RelA is required for IL-1beta stimulation of Matrix Metalloproteinase-1 expression in chondrocytes.

OBJECTIVE: Interleukin-1beta (IL-1beta) stimulates collagenase-1 (Matrix Metalloproteinase-1 (MMP-1)) expression in articular chondrocytes, leading to cleavage of type II collagen and irreversible cartilage degradation. The nuclear factor-kappa B (NF-kappaB) pathway is potently activated in IL-1beta-stimulated cells and has been implicated as an intermediate in MMP-1 gene expression. However, the roles of individual NF-kappaB family members during IL-1beta-induced MMP-1 gene expression have not been defined. RESULTS: To address the relationship between the NF-kappaB pathway and MMP-1 gene activation in chondrocytes, primary cultured human articular chondrocyte cultures (HAC) and SW-1353 cells were stimulated with IL-1beta over a 24-h time course and MMP-1, NF-kappaB1, NF-kappaB2 and RelA gene expression was assayed. IL-1beta-induced MMP-1 expression was comparable in HAC and SW-1353 cells both temporally and quantitatively. MMP-1 gene expression was mirrored by increases in NF-kappaB gene expression, and inhibition of NF-kappaB nuclear translocation with dominant-negative IkappaBalpha reduced IL-1beta-dependent MMP-1 gene expression. IL-1beta activated the NF-kappaB pathway in chondrocytes, both through phosphorylation and transient degradation of IkappaBalpha, as well as through sustained phosphorylation of RelA. Small inhibitory RNAs (siRNA) specific for RelA resulted in significant reduction of MMP-1 mRNA, whereas siRNA for NF-kappaB1 and NF-kappaB2 augmented IL-1beta-induced MMP-1 expression. CONCLUSIONS: Our data demonstrate that IL-1beta activation of the NF-kappaB pathway is required for IL-1beta induction of MMP-1 in chondrocytes and that RelA can work independently of NF-kappaB1 or NF-kappaB2 to activate this gene expression program.

High failure rate of a modern, proximally roughened, cemented stem for total hip arthroplasty.

The role of surface finish on the survivorship of cemented femoral stems continues to be debated. A total of 34 proximally roughened cemented stems were implanted in 33 consecutive patients undergoing total hip arthroplasty by a single surgeon. An alarmingly high failure rate was observed, prompting a retrospective chart review, analysis of radiographs, and evaluation of retrieved stems and pathological specimens. Nineteen patients were available with more than two years follow-up. Of these 19 patients, nine stems had failed (47%) due to severe osteolysis and stem loosening. Failures were significantly more common in the male gender (p<0.005), and young (p=0.05), tall (p<0.002), and heavy patients (p<0.004). All failed revised hips showed severe metallosis, with both gross and microscopic evidence of metallic shedding from the stems. Our findings suggest that this proximally roughened stem is susceptible to early failure. Failure is characterized by stem debonding, subsidence within the cement mantle, shedding of metallic and cement particles due to fretting, and rapidly progressive osteolysis. These findings have been observed with other rough surface finish cemented stems.

Developmental dysplasia of the hip in Marfan syndrome.

Among 235 consecutive patients with Marfan syndrome, four cases of developmental dysplasia of the hip were found, amounting to an incidence of 2%. Harness treatment was not effective in any of the patients because of a narrow stable zone and knee laxity. One patient died of cardiac failure before further treatment could be attempted. Closed reduction and spica cast treatment was successful in all other patients. Stability was achieved within a normal period, and there were no redislocations. Consequently, the dislocated hip in patients with Marfan syndrome should be managed early with this method.

Core decompression for avascular necrosis of the distal femur: long term followup.

Seventy-nine knees (45 patients) with a diagnosis of avascular necrosis of the distal femur treated between 1978 and 1989 were evaluated. All patients had a corticosteroid association (had been treated with >30 mg of prednisone for >2 weeks predating by at least 6 months the onset of avascular necrosis). Thirty-two knees were managed with protected weightbearing and rest. Core decompression was performed at a minimum of 3 months after the onset of symptoms in another 47 knees. The knees treated with protected weightbearing had an average asymptomatic period of only 11 months and all but 6 (18%) proceeded to total knee replacement within 6 years. Core decompression yielded good or excellent results in 73% of the knees at an average followup of 11 years (range, 4-16 years). Of the 13 knees with failed core decompression, 7 were asymptomatic for greater than 5 years. A subset of 26 knees from each group was matched for age, gender, diagnosis, Ficat and Arlet Stage, and length of followup. The matched noncore group had 23% survival as compared with 74% survival in the core group. This long term followup suggests that core decompression may slow the rate of symptomatic progression of avascular necrosis of the knee. In addition, core decompression may extend the symptom free interval in certain patients and may delay the need for more extensive procedures such as total knee arthroplasty.

[Results of reproduction and health research, the Czech Republic, 1993: Part 2]. / Vysledky pruzkumu reprodukce a zdravi, CR 1993: 2. cast.

This article "aims at the following topics: problems of health of pregnant women, sexual behaviour of young women and attitudes towards health." Data are from a 1993 survey on reproduction and health research in the Czech Republic. (SUMMARY IN ENG)

[Results of reproduction and health research, the Czech Republic 1993: Part 1]. / Vysledky pruzkumu reprodukce a zdravi, CR 1993: 1. cast.

This article "deals with two basic spheres: natality (abortion rate) and family planning. Natality was evaluated by current indicators such as specific female birth rate, by age, aggregate fertility, and/or median age at birth of the first child." Women were also asked about contraceptive use, knowledge of contraceptive methods, and reasons for use or nonuse. (SUMMARY IN ENG)

[Research on reproduction and women's health--Czech Republic, 1993]. / Pruzkum reprodukce a zdravi--CR 1993.

PIP: In the first half of 1993, a survey was carried out in the Czech Republic with detailed questions of reproduction related to women's health. This research could be realized only owing to support of the Centers for Disease Control and Prevention (USA). The questionnaire covered a broad spectrum of questions on pregnancy and delivery, knowledge and usage of contraceptives, mother and infant health care, the sexual life and contraceptive use of young women (15-24 years old), women's health status, the knowledge of and attitudes toward problems of parenthood, knowledge of HIV/AIDS, as well as socioeconomic and demographic characteristics. 3-stage random sampling (cluster sample) was applied in order to obtain representative results for even small areas. In a total of 12,747 households selected, there were 4870 women 15-44 years old, of whom 4497 were interviewed. 64% were married, and 3% were living in consensual union. 18% of the women had elementary education and 8% were attending secondary schools. 31% were Roman Catholics and 5% indicated other religions. According to 1992 data, the total fertility rate was a relatively high 1.72 in the country. 69% of married and previously married women were not currently using any type of contraception (75% of couples with 2 or 3 children and 29% of those without children). The use of contraception was more prevalent among educated women. Of all women 18.5% used coitus interruptus, 15.3% used condoms, 11.5% used IUDs, 7.7.% used oral contraceptives, and 1.9% were sterilized. Among those who had 4 or more children, 27% were sterilized. Among girls 17 years of age more than half had had sexual experience, while among 18-year-old girls 87% did. Over 90% used coitus interruptus or the condom during the first intercourse. Only 8 women (less than 1%) out of 1374 studied who gave birth after January 1, 1988, stated that during their pregnancy they did not obtain prenatal care. Rates of smoking during pregnancy were 20-23% in all and up to 32% of single women. There was fairly good knowledge of HIV/AIDS, particularly in Prague.^ieng