Identification of radiologic healing phenomena in patients with rheumatoid arthritis.

OBJECTIVE: Conventional radiographic scoring methods in rheumatoid arthritis (RA) are designed to quantify progression and disregard any improvement. Reparative changes observed during longterm followup of RA have rarely been described as healing phenomena. Healing may become increasingly important with the availability of more potent antirheumatic drugs. We investigated whether radiologic healing phenomena can be identified by different observers in a blinded fashion. METHODS: Healing phenomena were defined as (1) reappearance (and sclerosis) of the cortical plate, (2) partial or complete filling in of an erosion, or (3) subchondral bone sclerosis with osteophyte formation (secondary osteoarthritis). Pairs of radiographs of hands, wrists, and forefeet [taken 2 to 8 (mean 4.8) yrs apart] of 34 patients were selected from longterm studies: 24 sets with healing phenomena and 10 with progressive disease without healing. The radiographs were blinded and read in pairs in random order by 3 observers unaware of the patients selected for the study. One observer read the set a second time after 8 weeks, resulting in a total of 4 observations. Thirty-eight joints were rated 0 to 5 depending on the amount of surface destruction. In addition an attempt was made to identify joints with healing phenomena. The data were analyzed with help of descriptive statistics such as means, standard deviations, and frequency tables. RESULTS: Out of 1292 joints scored at the second time point, 74 had healing phenomena. These joints were identified in a mean of 89% (95/89/88/82%, respectively) in the 4 observations performed by the 3 readers. Patients without healing phenomena were correctly identified by all observers. In 54 joints less typical healing phenomena were seen in all observations. Sixty-two joints with healing in addition to the 74 joints were seen in 3 observations, 76 in 2, and 127 in one observation. All observers agreed that 1090 joints had no healing phenomenon. The 24 patients with healing had a slight reduction in the Ratingen score, while the 10 patients without healing showed a moderate progression. In the group with healing an increase and decrease in the score occurred in the same patients at different joints. CONCLUSION: In patients with RA followed for several years healing or reparative changes of erosions can be observed. These phenomena can be identified by different observers with high sensitivity even when the observers are blinded to chronological sequence of the films.

[Susceptibility to infections in diabetes--effects on metabolism]. / Infektanfälligkeit bei Diabetes--Einfliüsse auf den Stoffwechsel.

Diabetic patients suffer from recurrent episodes of infections. The cellular and the humoral elements of the defense system against germ invasion are disturbed by the diabetic metabolism. Neuropathy and vascular damage promote the development of wounds and inhibit their healing. Altered motility of the gastrointestinal and the urinary tract lead to increased penetration of bacteria even there. Rare bacteria, atypical courses and frequent complications of infections result in delayed diagnosis and therapy. Dehydration, electrolyte disturbances, malnutrition, and reduced general conditions even increase susceptibility to an infection. On the other hand, an infection deteriorates the metabolic situation in diabetes, resulting in the need for higher insulin doses, or insulin injections in patients normally on oral medication. Altered every-day-life with modified food intake and reduced physical activity complicate diabetes therapy. Neuropathy, angiopathy, retinopathy, nephropathy and other diabetic complications can be triggered and aggravated during the course of an infection. To disrupt this vitious circle of hyperglycemia enforcing infections, which then raise blood glucose, it is necessary to know about the characteristic features of the interactions of diabetes and infection.

[Comparison of granulocyte function in diabetes mellitus type 1 and type 2]. / Granulozytenfunktion im Vergleich zwischen Diabetes mellitus Typ 1 und Typ 2.

The phagocytosis rate of polymorphonuclear leucocytes was measured by flow-cytometry. Vital bacteria were incubated in whole blood. 111 blood samples were measured, 54 in diabetic patients (14 type 1 and 40 type 2), the rest of 57 samples in healthy controls. Results showed firstly, that a decompensation in glucose metabolism in diabetic patients correlated with a decrease in phagocytosis. The HbA1 level was more closely correlated than the glucose level. The second result was, that despite a similar grade of decompensation in type 1 and type 2 diabetic patients, the phagocytosis was significantly lower in type 1 diabetes. No correlation was found concerning age and sex. These findings show, that the impact on granulocytic function in diabetes is of multifactorial origin, not only a shorter or longer elevation of the serum glucose level can explain it solely.

Beta-2-microglobulin adsorption and release in-vitro: influence of membrane material, osmolality and heparin.

We studied the effects of cuprammonium rayon (CR), polyacrylonitrile (PAN), polysulfone (PS), changes in osmolality, and heparin dosage on beta-2-microglobulin (b2M) handling in an in-vitro model that excluded convective transport and minimized diffusive transport. Both PAN and PS exhibited high adsorption capacity for b2M. Osmolality changes had no effect on b2M adsorption or release. CR membrane adsorption was minimal but increased slightly when higher heparin doses were used. In experiments with CR and high heparin doses (4 U/ml) b2M release occurred during the first 15 minutes of in-vitro dialysis, but this increase was inhibited by removing the leukocytes from the blood, indicating that b2M is released from leukocytes.

Influence of cold and warm acclimation on neuronal responses in the lower brain stem.

Neurons in two lower brain stem areas, the nucleus raphe magnus and the subcoeruleus region, have been shown to be part of the thermoafferent system. It is concluded from microcut experiments in unanaesthetized guinea pigs that inhibition of shivering caused by nucleus raphe magnus stimulation is mediated partly by ascending and partly by descending efferents of the nucleus raphe magnus. Electrical stimulation of the subcoeruleus area caused excitatory metabolic responses. Interruption of the ascending efferents of the subcoeruleus area did not prevent the metabolic activation. It is concluded that the excitatory responses are partly mediated by descending efferents of the subcoeruleus area. The descending pathways project mainly to motoneurone pools and to dorsal horn cells. In cold-acclimated guinea pigs, the average maximum activity of bell-shaped subcoeruleus cold-responsive units was reduced significantly in comparison with cold-responsive neurons in animals acclimated to normal room temperature. Furthermore, peak activity of warm-responsive units in the nucleus raphe magnus was larger in cold-acclimated animals than in animals acclimated to normal room temperature. These neuronal changes may contribute via descending lower loops and via ascending upper loops to long-term slope reduction of metabolic cold defence and shivering threshold displacements.

Polyacrylonitrile complement activation attenuated by simultaneous ultrafiltration and adsorption.

The highly permeable synthetic polyacrylonitrile (PAN) membrane (Filtral; Hospal, Basle) is regarded as biocompatible for its slight complement activation and leucocyte sequestration. The low C3a and C5a concentrations during PAN dialysis may be due to a lack of complement activation potential of this polymer, but also to elimination of activated complement components by the dialyser through adsorption and/or ultrafiltration (mol wt of C3a and C4a 9000 daltons; of C5a 11,000 daltons). Comparing arteriovenous differences throughout the study, higher concentrations of C3a (+23%; n.s.) and C5a (+80%; P less than 0.05) were measured in the efferent blood lines, suggesting a slight complement activation by the alternate pathway. A significantly lower C4a concentration in the efferent blood lines (-30%, P less than 0.05) indicates an elimination within the dialyser. Significantly higher arteriovenous concentration differences at the beginning of dialysis and increasing sieving coefficients suggest elimination by adsorption, mainly in the first 20 min of haemodialysis. The continuous decrease of C3a and C4a plasma concentrations in the afferent blood line suggests transport across the membrane and removal by the dialysate. Accordingly, measurable amounts of these complement components were detected in ultrafiltrate.