Gender influence on the outcome of an unisex total knee arthroplasty system.

BACKGROUND: Controversy exists on whether gender-specific anatomic differences in the human knee have to be taken into account by gender-specific design in total knee replacement (TKR). We evaluated total knees that were implanted in both genders. OBJECTIVE: This paper will describe the influence of gender on the outcome after a unisex total knee arthroplasty. METHODS: 52 total knee prostheses (mobile bearing Brehm Precision Knee®, BPK) were implanted in 48 patients (16 male, 32 female, 4 bilateral). Median follow-up was 15 months. HSS score, KSS score, ROM, VAS, and radiologic axis were used as outcome measures. We also obtained preoperative scores of these parameters, creating difference parameters respectively. All surgeries were performed by a single surgeon. RESULTS: No significant difference could be determined between genders for postoperative parameters and difference between preoperative and postoperative parameters between both groups. Women scored higher on HSS score preoperatively and postoperatively with 50.0 and 91.0 points versus 47.0 and 88.0 points in the male group. On KSS score, the female group scored higher preoperatively and postoperatively as well, with 79.0 and 174.0 points versus the male group with 74.0 and 168.0. CONCLUSION: As the results obtained with this unisex prosthesis system were not statistically significant when compared for gender, we conclude the BPK currently addresses gender-specific anatomic differences sufficiently.

[Nickel allergy and painful unicondylar knee arthroplasty]. / Nickelallergie und schmerzhafte monokondyläre Kniegelenksschlittenprothese.

A 56-year-old woman with unicondylar knee arthroplasty (Oxford III, Biomet) complained of persistent, burning pain in her knee. The arthroplasty failure was caused by a nickel allergy. The diagnosis was confirmed by positive patch testing, lymphocyte transformation test and histological analysis of the neosynovia around the implant. The unicondylar knee arthroplasty was explanted and replaced by a titanium-coated knee prosthesis (INNEX CR, Zimmer).

On vanadate phosphate and arsenate framework structures based on the NbO-net.

The recently described framework structure of composition [As(6)V(4+)(12)V(5+)(3) O(51)](-9) is analogous to previously known vanadate phosphate frameworks.

[Pathological findings in tissue surrounding revised metal/metal articulations]. / Pathologische Veränderungen im umgebenden Gewebe von revidierten Metall-Metall-Gleitpaarungen.

INTRODUCTION: The aim of the current study was to elucidate the incidence of allergic reactions to metal/metal articulations in revised total hip arthroplasties. MATERIALS AND METHODS: Between 1 January 1997 and 31 January 2002 a consecutive series of tissue samples from 13 revised total hip arthroplasties with metal/metal articulations were histopathologically examined for signs of delayed type hypersensitivity (DTH). Mean age at the time of revision of the eight women and five men was 58.7 years. The prostheses were revised after a mean follow-up of 45 months. Indications for revision were progressive osteolysis of the proximal femur in 12 cases and instability in one case. All patients were clinically and radiologically evaluated after a mean follow-up of 52 months (min. 22, max. 74) after revision. RESULTS: No signs of infection were found in either histopathological or microbiological examinations. In ten cases, perivascular lymphocytic infiltrates could be found as a sign of DTH. After revision and changing of the articulation all osteolyses healed. CONCLUSION: In 10/13 cases (76.9%) signs of DTH could be detected. The fact that all osteolyses healed after changing the articulation may give a strong hint that there is an immunological contribution to this radiological changes. Metal/metal articulations cannot be recommended as the optimum implant for young patients, as the number of patients with allergic reactions to nickel, chrome or cobalt is increasing continuously.

A complex role for the progesterone receptor in the response to vascular injury.

Clinical studies of hormone replacement therapy to prevent cardiovascular diseases have heightened interest in the cardiovascular effects of progestins. However, the role of the progesterone receptor (PR) in vascular biology has not been studied in vivo. We studied ovariectomized female PR knockout (PRKO) mice and their wild-type (WT) littermates using the mouse carotid artery injury model. Placebo-treated PRKO mice showed significantly greater vascular medial hypertrophy and vascular smooth muscle cell (VSMC) proliferation in response to vascular injury than did WT mice. Progesterone had no significant effect in the PRKO mice, but worsened the response to injury in WT mice. VSMCs cultured from PRKO mouse aortae were markedly hyperproliferative, and their growth was not affected by progesterone. In contrast to the in vivo findings, progesterone inhibited proliferation of WT-derived VSMCs. Furthermore, reintroduction of PR into PRKO-derived VSMCs using adenoviral methods restored progesterone-mediated inhibition of proliferation to these cells. This effect was reversed by the PR antagonist, RU 486. Thus, the effects of PR and progesterone differ markedly between cultured VSMCs and intact blood vessels. These data demonstrate a direct role for the PR in regulating the response to vascular injury and VSMC proliferation.

Growth factor activation of the estrogen receptor in vascular cells occurs via a mitogen-activated protein kinase-independent pathway.

The classical estrogen receptor ERalpha mediates many of the known cardiovascular effects of estrogen and is expressed in male and female vascular cells. Estrogen-independent activation of ERalpha is known to occur in cells from reproductive tissues, but has not been investigated previously in vascular cells. In this study, transient transfection assays in human saphenous vein smooth muscle cells (HSVSMC) and pulmonary vein endothelial cells (PVEC) demonstrated ERalpha-dependent activation of estrogen response element-based, and vascular endothelial growth factor-based reporter plasmids by both estrogen-deficient FBS (ED-FBS) and EGF. In nonvascular cells, ERalpha-mediated gene expression can be activated via mitogen-activated protein (MAP) kinase- induced phosphorylation of serine 118 of ERalpha. However, in vascular cells, we found that pharmacologic inhibition of MAP kinase did not alter EGF-mediated ERalpha activation. In addition, a mutant ER containing an alanine-for-serine substitution at position 118 was activated to the same degree as the wild-type receptor by ED-FBS and EGF in both HSVSMC and PVEC. Furthermore, constitutively active MAP kinase kinase (MAPKK) activated ERalpha in Cos1 cells as expected, but MAPKK inhibited ER activation in PVEC. We conclude that growth factors also stimulate ERalpha-mediated gene expression in vascular cells, but find that this occurs via a MAP kinase-independent pathway distinct from that reported previously in nonvascular cells.

Differential-display polymerase chain reaction identifies nucleophosmin as an estrogen-regulated gene in human vascular smooth muscle cells.

PURPOSE: Atheroprotective effects of estrogen (E2) are well documented and are due in part to direct effects of E2 on vascular cells. We recently demonstrated that human vascular smooth muscle cells (VSMCs) express a functional E2 receptor capable of activatine gene expression. This study was designed to identify E2-regulated genes in human VSMCs. METHODS: VSMC mRNA was screened by differential-display polymerase chain reaction (ddPCR) to identify E2-regulated genes. Quiescent human VSMCs were stimulated with 10% fetal bovine serum in the absence or presence of 10(-8) mol/L E2, and total cellular RNA was harvested. ddPCR was performed in triplicate on each RNA sample and differentially expressed candidate genes were isolated. Differential expression of candidate genes were confirmed by dot blotting and positive bands were identified by sequence analysis. E2-mediated regulation at the protein level was investigated by immunoblotting. RESULTS: ddPCR of RNA harvested from aortic VSMCs identified a 462 bp gene product, EAo8, as a candidate E2- regulated gene. Dot blotting with probes derived from four independent VSMC cultures demonstrated a 5.8 +/- 3.9-fold increase in EAo8 expression in response to E2 treatment (p < 0.05 vs control). Sequence analysis identified EAo8 as nucleophosmin, a nucleolar phosphprotein implicated in the regulation of cell growth and protein synthesis. E2-induced expression of nucleophosmin protein was demonstrated by immunoblotting in both saphenous vein and mammary artery VSMCs. CONCLUSIONS: E2 induces nucleophosmin expression in human VSMCs, and ddPCR is a useful approach for studying estrogen-regulated gene expression in VSMCs.

Effect of vitamin E on human aortic endothelial cell responses to oxidative injury.

Reactive oxygen species produced by the cells present in the arterial wall may cause oxidative damage to cellular components altering endothelial cell (EC) function. Changes in the EC function appear to play a key role in the pathogenesis of atherosclerosis. Human aortic endothelial cells (HAEC) were employed to investigate the protective role of vitamin E upon exposure of endothelial cells to oxidative stress in vitro. HAEC assimilate d-alpha-tocopherol from the media in a dose-dependent manner. Exposure of HAEC to 16.5 mM of the free radical generator 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH) for 16 h decreased cell viability (assessed by trypan blue exclusion) from 90 to 28%. HAEC preincubated with vitamin E at 15, 30, and 60 microM prior to the AAPH exposure resulted in a dose-dependent increase in resistance to oxidative stress and increased cell viability by 37, 66, and 85%, respectively. An increase in prostacyclin (PGI2) production by HAEC in response to AAPH exposure was correlated positively with cell damage and negatively with vitamin E concentration. Interleukin (IL)-1 production also increased in parallel with cell damage induced by AAPH. Vitamin E treatment significantly reduced IL-1 production after AAPH exposure. This modulatory role of vitamin E on HAEC function following exposure to an oxidative stress may reflect its antioxidant protection against lipid peroxidation.

Human vascular smooth muscle cells express an estrogen receptor isoform.

In women, estrogen (E2) exerts a clinically relevant anti-atherogenic effect. The atheroprotective effects of E2 are mediated both by E2-induced changes in systemic factors and by direct effects of E2 on the blood vessel wall. In studies to characterize E2 signaling pathways in vascular smooth muscle cells (VSMC), we recently demonstrated that human VSMC express a functional estrogen receptor [1]. In the present study, we applied a reverse transcription/PCR-based strategy to identify isoforms of the E2 receptor in human VSMC. We now report that in addition to the classical E2 receptor, human VSMC derived from both mammary artery and saphenous vein express an estrogen receptor isoform containing an in-frame deletion of Exon 4 (ER delta 4). RNase protection assays confirm the presence of ER delta 4 message in VSMC and demonstrate it is nearly as abundant as the classical E2 receptor. Transient transfection experiments in VSMC and HeLa cells demonstrate that, in contrast to the classical 67 kDa nuclear-localized E2 receptor, ER delta 4: (a) is a 55 kDa protein that is widely distributed throughout the cell; (b) does not transactivate an E2 response element-driven reporter plasmid in response to E2; and (c) does not modulate transactivation of the ERE-reporter by the classical (wild type) estrogen receptor. Thus, human VSMC express an E2 receptor isoform that does not appear to alter gene transcription. The presence of a novel isoform of the E2 receptor may have important implications for studies of E2-mediated signaling in VSMC.

Both lisinopril and verapamil reduced platelet-derived growth factor-A chain mRNA levels in human saphenous vein endothelial cells stimulated by thrombin.

BACKGROUND: Both angiotensin-converting enzyme inhibitors and calcium channel blockers decrease postinjury intimal thickening in vivo, but their mechanisms of inhibitory action are unclear. Expression of the gene for platelet-derived growth factor (PDGF), a smooth-muscle mitogen, in endothelial cells (ECs) after vessel injury has been postulated to cause intimal thickening. In this study, we tested whether lisinopril, an angiotensin-converting enzyme inhibitor, or verapamil, a calcium channel blocker, would suppress the PDGF gene expression in stimulated human saphenous vein ECs. METHODS: Drugs were added to replicate EC cultures 30 minutes before adding 10 units/ml alpha-thrombin. Changes in PDGF-A chain mRNA levels were measured by Northern blot analysis or reverse transcription-polymerase chain reaction method. PDGF-AA homodimer in conditioned media was measured by ELISA: RESULTS: Lisinopril attenuated the induction by thrombin of PDGF-A chain mRNA levels significantly in human ECs at doses of 10(-6) mol/L and 10(-5) mol/L (p < 0.05) and appeared to decrease PDGF-AA homodimer released in conditioned medium. Verapamil also reduced thrombin induction of PDGF-A chain mRNA levels significantly at a dose of 10(-5) mol/L (p < 0.05) and appeared to reduce PDGF-AA homodimer secretion. CONCLUSIONS: These data suggest that one means by which lisinopril and verapamil both suppress intimal thickening might be inhibition of PDGF-A chain gene expression in ECs regrowing over vessel injury areas that are sites of thrombin generation.

Heparin and dibutyryl cAMP modulate gene expression in stimulated human saphenous vein smooth muscle cells.

Increased expression of basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF) A chain, and tissue plasminogen activator (tPA) by smooth muscle cells (SMC) has been postulated to mediate the progression of intimal hyperplasia. We tested whether heparin would suppress the expression of these genes in stimulated human saphenous vein SMC. Quiescent cultured human saphenous vein SMC were stimulated for 4 h with heat-inactivated fetal bovine serum (10% by vol) in the presence or absence of heparin (1 to 250 micrograms/ml). Heparin (50 micrograms/ml) attenuated the induction by serum of bFGF mRNA, tPA mRNA, and tPA secretion. Nonanticoagulant heparin also attenuated serum induction of bFGF and tPA mRNA levels. To further study the role of second messenger signaling, a more specific mode of SMC stimulation was used with thrombin (3 U/ml) in the presence or absence of dibutyryl cyclic AMP (Bu2-cAMP; 0.5 mM). In contrast to heparin, which had no effect on PDGF expression, Bu2-cAMP decreased the induction by thrombin of PDGF-A chain mRNA levels. In thrombin-stimulated SMC, Bu2-cAMP significantly decreased secretion of PDGF-AA protein. Thrombin, however, caused an increase in bFGF mRNA levels which was potentiated by Bu2-cAMP with associated potentiation by Bu2-cAMP of intracellular bFGF protein levels. The induction of tPA mRNA and tPA secretion by thrombin was sharply blocked by Bu2-cAMP. These results suggest that heparin reduces intimal hyperplasia at least partly via partial inhibition of SMC gene expression.

[Joint-preserving osteotomy in segmental femur head necrosis]. / Gelenkerhaltende Osteotomien bei der segmentalen Hüftkopfnekrose.

Joint-preserving osteotomies for segmental necrosis of the femoral head are clinically important, as necrosis often occurs in relatively young people in whom one is hesitant to perform femoral head replacement. The principle in all joint-preserving osteotomies is to remove the necrotic area from the zone subject to load, thereby guarding against indentation of the joint surface. The most universal and most frequently indicated osteotomy is intertrochanteric valgus flexion osteotomy with ventral capsule resection. The result of the operation depends mainly on the extent of the necrosis. If the angle of the necrosis is under 200 degrees, the hip joint can be preserved with great precision and in a good enough state to allow joint replacement to be postponed for many years.

Hormonal influence on endothelial cell angiotensin-converting enzyme activity.

The influence of various hormones on angiotensin-converting enzyme (ACE) production and release by bovine endothelial cells in culture was studied. Dexamethasone, thyroxine (T4), and triiodothyronine (T3) stimulated ACE activity in cells and their culture supernatants without affecting cell number or protein content. The stimulating effects of dexamethasone and thyroid hormones were additive, suggesting that these hormones may have different sites of action. In addition, their stimulating effects were blocked by cycloheximide, indicating that increased enzymatic activity occurred through new protein synthesis. The exposure of cells to insulin reduced ACE activity of cells and their culture supernatants without influencing cell counts or protein content; insulin also partially inhibited the stimulation of ACE activity by dexamethasone or T3. Our studies suggest that the production of ACE by endothelial cells is under hormonal regulation. Release of ACE activity into culture supernatants parallels changes in cellular ACE activity. The results supplement previous observations made in vitro and in vivo.

Endothelial cell damage after gamma-irradiation in vitro: impaired uptake of alpha-aminoisobutyric acid.

The effects of gamma-irradiation with a cesium-137 source were assessed on endothelial cells isolated from bovine pulmonary arteries and maintained in culture. The radiobiologic parameters that characterize the dose-response survival curve for these cells, expressed as mean +/- SD were found to be n = 1.6 +/- 0.2, Dq = 71 +/- 13 rads, and Do = 161 +/- 35 rads, indicating a relatively low capacity of these cells to accumulate or repair radiation damage. Increasing doses of radiation led to decreasing uptake by endothelial cells of [14C]2-aminoisobutyric acid (AIB), a Na+-dependent and nonmetabolizable amino acid. A dose of 500 rads, which caused marked inhibition of cell survival, resulted in a 45% decrease in AIB uptake at 6 h and a 69% decrease in uptake at 24 h after irradiation. No morphologic abnormality was noted in these cells by light microscopy at 24 h after this dose of radiation. Bovine pulmonary artery fibroblasts, on the other hand, showed no significant impairment in uptake of AIB 24 h after exposure to doses of radiation as high as 5,000 rads. The uptake by endothelial cells of [14C]1-aminocyclopentane-1-carboxylic acid, an amino acid transported by a Na+-independent process, was not influenced by 5,000 rads of radiation. Our studies show that endothelial cells are sensitive to radiation and that impaired Na+-dependent uptake of AIB represents an early event in radiation damage to the endothelial cell.

[Preventive aspects and problems of a rural health project in Chad--the need for health motivation]. / Präventive Aspekte und Probleme eines ländlichen Gesundheitsprojektes im Tschad - Das Bedürfnis nach Gesundheitsanimation.

Some of the main difficulties encountered in health work in developing countries depend on the sociocultural conditions. Health animatiod until now) of rural health care. Its implementation requires the training and recycling of existing health personnel as well as of parts of the population. It includes the concept of "barefoot doctor", which corresponds well to the prevailing priority health needs. One should note potential difficulties, however, for example in regard to the way the barefoot doctor is to be remunerated (the author discusses some possibilities). It isn't easy either, in practice, to mobilize the community through health education and to obtain its participation in prevention and health promotion measures. The crucial element is to win its confidence. The author describes his practical experiences in Chad in this respect. Health animation stimulates the responsabilization and the development of a prospective outlook in people, and can thus make an important contribution to their overall development efforts. It is necessary to fight factors which slow down such an evolution, among which certain habits as well as obstacles of an administrative nature.

Eight-membered cyclosilicate rings in muirite.

The determination of the crystal structure of muirite, Ba(10)(Ca,Mn,Ti)(4)Si(8)O(24)(Cl,OH,O)(12) . 4H(2)O, revealed the presence of discrete cyclic silicate anions, (Si(8)O(24))(16-), formed by the condensation of eight silicate tetrahedra. This first reported occurrence of eight-membered rings is of particular interest, because rings with eight tetrahedra are reported to be energetically less stable than rings with six tetrahedra, which have been found in many minerals.