Managing COPD: no more nihilism!

This special issue of Patient Education and Counseling is long overdue. During most of the last two decades asthma, and notably asthma self-management has been in the spotlight, while COPD has had to endure a nihilistic approach. The first sign that interest was shifting to the treatment of COPD came from a few large randomized trials on the use of inhaled corticosteroids (ICS) in COPD. Although these studies demonstrated a moderate effect of ICS in COPD, it has become clear that true improvements in the management of this chronic disease will have to come from behavioral interventions. This special issue of Patient Education and Counseling is dedicated solely to the non-pharmaceutical management of COPD. It addresses many issues related to behavioral therapy, such as smoking cessation, exercise training, nutritional aspects, and self-management programs, including action plans to self-treat exacerbations. With the availability of all the treatment and management options, described in this special issue, a nihilistic attitude toward the patient with COPD is no longer justified.     

HLA-DQ-associated predisposition to and dominant HLA-DR-associated protection against rheumatoid arthritis

We have recently proposed a new hypothesis to explain the association of Human Leukocyte Antigen (HLA) with rheumatoid arthritis (RA) predisposition. In this model, which challenges the Shared Epitope (SE) hypothesis, HLA-DQ predisposes while HLA-DR protects. In the present study, we have compared these two models in an Early Arthritis Clinic started in 1993 in the Department of Rheumatology at the Leiden University Medical Centre. Out of 524 patients who enrolled this programme in the period 1993-1998 and completed the one year follow-up, 155 have been classified as RA. These patients along with 306 consecutive cadaveric renal organ donors have been typed for HLA-DR and -DQ. The distributions of predisposing DR alleles according to SE, and predisposing DQ and protective DR according to our model were analysed. We found that two doses of predisposing DQ alleles strongly predisposed to RA, even in individuals with a single dose of SE while DRB1 alleles carrying the motif DERAA confered a dominant protection in DQ5-positive individuals. We conclude that the present findings are consistent with our previously described model of HLA and RA association. Using this new model, we have been able to characterise two novel groups of individuals on the basis of their HLA typing: one strongly predisposed to RA and one protected. Knowing the mechanism of HLA-related dominant natural protection may help in designing novel treatment modalities for RA.     

Simultaneous perfusion of both coronary arteries and drainage of the coronary sinus in the dog heartin situ

A technique is described for perfusion of the entire coronary arterial system of the dog heart in situ and for drainage of the coronary sinus blood. Both coronary arteries are cannulated without ligation of major ventricular branches and disconnected from the aorta. The cannulas are connected to an extracorporeal system allowing perfusion under controlled pressure, without ill effects to either the heart or the blood. The arterial perfusion system is fed from the femoral arteries of the dog. The coronary sinus is cannulated for draining the blood to a venous reservoir against a controlled pressure. From the reservoir the blood is pumped into a femoral vein. Thus a preparation is obtained in which the interdependency of coronary circulation and performance of the heart has been discontinued. Under careful monitoring of pressures and flows, and of blood temperature, blood gases and plasma electrolytes, the preparation has been kept in excellent condition for up to 7 hrs.     

EXTEROCEPTIVE STIMULATION AS A CONTINGENT FACTOR IN THE INDUCTION AND ELICITATION OF DELAYED TYPE HYPERSENSITIVITY REACTIONS TO 1 CHLORO-, 2-4, DINITROBENZENE IN GUINEA PIGS

This study attempted to determine whether a prior period of “stress” would elicit the sensitization reaction of the skin to topically applied chemical agents. A subthreshold concentration of 1-chloro-, 2-4, dinitrobenzene (DNCB) was applied to the skin of 40 guinea-pigs, 20 of which had been subjected to repetitive electrical shocks throughout the previous 15 minutes. They were examined 24 hours later, and were retested with DNCB at another site after 9 days for signs of delayed sensitization. The stressed animals exhibited a more severe contact-reaction (p <. 01) after the induction test and also after the delayed test.     

Measurement of antibody-mediated binding of human polymorphonuclear leukocytes to HSV-1 infected anchorage fibroblasts

A method for the quantitation of effector cell binding to anchorage fibroblast monolayers infected with HSV-1 is described. Human peripheral blood polymorphonuclear leukocytes (PMN) as effector cells were labeled with chromium-51. Fetal human lung fibroblasts were grown to confluency in microtiter plates, infected with HSV-1 and loaded with anti-HSV antibody. The amount of radiolabeled PMN adhering to the monolayer was determined after appropriate incubation and washings. The effector binding assay was shown to be dependent on specific anti-HSV antibodies, antibody concentration, HSV viral expression, and inoculation time. This assay system is especially useful for the evaluation of effector to target cell conjugate formation when applied to anchorage target cells.     

Keratinocyte-derived growth factors play a role in the formation of hypertrophic scars

In predisposed individuals, wound healing can lead to hypertrophic scar or keloid formation, characterized by an overabundant extracellular matrix. It has recently been shown that hypertrophic scars are accompanied by abnormal keratinocyte differentiation and proliferation, and significantly increased acanthosis, compared with normal scars. This study addressed the question of whether the development of normal and hypertrophic scars is regulated by differences in the growth factor profiles of both the epidermis and the dermis. The presence of interleukin-1alpha (IL-1alpha), IL-1beta, tumour necrosis factor-alpha (TNF-alpha), platelet-derived growth factor (PDGF), transforming growth factor-beta1 (TGF-beta1), and basic fibroblast growth factor (bFGF) was investigated in biopsies taken from breast reduction scars at 3 and 12 months following surgery. The samples were analysed by immunohistological methods and categorized as scars that remained hypertrophic (HH), became normal (HN) or remained normal after 12 months (NN). The epidermal expression of IL-1alpha was significantly increased in NN scars compared with HN and HH scars 3 and 12 months following operation, whereas the dermal expression showed no difference. PDGF was significantly increased in the dermis of normal scars after 3 months and in both the epidermis and the dermis of hypertrophic scars after 12 months. IL-1beta, TNF-alpha, TGF-beta and bFGF showed no differences. It is hypothesized that impaired production of keratinocyte-derived growth factors, such as IL-1alpha, leads to a decrease in the catabolism of the dermal matrix, whereas augmented epidermal PDGF production leads to increased formation of the dermal matrix in hypertrophic scars. These observations support the possibility that the epidermis is involved in preventing the formation of hypertrophic scars.     

The pulmonary CO diffusing capacity according to Bates and according to Filley in patients with unequal ventilation

The pulmonary CO diffusing capacity (d l, co) was determined according to Filley et al., by these authors' method and according to Bates et al. in 24 patients with unequal ventilation without severe diffusion disturbances. Under the influence of the unequal ventilation, the Filley method yielded too high D values, while the values according to Bates were too low. The D values obtained by the authors' method were in between the above two extremes.In patients with unequal ventilation, the d value calculated by one of these methods affords little information as to the presence or absence of a diffusion disturbance, and no information on the extent of this diffusion disturbance. Only if D(F) is much too low is there a possibility of a disturbance in diffusion. A normal D(B) or D(K) indicates the probability of absence of a diffusion disturbance.