Modelling debonded stem-cement interface for hip implants: effect of residual stresses.

OBJECTIVE: To assess the effect of the residual stresses due to cement curing on the load transfer of cemented hip implants. DESIGN: The load transfer at the stem-cement interface of an idealized hip stem surrounded by cortical bone was investigated using a three-dimensional finite element analysis. A debonded stem-cement interface was considered to simulate a highly polished stem in contact with cement; Coulomb friction at the stem-cement interface was considered. BACKGROUND: Numerical analyses on the load transfer of cemented hip implants do not include residual stresses due to cement curing at the stem-cement interface. METHODS: The magnitude of the residual stresses was determined experimentally. In the finite element model, non-linear contact elements modelled the debonded stem-cement interface. In particular, the compressive radial residual stresses that are generated at the interface, due to the cement expansion during curing, were treated similar to a press-fit problem. RESULTS: The cement stress distributions were affected by the magnitude of the residual stresses. Failing to include residual stresses underestimated the cement stresses at the interface, mainly affecting the radial and hoop stresses. The load was transferred from the stem to the cement more uniformly along the interface once residual stresses were included. CONCLUSIONS: Because there is no chemical bond at the interface between the stem and cement, the interface resistance depends on friction thus radial residual compressive stresses developed by the cement curing play a direct role. RELEVANCE: Implant loosening of cemented hip implants is one of the major causes of late failure of the arthroplasty. The load is transferred from the stem to the bone primarily across the interfaces, consequently modelling accurately the interface is essential in predicting the load transfer.     

Molecular cloning of agonistic and antagonistic monoclonal antibodies against human 4-1BB.

Previously, we prepared two different monoclonal antibodies (mAbs) against human 4-1BB (CD137): an agonistic mAb BBK-1 and an antagonistic mAb BBK-2. In this paper, we describe the molecular cloning of these two mAbs and present comparisons of their amino acid sequences. cDNAs encoding the heavy (H) and light (L) chains of the two mAbs were cloned by screening of cDNA libraries constructed from hybridomas secreting these mAbs. Comparisons of amino acid sequences of the two mAbs showed that, while the constant regions of the H and L chains were identical between the two mAbs, the variable region showed 45% identity in H chains and 48% identity in L chains. This suggests that these two mAbs recognize different epitopes of 4-1BB and may have different effects on the activity of 4-1BB.     

Prevention of Bone Loss by Clodronate in Early Postmenopausal Women with Vertebral Osteopenia: A Dose-Finding Study

This double-masked, placebo-controlled study was undertaken to determine the efficacy and safety of oral clodronate in the prevention of bone loss in early postmenopausal women with vertebral osteopenia. Altogether 610 women with a mean age of 53 years were recruited for the study. They were 1–5 years postmenopausal and their lumbar spine bone mineral density (BMD) was at least 1 standard deviation below the mean of premenopausal women (T-score ≤−1). The subjects were randomized into five study groups to receive either placebo, clodronate 65 mg, 400 mg or 800 mg daily, or intermittent clodronate in 3 month cycles with 400 mg daily for 15 days followed with no treatment for 75 days for 3 years. One hundred and eighty-seven of 509 women who completed the primary study continued in the extension study of 2 years in which previous placebo users were switched to clodronate 800 mg daily, while previous users of 400 mg or 800 mg of clodronate used either placebo or 800 mg of clodronate daily. In the primary study clodronate was administered in the evening, and in the extension 1 h before breakfast on an empty stomach. In the primary study mean changes in lumbar spine BMD were −3.4% in the placebo group and +0.4% in 800 mg clodronate group [difference between groups at 3 years 3.8% (95% CI 2.7% to 4.9%, p<0.0001)], and in the trochanter area BMD −1.1% in the placebo group, and + 0.4% in the 800 mg clodronate group [difference between groups at 3 years 1.5% (95% CI 0.05% to 2.9%)]. During the extension study mean changes in lumbar spine BMD were +1.5% in the clodronate group and −0.2 % in the placebo group [difference between groups 1.7% (CI 0.4% to 3.0%, p = 0.010)] and in trochanter BMD were +2.5% in the clodronate group and no change in the placebo group [difference between groups 2.1% (CI 0.3% to 3.9%, p = 0.007)]. No statistically significant differences between the placebo and 800 mg clodronate groups were found in the femoral neck BMD. In the primary study the urinary excretion of type I collagen aminoterminal telopeptide (NTX) decreased by 44% (p<0.0001 compared with placebo) and that of deoxypyridinoline by 18% (p<0.0001) in the clodronate 800 mg group. In the extension study urinary NTX decreased by 51% (p<0.0001) in those who were switched to 800 mg of clodronate and increased by 67% (p<0.0001) in those who stopped using that dose. There was no difference in the frequency of gastrointestinal complaints between clodronate- and placebo-treated patients in the primary study, but they were more common among women who received clodronate in the extension phase. Clodronate in daily doses of 400–800 mg caused a slight elevation of aminotransferase levels, usually within the reference range. In bone biopsies no defect in mineralization was found. In conclusion, clodronate in a daily dose of 800 mg prevents early postmenopausal bone loss at the sites of the skeleton in which cancellous bone predominates. It effectively reduces bone resorption and bone turnover rate. Antifracture efficacy of clodronate remains to be established by prospective, placebo-controlled trials. Received: 4 March 2002 / Accepted: 9 July 2002     

Long-term neurotoxicity of chlorpyrifos: spatial learning impairment on repeated acquisition in a water maze.

Organophosphate compounds are cholinesterase inhibitors widely used in agriculture, industry, household products, and even as chemical weapons. Their major mechanism of acute toxic action is the inhibition of acetylcholinesterase, which is responsible for the degradation of the neurotransmitter acetylcholine. An organophosphorus ester-induced chronic neurotoxicity (OPICN) syndrome has been proposed. The OPICN syndrome could result from both long-term exposure to subclinical doses of OPs and after acute poisoning. Development of animal models for the cognitive decline are required and could later help to elucidate the mechanisms involved in this long-term effect on the central nervous system. Previously, we have found performance decrements in a four-trial repeated acquisition spatial task in a water maze. The present study includes two experiments to extend the long-term behavioral effects observed. Rats were injected either once or twice with chlorpyrifos (CPF) and then tested months after in a two-trial repeated acquisition task in a water maze. Our results confirm and extend the long-term behavioral effects of subcutaneous administration of CPF. The two treatments used produced performance decrements that suggest functional central nervous system alterations.     

Toxoplasma encephalitis of immunocompetent and nude mice: immunohistochemical characterisation of Toxoplasma antigen, infiltrates and major histocompatibility complex gene products

The experimental infection of immunocompetent and immunodeficient athymic mice with an avirulent encephalitogenic Toxoplasma strain (DX strain) was employed to study the ensuing encephalitic process by use of histological and immunocytochemical methods. In the acute phase of the infection Toxoplasma cysts and tachyzoites were accompanied by an infiltrate composed of macrophages, CD4+ and CD8+ T cells. In the chronic stage a granulomatous encephalitis developed. In contrast to immunocompetent NMRI mice, athymic nude NMRI mice died 3 weeks post-infection because of a generalized toxoplasmosis with predominant involvement of the brain. A salient feature of murine Toxoplasma encephalitis was up-regulation of class I and II major histocompatibility complex (MHC) gene products. Class I antigen was widely expressed on microglial cells and astrocytes. Class II antigen was only expressed on microglial cells despite a considerable astrogliosis. Our results indicate a differential expression of MHC-determined antigens on brain cells in acute and chronic murine Toxoplasma encephalitis.     

Surgical treatment of gastric cancer: retrospective survey of 1,704 operated cases with special reference to total gastrectomy as the operation of choice.

Total gastrectomy is discussed as the operation of choice among different surgical approaches for gastric carcinoma. We prefer the performance of an elective total gastrectomy with systematic lymphadenectomy (compartments I and II) and obligatory splenectomy. A retrospective study of 1,704 consecutive cases of gastric carcinomas showed a better outcome following total gastrectomy in relationship to distal subtotal gastrectomy, but these results cannot be used as evidence because of the lack of a prospective study. Nevertheless, a precise analysis of our cases in regard to tumor site and tumor type could show a frequency of only 6% to maximally 30%, in which elective total gastrectomy may represent a procedure too extensive to justify for an oncological course.     

Comparative evaluation of acute toxicity and antitumor activity of IF-XXV preparation and holoxan

The alkylating agent ifosfamide synthesized according to own method at the Institute of Pharmaceutical Industry, Warsaw, was compared in biological evaluations with Holoxan (Asta-Werke's ifosfamide). No significant differences between tested compounds were found in respect of acute toxicity and antitumor activity in experimental systems in mice.