinical uses of fibrin sealant, its regulatory history, the production of fibrin sealants, the evolution of a blood bank fibrin sealant program, the development of the Tissue Adhesive Center, and the utilization of commercial and blood bank-produced sealant at our university hospital.

Self-reported symptoms and exercise-induced asthma in the elite athlete.

PURPOSE: The purpose of this study was to compare self-reported symptoms for exercise-induced asthma (EIA) to postexercise challenge pulmonary function test results in elite athletes. METHODS: Elite athletes (N = 158; 83 men and 75 women; age: 22 +/- 4.4 yr) performed pre- and post-exercise spirometry and were grouped according to postexercise pulmonary function decrements (PFT-positive, PFT-borderline, and PFT-normal for EIA). Before the sport/environment specific exercise challenge, subjects completed an EIA symptoms-specific questionnaire. RESULTS: Resting FEV1 values were above predicted values (114--121%) and not different between groups. Twenty-six percent of the study population demonstrated >10% postexercise drop in FEV1 and 29% reported two or more symptoms. However, the proportion of PFT-positive and PFT-normal athletes reporting two or more symptoms was not different (39% vs. 41%). Postrace cough was the most reported symptom, reported significantly more frequently for PFT-positive athletes (P < 0.05). Sensitivity/specificity analysis demonstrated a lack of effectiveness of self-reported symptoms to identify PFT-positive or exclude PFT-normal athletes. Postexercise lower limit reference ranges (MN-2SDs) were determined from normal athletes for FEV1, FEF25--75% and PEF to be -7%, -12.5%, and -18%, respectively. CONCLUSION: Although questionnaires provide reasonable estimates of EIA prevalence among elite cold-weather athletes, the use of self-reported symptoms for EIA diagnosis in this population will likely yield high frequencies of both false positive and false negative results. Diagnosis should include spirometry using an exercise/environment specific challenge in combination with the athlete's history of asthma symptoms.

Exercise-induced asthma screening of elite athletes: field versus laboratory exercise challenge.

PURPOSE: The purpose of this study was to compare a laboratory based exercise challenge (LBC) to a field based exercise challenge (FBC) for pulmonary function test (PFT) exercise-induced asthma (EIA) screening of elite athletes. METHODS: Twenty-three elite cold weather athletes (14 men, 9 women) PFT positive for EIA (FBC screened) served as subjects. Twenty-three gender and sport matched controls (nonasthmatics) were randomly selected to establish PFT reference values for normal elite athletes. Before FBC, athletes completed a medical history questionnaire for EIA symptoms. FBC evaluations consisted of baseline spirometry, actual or simulated competition, and 5, 10, and 15 min postexercise spirometry. PFT positive athletes were evaluated in the laboratory using an exercise challenge simulating race intensity (ambient conditions: 21 degrees C, 60% relative humidity). PFT procedures were identical to FBC. RESULTS: 91% of PFT positive and 48% of PFT normal athletes reported at least one symptom of EIA, with postrace cough most frequent. Baseline spirometry was the same for PFT positives and normal controls. Lower limit reference range (MN - 2 SD) of FEV1 for controls suggests that postexercise decrements of greater than approximately -7% indicate abnormal airway response in this population. Exercise time duration did not effect bronchial reactivity; 78% of FBC PFT positives were PFT normal post-LBC. CONCLUSION: Self-reported symptoms by elite athletes are not reliable in identifying EIA. Reference range criterion for FEV1 decrement in the elite athlete postexercise contrasts current recommended guidelines. Moreover, a large number of false negatives may occur in this population if EIA screening is performed with inadequate exercise and environmental stress.

A guide to treating ironman triathletes at the finish line.

The unique physiologic characteristics of an ironman triathlete present challenges to physicians covering ultraendurance events. Cardiovascular emergencies at the finish line are rare. Occult blood in postrace urine is common but rarely of clinical significance. Medical volunteers must distinguish between signs of dehydration, heatstroke, hyponatremia, and postural hypotension and offer appropriate treatment. Recumbent positioning and oral hydration often suffice to stabilize a conscious collapsed athlete, but serious abnormalities require swift evacuation to a hospital.

The long-term hospital treatment of the young chronic patient: follow-up findings.

A follow-up of sixty young-adult psychiatric patients hospitalized at least six months revealed that, at one to three years post-discharge, 83 percent were living in the community. Nearly two-thirds of the 60 patients were actively involved in aftercare treatment. A method of categorizing outcome based on overall level of functioning revealed that good outcomes occurred even among patients whose prognoses, based on treatment history and diagnosis, might be considered guarded. Findings are discussed in relation to the need for information on the efficacy of long-term psychiatric inpatient treatment and the identification of patients who might benefit from this form of care.

Methyldopa in treatment of neurogenic bladder disorders.

Fifty patients with neurogenic bladder dysfunction were treated with methyldopa (Aldomet). The preliminary results that are presented suggest a beneficial action in patients with upper neuron lesions. The probable mechanism of the drug's action is discussed.