Calf muscle atrophy and Achilles tendon healing following experimental tendon division and surgery in rats

We used a rat model to study the effects of immobilization of the calf muscle-tendon complex after an experimental Achilles tendon repair. Immobilizations of the complex in either a relaxed or tensioned position were compared by histochemical and morphometric analyses at the site of the tendon injury as well as in the gastrocnemius and soleus muscle bellies. The type of immobilization did not affect the healing of the tendon injury because no reruptures occurred in either of the treatment groups and the average tendon end-to-end distance did not differ between the groups. However, immobilization in a relaxed position led to a significantly more extensive fiber atrophy in the calf muscles. In clinical practice, these results suggest that rehabilitation after Achilles tendon surgery can be early and gradually tension- and load-increasing without a significant increase in the risk of rerupture of the tendon.     

Presence of the IL-1RA Allele 2 (IL1RN*2) is Associated with Enhanced IL-1β Production In Vitro

The genes of the interleukin-1 (IL-1) complex code for three proteins: IL-1α, IL-1β and the IL-1 receptor antagonist (IL-1RA). Each of these genes is polymorphic and there is increasing evidence that certain alleles are associated with increased susceptibility to a given disease of inflammatory nature. In the IL-1β gene there are two base-exchange polymorphisms in positions −511 and +3953, and IL-1RA gene has a penta-allelic polymorphic site in intron 2 containing variable numbers of an 86-bp tandem repeat sequence. As the IL-1β/IL-1RA ratio may be critical in the regulation of inflammation, we examined whether there are allelic associations between these loci (thus suggesting co-ordinate regulation) and whether these have an effect on the in vitro production of IL-1β. We found that the IL-1RA allele 2 (IL1RN*2) is associated with the presence of allele 2 of the IL-1β gene (position −511) and with the absence of allele 2 of the IL-1β gene (position +3953). Mononuclear cells from carriers of allele 2 (position −511) and non-carriers of allele 2 (position +3953) had a slight, but non-significant, elevated capacity to produce IL-1β in vitro . However, IL-1RA allele 2 strongly increased in vitro production of IL-1β, regardless of the presence or absence of these alleles. Taken together, these data suggest that the known allelisms in the IL-1β gene are not major regulators of the in vitro IL-1β production, but the IL-1RA allele 2 (or an unknown allele strongly associated with it) has a decisive role.     

The balance of inhibitory and excitatory cytokines is differently regulated in vivo and in vitro among therapy resistant epilepsy patients

PURPOSE: Excessive neuronal activity and seizures directly stimulate cytokine expression. In this study we investigated cytokine production in circulating blood and peripheral blood mononuclear cells (PBMC) in order to assess the cellular origin of these cytokines in patients with therapy resistant epilepsy. METHODS: We compared the levels of plasma IL-1beta, IL-1Ra and IL-6 in 10 patients with therapy resistant localization-related epilepsy and in healthy volunteers. The spontaneous and exogenously stimulated production of these cytokines was studied in PBMC cultures using EIA. Moreover, cell-specific cytokine production was studied using flow cytometry. RESULTS: Highly pro-inflammatory cytokine profile (high IL-6, low IL-1Ra and low IL-1Ra/IL-1beta ratio) was observed in plasma from patients with epilepsy. Spontaneous and LPS stimulated cytokine release was similar in PBMC cultures of patients and control subjects. When cells were stimulated with OKT3 the cytokine response profiles in patients with epilepsy were almost opposite (anti-inflammatory) to the profile which was observed in circulating blood. Low IL-6 was observed in cell cultures of patients when stimulated with PDBu + A23187. Flow cytometric analysis revealed that the percentages of IL-1beta, IL-1Ra and IL-6 positive monocytes were similar in patients and control subjects. CONCLUSIONS: Patients with therapy resistant epilepsy display a pro-inflammatory profile of plasma cytokines without any evidence of increased production from PBMC. These results suggest that the most likely origin for these cytokines is the brain, where cytokines can exert neuromodulatory functions.     

Effect of lateral release on patellar motion in chondromalacia. An MRI study of 11 knees

Preoperatively and postoperatively, patellar motion in 11 knees with chondromalacia was analyzed by MRI at 0 degrees, 10 degrees, 20 degrees, and 30 degrees of knee flexion. The preoperative patellar position clearly deviated from normal at 0 degrees-10 degrees of knee flexion. The lateral release operation corrected this deviation.     

Invalidity pension after lumbar disc operation

A total of 753 patients (328 women, 425 men) below 65 years of age and without previous pension living in the South-West of Finland, were operated on for the first time for lumbar disc herniation during the period 1975-1979. The frequency of a new invalidity pension was observed during a follow up period of two years. Of the 753 patients there were 100 new invalidity pensioners (13%) during one year and 133 (18%) during two years after the first operation. According to a statistical model for the impact of age and nature of work on invalidity pension the greatest risk of pensioning for women was associated with age, pensioning being more than five times higher in the age group 45-54 years than below 35 years. Moderate and heavy work by women constituted a minor risk factor, increasing the risk by less than two times compared with light work. In men the risk correlated clearly to both age and nature of work. Moderate and heavy work increased the risk nearly three times compared with light work. The frequency of pensions among 45-64 year old men was even 6-8 times higher, than the risk for men below 35 years. A second operation increased the risk on average two to three times. Cauda equina syndrome was not a risk factor for receiving an invalidity pension. The primary diagnosis for an invalidity pension was something other than lumbar disc herniation in 20%. Patients with unsatisfactory results after lumbar disc operations account for about 10% of all the new invalidity pensions due to some form of back disease in Finland.     

CD80 antigen expression as a predictor of ex vivo chemosensitivity in chronic lymphocytic leukemia

We investigated the correlation between expression of 31 surface membrane antigens and chemosensitivity of peripheral blood mononuclear cells from 36 patients with CLL. The sensitivity of CLL cells to nine drugs (2'-chlorodeoxyadenosine, cisplatin, chlorambucil, cyclosporin A, doxorubicin, fludarabine, prednisolone, verapamil and vincristine) and two types of irradiation (gamma and UV-irradiation) was determined from dose-response curves of 4-day cultures ex vivo. The results indicated that the CLL cases responding to purine analogs (2'-chlorodeoxyadenosine and fludarabine) can be identified according to CD80 expression: all resistant cases had low or negative CD80 expression. No other correlations were revealed. CD80 may be a surrogate chemosensitivity marker for purine analogs.     

The IL-1beta genotype carries asthma susceptibility only in men

One proinflammatory cytokine possibly implicated in the pathogenesis of asthma is IL-1beta. We analyzed the polymorphism of the IL-1beta gene (single nucleotide exchange at position -511) in a cohort of 245 patients with asthma (mean age, 58 years; age range, 31-84 years) and 405 controls. There were no differences in the allele frequencies. However, in men the genotype distribution differed significantly between asthmatic and control subjects (P =.03). The number of 1.2 heterozygotes was decreased in the patient group (P =.01). In subgroup analysis, the genotype distributions between cases and controls proved significantly different only in men with lower serum IgE (<100 IU/mL; P =.009). The odds ratio of the 1.2 heterozygote men was 0.37 (95% CI, 0.19-0.71). Thus in the case of men the effect of the IL-1beta locus is clear, whereas in women there is no effect. In men this might make a significant contribution to the total asthma prevalence because of the high number of functional genotypes (ie, 50/50 IL-1beta homozygote/heterozygote ratio).