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PubMed2004

Use of the alkaline in vivo Comet assay for mechanistic genotoxicity investigations.

The alkaline Comet assay was used to investigate the in vivo genotoxicity of 17 compounds. Altogether 21 studies were conducted with these compounds. The investigations were triggered for various reasons. The main reason for performing the studies was to evaluate the in vivo relevance of in vitro genotoxicity findings with 10 compounds. Eight of these compounds showed no effects in the in vivo Comet assay while two compounds induced altered DNA migration patterns in specific organs. The remaining seven compounds were tested to follow up on neoplastic/preneoplastic or chronic toxicity changes as detected in specific target organs identified in rodent studies, to investigate the possibility of site-of-contact genotoxicity and to test the liver as a target organ for a suspected reactive metabolite. For the studies, various organs of rodents were analyzed, depending on the suspected properties of the compounds, including liver, jejunum, leukocytes, stomach mucosa, duodenum, lung and kidney. All tissues were amenable to investigation by gel electrophoresis after simple disaggregation of organs by means of mincing or, in the case of epithelial cells from the gastrointestinal tract, scraping off cells from the epithelium. In conclusion, the Comet assay was found to be a reliable and robust test to investigate in vivo genotoxicity in a variety of rodent organs. Therefore, it is concluded that in vivo Comet assay data are useful for elucidating positive in vitro genotoxicity findings and to evaluate genotoxicity in target organs of toxicity.

Animals↗
PubMed1990

The basis of high resolution separation of small DNAs by asymmetric-voltage field inversion electrophoresis and its application to DNA sequencing gels.

We have previously shown that asymmetric-voltage field inversion electrophoresis produces more uniform separation for fragments between 1 and 50 kilobases (kb) than other modes of pulsed field gel electrophoresis. We now report on the basis of this phenomenon. As in conventional electrophoresis, the pulsed field mobility of DNAs between 1 and 50 kb varies with voltage in a size dependent manner. The complex migration pattern obtained with asymmetric-voltage field inversion electrophoresis reflects the difference between the mobilities of each sized fragment under the conditions used for the forward and reverse fields. We have applied this technique to DNA sequencing gels and find improvement in resolution for single-stranded fragments in polyacrylamide gels.

Base Sequence↗
PubMedDate not supplied

A comparison of genetic variability in strains of Japanese quail selected for heavy body weight.

Electrophoretic analyses of body tissues from three strains of Japanese quail from the Quail Genetic Stock Centre at the University of British Columbia, two selected for heavy body weight and one randombred, were carried out to determine whether genetic variations in selected strains were different from randombred strains. In addition, the data were also compared with those obtained from domestic and wild populations in Japan. The proportion of polymorphic loci was higher in the heavy strains than in the randombred strain. The selected strains also differed from the randombred strain in the allelic frequencies of liver esterase and phosphogluconate dehydrogenase. While the randombred strain was genetically similar to the domestic strains in Japan, the two selected strains were different from each other and from the domestic strains in Japan. This indicates that (1) polymorphic loci have adaptive importance, and (2) heavy body weight can be achieved by separate genetic mechanisms. A previously unreported allele that affects the migration pattern of muscle adenylate kinase was also discovered in one of the selected strains.

Animals↗
PubMed1994

Effect of elevated temperatures on carbon dioxide exchange in Picea rubens.

We examined some of the physiological reasons that may underlie past and expected future migrations of red spruce (Picea rubens Sarg.) by evaluating the effects of high temperatures on photosynthesis and respiration of trees growing on Whiteface Mountain, NY. At temperatures of 35-40 degrees C, the trees exhibited a zero or negative carbon balance. Higher temperatures resulted in cellular disorganization and death. Temperatures around 30 degrees C resulted in reduced CO(2) uptake, a condition that could decrease future reproductive output and competitive stature. We conclude that thermal intolerance explains, at least in part, the absence of red spruce at low elevations and latitudes where temperatures of >/= 30 degrees C occur. We suggest that the thermosensitivity of this species is important with respect to global climate trends and migration patterns.

Journal Article↗
PubMed1995

Association of p53 gene and protein alterations with metastases in colorectal cancer.

Using monoclonal antibody PAb 1801, p53 protein was detected in the neoplastic cells of 39 (46.9%) of 83 colorectal carcinomas studied. Patients with p53+ tumors showed a higher incidence of lymph node and liver metastases (p = 0.035); in patients whose tumors were located in the rectosigmoid, p53 expression also correlated with a more advanced stage according to Dukes' classification (p = 0.015) as well as nodal (p = 0.006) and liver (p = 0.019) metastases. Following amplification of exons 5 to 8 of the p53 gene by means of the polymerase chain reaction technique, single-strand conformation polymorphism analysis disclosed an anomalous migration pattern in 23 of the 39 p53+ tumors and in four of the 35 p53- tumors analyzed. Sequence analysis showed G:C-->A:T transitions in 63.6%, G:C-->T:A and G:C-->C:G transversions in 18.2%, deletions and insertions in 13.6%, and A:T-->G:C transitions in 4.6% of the cases. Loss of heterozygosity was studied in the DNA of 79 patients; allelic loss was found in 29 (49.1%) of the 59 informative patients. Loss of heterozygosity was correlated with p53 overexpression (p = 0.0002) as well as with the presence of mutations as detected by single strand conformation polymorphism analysis (p = 0.0024).

Adenocarcinoma↗
PubMed1994

Analysis of the essential sequences of the factor VIII gene in twelve haemophilia A patients by single-stranded conformation polymorphism.

We report the analysis by single-stranded conformation polymorphism of the essential sequences of the factor VIII(FVIII) gene (total length about 14 kb) including the entire coding sequence, flanking intronic sequences and the putative regulatory sequences 5' to the gene, in twelve unselected haemophilia A patients of Portuguese origin. Direct sequencing of the fragments with an altered migration pattern led to the identification of the disease-producing mutations in five patients. Three of these mutations, namely a 1 bp insertion in a motif of eight consecutive A residues at codon 1439 (FVIIIPorto3); a C to T transition at codon 1966 (Arg-->Stop), found in an inhibitor-positive patient (FVIIIMontijo); and a G to A transition at codon 479 (Gly-->Arg; FVIIIPorto1), have been reported in other ethnic groups. The two novel mutations are the substitution of AG by GG at the 3' end of intron 4 (FVIIILisboa1) destroying the invariant splice acceptor sequence, and a G to A transition at codon 1948 resulting in an aspartic acid substitution for glycine (FVIIIPorto2).

Base Sequence↗
PubMed2000

Rat dorsal root ganglia express distinctive forms of the alpha2 calcium channel subunit.

Calcium channel alpha2 delta subunit is a glycosylated structural subunit consistent of the alpha2 subunit and the delta peptide. Previous studies have indicated distinctive alpha2 subunit expression in rat spinal cord and dorsal root ganglia (DRG). This study examined whether differential glycosylation underlies the molecular basis of distinct alpha2 delta subunits. The migration patterns of deglycosylated alpha2 subunits from rat spinal cord, DRG, brain and skeletal muscle were compared in Western blots. The data reported indicate that there are two forms of the alpha2 subunit in DRG that are different from the alpha2 subunit in other tissues examined, at least at the glycosylation level. Thus, post-translational modification may be important in tissue specific and functional expression of the alpha2 delta subunit.

Animals↗
PubMed2004

Integrating the social and behavioral sciences in an undergraduate medical curriculum: the UCSF essential core.

Dramatic global-migration patterns over recent decades have forever changed the racial, ethnic, social, and cultural makeup of the people of the United States. Simultaneously, the patterns of disease and risk factor distribution within the U.S. population are changing in ways that accentuate the role of lifestyle, behavior, and social and economic differences in the onset and outcomes of disease. Medical school curricula must prepare students to address these demographic realities. The University of California, San Francisco's (UCSF's) redesigned curriculum, launched in September 2001, integrates social, behavioral, and biomedical science education in an early and sustained way. The traditional undergraduate medical structure of two years of basic science plus two years of clinical rotations was replaced with a model divided into three stages spanning four years: the Essential Core, the Clinical Core, and Advanced Studies. The authors summarize the role of the social and behavioral sciences in the UCSF Essential Core-the first 16 months of instruction divided into integrated blocks, each centered on clinical cases. Basic thematic areas (e.g., behavior change, health disparities), content illustrations (e.g., Introduction to the Biopsychosocial Model, The Culture of Medicine), and process considerations (e.g., integration, content order, evaluations) are presented. Special challenges and limitations are also discussed.

Behavioral Sciences↗
PubMed1991

In vivo proliferation of adoptively transferred tumor-infiltrating lymphocytes in mice.

The adoptive transfer of tumor-infiltrating lymphocytes (TILs) in conjunction with interleukin-2 (IL-2) administration can mediate a reduction in established pulmonary and hepatic metastases of a variety of murine tumors as well as in patients with metastatic melanoma. To characterize further the fate of adoptively transferred TILs, the uptake of the thymidine analog 5-[125I]iodo-2-deoxyuridine ([125I]UdR) into the DNA of dividing cells was used to study the in vivo proliferation and migration patterns of transferred TILs in C57BL/6N mice. Animals received 500 rad of total body irradiation prior to cell transfer to separate incorporation of radiolabel into endogenous lymphoid cells from that into transferred TILs. Mice were subsequently treated with i.v. injections of TILs or no cells followed by i.p. injections of Hanks' balanced salt solution or IL-2. At various time points, mice received [125I]UdR, and 20 h later tissues were removed and counted on a gamma analyzer. A proliferation index (PI) was calculated by dividing the mean cpm of organs of experimentally treated mice by the mean cpm of organs of control mice. Animals receiving TILs alone demonstrated small increases in [125I]UdR in the lungs, liver, and spleen of saline-treated controls (PI = 1.4, 1.6, and 1.7, respectively, on day 4), while animals treated with 50,000 U of IL-2 alone showed greater increases in the lungs, liver, kidneys, and spleen (PI = 3.9, 6.1, 3.3, and 15.8). Mice receiving TILs plus IL-2 demonstrated the highest levels of radiolabel incorporation in the same organs (PI = 10.5, 19.4, 10.2, and 22.4). Over a period of 10 days, TIL plus IL-2 treated animals continued to incorporate significantly greater amounts of [125I]UdR for as long as high-dose IL-2 was administered. Animals treated with TILs demonstrated increased incorporation of radiolabel with increasing doses of IL-2. Injection of irradiated TILs did not result in an increased uptake of [125I]UdR into these tissues, thus confirming that TIL proliferation is responsible for the radiolabel uptake in animals receiving TILs alone or TILs plus IL-2. Additionally, fluorescein-labeled anti-Thy-1.1 antibody identified proliferating TILs derived from congenic B6.PL Thy 1a/CY (Thy-1.1) animals in the lungs, spleen, and liver of recipient C57BL/6N (Thy 1.2) mice. In summary, we have demonstrated that adoptively transferred TILs distribute widely after i.v. injection and can proliferate in various tissues especially under the influence of exogenous IL-2.

Animals↗
PubMed1997

Human cytotoxic CD8+ T-lymphocyte clones engraft in severe combined immunodeficient (SCID) mice but show diminished function.

Mice with severe combined immunodeficiency (SCID) provide an in vivo model for studying interactions between human tumor cells and effector cells of the immune system. We studied the behavior of human alloreactive cytotoxic T lymphocytes (CTLs) in SCID mice, including the migration pattern of CD8+ or CD4+ CTL clones to various murine tissues, their engraftment in the absence or presence of recombinant human interleukin 2 (rhIL-2) compared with the engraftment of lymphokine activated killer (LAK) cells, and the in vitro as well as the in vivo function of the engrafted CTL clones. The polymerase chain technique using T-cell-receptor-gamma specific primers revealed the presence of human CD8+ CTL clones in the blood, lungs, and liver of mice receiving rhIL-2 for 14 days, for at least 18 days after intravenous inoculation. Human T cells were transiently detected in the bone marrow, lymph nodes, thymus, and spleen. Although the three CD8+ CTL clones and two CTL lines tested required rhIL-2 for their engraftment, the four LAK cell populations also engrafted in the absence of rhIL-2. In contrast to CD8+ T cells, only low frequencies (<1%) of CD4+ cells could be detected in the blood of the SCID mouse. Engrafted human T cells recovered from the murine blood showed absent or diminished cytotoxicity in vitro against human target cells in five or six experiments, respectively. In addition, when the antitumor activity of engrafted CD8+ clones was investigated in vivo using a xenotransplantation model of human B-cell lymphoma in SCID mice, no significant prolongation of the mean survival time of six treated animals was observed compared with animals treated with rhIL-2 alone. Our results illustrate that although in vitro primed and cultured human CD8+ T cells engraft in SCID mice, their in vitro and in vivo function is impaired.

Animals↗
PubMed2004

Different CFTR mutational spectrum in alcoholic and idiopathic chronic pancreatitis?

OBJECTIVE: Cystic fibrosis transmembrane conductance regulator (CFTR) mutations are responsible for cystic fibrosis (CF) and have been postulated as a predisposing risk factor to chronic pancreatitis (CP), but controversial results demand additional support. We have therefore investigated the role of the CFTR gene in a cohort of 68 CP patients. METHODS: We have performed the CFTR gene analysis using 2 screening techniques. Fragments showing abnormal migration patterns were characterized by sequencing. Patients were classified in alcoholic (ACP) (n = 37) and idiopathic (ICP) (n = 31) chronic pancreatitis. Clinical features of CP and CF were evaluated. RESULTS: Sixteen mutations/variants were identified in 27 patients (40%), most of them (35%) presenting a single CFTR mutant gene. The 1716G/A variant showed the highest frequency accounting for 22% in ICP and 5% in ACP, in contrast with other more common mutations such as F508del found in 8% of ACP and the 5T variant identified in 7% of patients. Acute pancreatitis, abdominal pain, tobacco, pancreatic calcifications, and pancreatic pseudocysts showed significant higher values in ACP than ICP patients. No significant differences were found between patients with and without CFTR mutations. CONCLUSIONS: Apart from reinforcing previous findings our data highlight the increased susceptibility of CFTR heterozygous to developing CP. Heterozygosity, combined with other factors, places these individuals at greater risk.

Adult↗
PubMed2002

Prevalence of HIV among truck drivers visiting sex workers in KwaZulu-Natal, South Africa.

BACKGROUND: Although the role of mobile populations in the spread of HIV has been documented in several countries, there are few data on HIV among truck drivers in South Africa and the sex workers with whom they interact. GOAL: To determine HIV prevalence and risk behavior in a sample of truck drivers visiting commercial sex workers at truck stops. STUDY DESIGN: Two sex workers from each of five truck stops were trained to obtain informed consent, administer questionnaires to obtain data on demographic and migration patterns, and collect saliva samples for HIV testing from their clients. Data on HIV prevalence and demographic characteristics of sex workers operating at the truck stops were obtained from an ongoing vaginal microbicide trial. RESULTS: The mean age of the truck drivers (all men) was 37 years (range, 18-71 years), and that of the sex workers (all females) was 25 years (range, 15-49 years). Sixty-six percent of the men reported having a sexually transmitted infection in the previous six months, and 37% always stopped for sex along the route. Twenty-nine percent reported never using condoms with sex workers, whereas 13% had used condoms with their wives. All men traveled to more than one province in South Africa, and 65% traveled to neighboring countries. Anal sex was practiced by 42% of the men. The overall HIV prevalence (in the two groups combined) was 56%. CONCLUSION: Truck drivers may have facilitated the spread of HIV infection throughout southern Africa.

Adolescent↗
PubMed1983

Recirculation of indium-111-labeled lymphocytes in normal and allografted rats.

The kinetics of lymphocyte recirculation in normal and allografted rats with acute cardiac rejection was studied with indium-111 (In-111) labeled splenic lymphocytes in two groups of rats. Group 1 consisted of subgroups of normal Lewis rats infused with In-111 labeled unsensitized syngeneic cells (group 1a); ACI-sensitized syngeneic cells (group 1b); and ACI spleen cells (group 1c). Four rats from each subgroup were killed at 3, 6, 18, and 24 hr after cell infusion for blood, spleen, mesenteric lymph node (MLN), thymus, bone marrow (BM), liver, kidney, muscle, and heart scintillation counts. Group 2 consisted of Lewis recipients of ACI cardiac allografts infused with normal or with ACI-sensitized syngeneic splenic cells. Four rats from each subgroup were killed daily until rejection (day 7) for isotope counts of various organs. In ungrafted rats (group I), splenic accumulation of unsensitized syngeneic cells fell from 50% of the total injected dose/g tissue at 3 hr to 28% at 24 hr, whereas it rose from 12% at 3 hr to 39% at 24 hr in MLN. In contrast, the sensitized syngeneic and allogeneic cells homed preferentially to the spleen with insignificant accumulation in the MLN throughout the experiment. The BM and liver showed moderate accumulation while the thymus and nonlymphoid organs had low concentrations of labeled cells at all times. Splenic accumulation of unsensitized syngeneic cells in allografted rats (group II) showed a steep rise from day 1, reaching a peak at day 3, followed by a plateau--but sensitized cells demonstrated a peak on day 4 followed by a sharp decline until rejection. Accumulation of unsensitized cells in the MLN was significantly higher (P less than 0.001) than that of sensitized cells throughout the study. There was a significant fall (P less than 0.001) in radioactivity of BM, thymus, liver, and nonlymphoid organs from days 1-7, and the cardiac allograft demonstrated a reciprocal sharp rise in radioactivity. There was a significant early accumulation (P less than 0.001) of sensitized cells compared with unsensitized cells in the cardiac allograft on day 1. This study shows that In-111 labeled donor cells bearing surface antigen different from that of the recipient were sequestered from the circulating pool and immobilized in the spleen, but labeled donor cells with similar surface antigen to that of the recipient were recruited into the lymph node lymphocyte recirculating pool. It further demonstrates the difference in migration patterns of normal and sensitized syngeneic cells during acute allograft rejection.

Animals↗
PubMed1985

Reactivity of in-vitro-expanded alloimmune cytotoxic T lymphocytes and Qa-1-specific cytotoxic T lymphocytes against AKR leukemia in vivo.

The ability of alloimmune spleen cells expanded in mixed leukocyte culture (MLC) and cloned cytotoxic T lymphocytes (CTL) to kill H-2-compatible leukemia in vivo was evaluated. In comparison with fresh alloimmune spleen cells, MLC-expanded cells had a significantly higher frequency of CTL reactive against leukemia targets in vitro. However, the reactivity of MLC-expanded cells against first-passage spontaneous AKR (H-2k) leukemia in vivo was significantly less than when an equivalent number of fresh alloimmune spleen cells was injected. Comparable antileukemia reactivity was observed in vivo only when the inoculum of MLC-expanded cells was 2-3-fold higher than that of fresh spleen cells. This relative ineffectiveness was attributed to the altered migration pattern of cultured cells in vivo. IL-2-dependent cloned CTL, specific for a normal lymphocyte antigen (Qa-1b) also present on leukemia cells, were derived from MLC-expanded cultures and tested in vivo. For cloned CTL, as with MLC-expanded cells, eradication of AKR leukemia in vivo was associated with the tissue distribution pattern of the injected effector cells. That is, an effective antileukemia reaction was achieved only in tissues in which effector and target proximity was maintained. Qa-1b-specific cloned CTL did not interfere with engraftment of autologous or allogeneic bone marrow in lethally irradiated host mice, nor did they cause any clinically evident graft-versus-host disease. These findings suggest that cloned CTL specific for a normal cell surface antigen with limited host tissue distribution, but present on tumor cells, could be used for adoptive immunotherapy, provided CTL and tumor cell proximity can be attained.

Animals↗
PubMed1995

An efficient strategy for detection of known and new mutations of the CYP2D6 gene using single strand conformation polymorphism analysis.

To detect mutations in the cytochrome P450 CYP2D6 gene (CYP2D6), we developed a strategy based on single-strand conformation polymorphism (SSCP) analysis of the gene amplified by polymerase chain reaction (PCR). The efficiency of the method was evaluated by analysing DNA samples from extensive metabolizers (EM) and poor metabolizers (PM) of debrisoquine. Haplotypes, alleles and mutations of CYP2D6 had previously been characterized in each individual using PCR assays, Xba I restriction fragment length polymorphism (RFLP) and sequencing. PCR-SSCP results were in complete agreement with those obtained using established methods. All previously characterized mutations were associated with particular shifts in the electrophoretic mobility of DNA fragments allowing their identification. We further tested the efficiency of PCR-SSCP for detecting new CYP2D6 mutations. DNA from a PM subject presumed to carry an unknown non-functional mutant allele of CYP2D6 was amplified and bands with aberrant migration patterns were observed on SSCP gels. Sequence analysis of the corresponding DNA fragments revealed the causative mutations. In this way, a novel non-functional allele of the gene, carrying three previously reported mutations and a new mutation in the third exon which results in a premature termination codon, was characterized. Finally, CYP2D6 SSCP analysis was performed on DNA amplified with fluorescent primers and an automated DNA sequencer was used for SSCP analysis of products. We conclude that the PCR-SSCP approach is a powerful method of identifying simultaneously known and new mutations of the CYP2D6 gene.

Alleles↗
PubMed1997

The application of fluorescence-based PCR and PCR-SSCP to monitor the clonal relationship of cells bearing the t(14;18)(q32;q21) in sequential biopsy specimens from patients with follicle center cell lymphoma.

This study evaluates the utility of fluorescence-based polymerase chain reaction (PCR) and PCR-SSCP methodologies to monitor the clonal relatedness of cells with bcl-2 major break point region (mbr)/JR fusion sequences in sequential samples from patients with follicular lymphoma (FL). Fluorescence-tagged PCR products from 2-4 sequential samples from seven FL patients were resolved in acrylamide gels and analyzed on an Applied Biosystems' automated DNA sequencer equipped with Genescan software. The amplicons were sequenced directly using automated DNA sequencing to obtain the precise amplicon size and base sequence. Fluorescence-based PCR-single-strand conformation polymorphism (SSCP) analysis performed to distinguish amplicons of similar size but of different base sequence. Amplification products differing by as few as 5 bp resolved clearly under fluorescent PCR assay conditions making possible by visual inspection alone the distinction of two products that otherwise appeared to be of similar size by conventional gel electrophoretic methods. The size of the amplicons as determined by Genescan software correlated exactly with the sizes generated by sequence analysis confirming the precision and accuracy of the fluorescent PCR assay. Under nondenaturing conditions, the mobility profiles of the amplicons from sequential samples with identical base sequence remained indistinguishable, whereas amplicons of similar size but of dissimilar base sequence from different patients exhibited distinct migration patterns. Thus, this study demonstrates that a combination of fluorescent PCR and PCR-SSCP assays for the detection of the t(14;18) provides an accurate measure of clonal relationship based on molecular size and sequence similarities without involving radiolabeling and sequencing strategies. Furthermore, the demonstrated preservation of junctional sequences across sequential biopsy specimens validates the use of PCR in the monitoring of minimal residual disease and eliminates concern about the detection of secondary, non-tumor-related translocations.

Chromosomes, Human, Pair 14↗
PubMed2004

Surveillance of HIV-1 subtypes among heterosexuals in England and Wales, 1997-2000.

The molecular diversity and demographic characteristics among 976 anti-HIV-1-positive heterosexuals attending 15 sexually transmitted infection (STI) clinics participating in an unlinked anonymous HIV prevalence serosurvey in England and Wales during 1997-2000 were investigated. Subtypes were assigned by heteroduplex mobility assay or sequencing of the p17/p24 region of gag and the V3/V4 region of env and by sequencing of the protease gene. Overall, there was no significant change in the subtype distribution, with subtype C accounting for the majority (32%) of subtyped infections. Subtypes B (29%), A (12%), circulating recombinant forms (CRFs, 9%), unique recombinant forms (URFs, 8%), and subtypes D-H (8%) were also detected. Thirty-nine percent of infections in men were with subtype B, whereas subtype C was most common (38%) in women. Logistic regression analyses showed the relative risk (RR) of infection with a non-B subtype, compared with subtype B, to be greater in African-born individuals (RR = 28.9, P < 0.01), among newly diagnosed infections (RR = 3.4, P < 0.01), and in women (RR = 2.4, P < 0.01). These findings indicate a high level of genetic diversity among HIV-infected heterosexual STI clinic attendees in England and Wales. Recently, subtype C has become most prevalent, particularly in younger age groups, suggesting recent acquisition of this viral strain. The high proportion of non-B, CRF, and URF infections among UK-born individuals is consistent with mixing between migrants and UK-born individuals in England and Wales. As migration patterns change, continued monitoring of HIV genetic diversity will aid understanding of transmission patterns.

Africa↗
PubMed2006

The influence of surgical approach on cemented stem stability: an RSA study.

UNLABELLED: The surgical approach used is an important aspect of hip arthroplasty and will have an effect on the loading of the implant. Our goal was to establish whether there was a difference in early stem migration between the posterior and the lateral surgical approaches. The migration patterns of 45 Exeter stems in 45 patients were measured using radiostereometric analysis during a 2-year period; 19 of the stems were implanted using the posterior approach and 26 were implanted using the lateral approach. From postoperative radiostereometric measurements it was established that there was no difference in initial stem position between the two approaches. The posterior approach group had greater internal rotation of the stem, approximately 2 degrees during the first 2 years. The lateral group had almost 1/2 this amount of internal rotation. Overall stem subsidence was similar between the groups. These differences suggest that the lateral approach may give a survival advantage, especially for less rotationally stable stem designs and suboptimal cementing technique. The posterior approach gives rise to greater degree of internal rotation during the first 2 years. LEVEL OF EVIDENCE: Therapeutic Level II. See the Guidelines for Authors for a complete description of levels of evidence.

Aged↗