Comparison of High Hip Center versus Anatomical Reconstruction Technique in Crowe Types II and III Developmental Dysplasia of the Hip: a Retrospective Clinical Study.

PURPOSE OF THE STUDY The literature is conflicting as to whether the high hip center (HHC) reconstruction in total hip arthroplasty (THA) is an ideal option for patients with severe developmental dysplasia of the hip (DDH). This study aimed to compare the mid-term functional and radiographic outcomes of THA using HHC versus anatomical hip center (AHC) technique in Crowe types II and III DDH. Our hypothesis was that there may be no differences in terms of functional and radiographic outcomes between patients who underwent THA using HHC or AHC. MATERIAL AND METHODS Fifty-seven patients who underwent a primary THA due to Crowe type-II or type-III DDH were retrospectively reviewed and included. Patients were divided into two groups as per the hip center reconstruction: Group A (AHC technique) and group H (HHC technique). A cementless cup was inserted in 25 hips (19 female, 6 male; mean age = 51 years, age range = 28-67)) at near-AHC in group A and 32 hips (22 female, 10 male; mean age = 53 years, age range = 29-68) at HHC position in group H. To assess clinical status, the Harris Hip Score (HHS) was used at the final follow-up. In radiographical assessment, component loosening and osseointegration of the acetabular cup were examined on follow-up radiographs. Complications were also recorded. RESULTS The mean follow-up was 41 months (range, 25-84) in group A and 40 months (range, 24-86) in group H. The mean HHS was 83 (range, 74-91) in group A and 83.6 (range, 73-94) in group H (p = 0.741). Osteolysis was determined in three patients from each group. The other 51 cups demonstrated a minimum of one radiographic sign of osseointegration. Although the overall complication rate was higher in group A (64%) than in group H (46%), this difference reached no statistical significance (p = 0.11). CONCLUSIONS The HHC technique using cementless acetabular fixation seems to be a valuable alternative option to AHC technique in cases of Crowe types II and III DDH. Key words: High hip center; anatomical hip center; center of rotation; total hip arthroplasty; dysplastic hip; developmental dysplasia of the hip; Crowe type II; Crowe Type III.

Suppressed heat shock protein response in the kidney of exercise-trained diabetic rats.

Impaired expression of heat shock proteins (HSPs) and increased oxidative stress may contribute to the pathophysiology of diabetes by disrupted tissue protection. Acute exercise induces oxidative stress, whereas exercise training up-regulates endogenous antioxidant defenses and HSP expression. Although diabetic nephropathy is a major contributor to diabetic morbidity, information regarding the effect of HSPs on kidney protection is limited. This study evaluated the effects of eight-week exercise training on kidney HSP expression and markers of oxidative stress at rest and after acute exercise in rats with or without streptozotocin-induced diabetes. Induction of diabetes increased DNA-binding activity of heat shock factor-1, but decreased the expression of HSP72, HSP60, and HSP90. The inflammatory markers IL-6 and TNF-alpha were increased in the kidney tissue of diabetic animals. Both exercise training and acute exercise increased HSP72 and HSP90 protein levels only in non-diabetic rats. On the other hand, exercise training appeared to reverse the diabetes-induced histological changes together with decreased expression of TGF-beta as a key inducer of glomerulosclerosis, and decreased levels of IL-6 and TNF-alpha. Notably, HSP72 and TGF-beta were negatively correlated. In conclusion, impaired HSP defense seems to contribute to kidney injury vulnerability in diabetes and exercise training does not up-regulate kidney HSP expression despite the improvements in histopathological and inflammatory markers.

The protective effect of melatonin on sperm quality in rat after radioiodine treatment.

This study was designed to investigate the potential radioprotective impact of melatonin on the testicular tissue and sperm quality in rat given radioactive iodine (RAI) therapy. Thirty-six male Wistar albino rats were randomly divided into three groups as untreated control (Group 1); oral radioiodine group (RAI, 111 MBq, administrated rats); and RAI+melatonin group (oral radioiodine and intraperitoneal 12 mg/kg/day melatonin, starting 2 days before and continuing for 1 week after oral RAI administration). Twenty-four hours after the injection of the last melatonin dose, blood samples were taken for hormone analyses and the determination of the total antioxidant capacity. Sperm samples taken from the cauda epididymis were examined for spermatological parameters. Tissue samples taken from the rat testes were stained by TUNEL assay and with haematoxylin-eosin to detect apoptosis and histological alterations. It was demonstrated a significant decrease in epididymal spermatozoa viability and motility in all of the treatment groups, in comparison with the control group (p < .001). A significant decrease was also detected in sperm DNA fragmentation, follicle-stimulating hormone (FSH) level and the index of apoptotic germ cells in the RAI+melatonin group when compared to the radioiodine group. It was concluded that melatonin prevents the adverse affects of RAI on apoptosis and spermatozoa quality.

Evaluation of intra-testicular injections of calcium chloride and 4-vinylcyclohexene 1,2 monoepoxide for chemical sterilization in guinea pigs.

This study was aimed at investigating the use of intra-testicular calcium chloride (CaCl2) and 4-vinylcyclohexene 1,2-monoepoxide (VCM) injections as a side effect-free alternative method for the control of reproduction in guinea pigs. Fifty male guinea pigs were randomly assigned to five groups. In all groups, the chemical agents were injected into both testes in 1% lidocaine hydrochloride. While Groups I, II and III were administered with a single dose (0.25 mL) of sterile physiological saline, 15 mg/100 g CaCl2, and 240 mg/kg VCM, respectively, Group IV and V received a daily dose of 15 mg/100 g CaCl2, and 240 mg/kg VCM for 3 days, respectively. On day 90 post-administration, all animals were weighed and later decapitated under ether anaesthesia. Blood and tissue (testis, liver, hypophysis and adrenal gland) samples were taken. Sperm samples from the cauda epididymis were examined for spermatological parameters. Blood was used for hormone analyses and tissue samples were examined histopathologically (haematoxylin-eosin) and immunohistochemically (Tunel staining). The epididymal sperm count decreased in all treatment groups. Excluding 2 animals, Group V displayed azoospermia. When compared to the control group, Group V displayed the highest prolactin and lowest testosterone levels, and Group III showed the highest testosterone level. Histopathological examination revealed no intoxication finding. Chemical castration with VCM may be a good alternative to surgical castration as it enables mass sterilization without postoperative risks in guinea pig.

Biomechanical comparison of dynamic hip screw, proximal femoral nail, cannulated screw, and monoaxial external fixation in the treatment of basicervical femoral neck fractures.

PURPOSE OF THE STUDY The objective of this study was to establish relative fixation strengths of proximal femoral nail (PFN), dynamic hip screw (DHS), monolateral external fixator (EF), and cannulated screw (CS) in basicervical hip fracture model. MATERIAL AND METHODS The study involved four groups of implanted composite proximal femoral synthetic bones of eight specimens per group; nailing with PFN, DHS, fixation with three cannulated screws, and EF. 70˚ osteotomy was performed to simulate a Pauwels Type 3 basicervical fracture. Minimum preload of 100 N was applied before loading to failure. The constructs were subjected to cyclic loading with 16˚ to midline from 100 N to 1,000 N for 10,000 cycles at 3Hz. Axial loading was applied at 10 mm/min until failure. Failure load, failure mode, and displacement were documented. RESULTS Mean failure load was 2182.5 ± 377.9 N in PFN group, 2008.75 ± 278.4 N in DHS group, 1941.25 ± 171.6 N in EF group, and 1551.6 ± 236.2 N in CS group. Average displacement was 15.6 ± 4.5 mm, 15.5 ± 6.7 mm, 11.7 ± 1.9 mm, and 15 ± 1.7 mm, respectively. No significant difference was noted among groups for fixation strength except CS group. All CS constructs failed during cyclic loading. CONCLUSION Our findings suggest that PFN, DHS and EF achieved higher fixation strengths than CS in basicervical fracture. PFN has higher failure loads and possesses biomechanical benefits for fixation of unstable basicervical fractures compared with DHS and EF. Key words: basicervical fracture, internal fixation, biomechanics.

Elucidation of effect of spinopelvic parameters in degenerative disc disease.

INTRODUCTION: This study aims to find out if there is any relationship between disc pathology and spinopelvic morphology, respectively. METHODS: A total of 152 patients who complained about low back pain were assessed retrospectively. Patients were divided into three groups based on the presence of disc pathology: non-degenerative (ND) (n=34), degenerative disc disease (DDD) (n=80), and lumbar disc herniation (LDH) (n=38). Spinopelvic parameters were measured on the lateral standing radiographs using Surgimap® Software. The degree of degeneration of each disc was evaluated using T2-weighted images according to the Pfirmann classification. Correlation analyses were performed. RESULTS: No significant difference was observed between the three groups in terms of sagittal spinal and pelvic parameters. Age and BMI were positively correlated with DDD and LDH. PI and proximal lombar lordosis (PLL) were the only effective variables in predicting DDD. PT and distal lumbar lordosis (DLL) were found to be effective variables in predicting LDH. PI and PT values in patients with L1, L2, and L3 DDD were statistically significantly higher than those without degeneration (P<0.05). Although there were no statistical differences between PI and PT values (P>0.05), DLL values in L4 and L5 DDD patients were significantly lower than those without degeneration (P=0.041; P=0.046; P<0.05). CONCLUSIONS: The sagittal morphology of the spine directly influences the extent of lumbar disc degeneration. As the values of PI and PT increase, disc degeneration tends to occur at higher levels (L1-2-3). Disc degeneration at lower levels (L4-5) was associated with low DLL levels. LEVEL OF EVIDENCE: Level III, retrospective study.

Tumor Embolization through Meningohypophyseal and Inferolateral Trunks is Safe and Effective.

BACKGROUND AND PURPOSE: Skull base tumors are commonly supplied by dural branches of the meningohypophyseal and inferolateral trunks. Embolization through these arteries is often avoided due to technical challenges and inherent risks; however, successful embolization can be a valuable surgical adjunct. We aimed to review the success and complications in our series of tumor embolizations through the meningohypophyseal and inferolateral trunks. MATERIALS AND METHODS: We performed a retrospective review of patients with tumor treated with preoperative embolization at our institution between 2010 and 2020. We reviewed the following data: patients' demographics, tumor characteristics, endovascular embolization variables, and surgical results including estimated blood loss, the need for transfusion, and operative time. RESULTS: Among 155 tumor embolization cases, we identified 14 patients in whom tumor embolization was performed using the meningohypophyseal (n = 13) or inferolateral (n = 4) trunk. In this group of patients, on average, 79% of tumors were embolized. No mortality or morbidity from the embolization procedure was observed in this subgroup of patients. The average estimated blood loss in the operation was 395 mL (range, 200-750 mL). None of the patients required a transfusion, and the average operative time was 7.3 hours. CONCLUSIONS: Some skull base tumors necessitate embolization through ICA branches such as the meningohypophyseal and inferolateral trunks. Our series demonstrates that an effective and safe embolization may be performed through these routes.

Protective role of silibinin over nickel sulfate-induced reproductive toxicity in male rats.

Nickel damages the male reproductive system. We investigated the beneficial effects of silibinin which has metal-chelating and antioxidant properties over nickel toxicity. Both antioxidative effects in testes and overall effects related to sperm motility, membrane and acrosome integrity of orally administered Silibinin were evaluated against the harmful effects of 30 day of intraperitoneal nickel sulfate (5 mg/kg/day) administration in rats. Male rats were randomized into control (Group1; n=6) and three experimental groups (n=6, each): Group2 Nickel sulfate (5 mg/kg/day), Group3 Silibinin (150 mg/kg/day), and Group 4 Nickel sulfate (5 mg/kg/day) + Silibinin (150 mg/kg/day). We found higher sperm motility, viable sperm and total sperm count in Groups 3 and 4 than the Group 2 treatment groups and the percentage of abnormal spermatozoa was similar in both groups (Groups 2 and 4). Increased apoptosis, activation of caspase3, 8, 9 and TUNEL were detected in Group 2. However, activation of caspase3, 8, 9 and TUNEL was reduced in Group 4. The protective effects of silibinin were demonstrated on histopathologic findings and some sperm parameters (sperm motility percentage, viable spermatozoa, sperm count, and abnormal spermatozoa percentage) in rats exposed to nickel.

Olfactory dysfunction and coronavirus disease 2019 severity: a prospective cohort study.

OBJECTIVE: The primary goal of this study was to evaluate the association between olfactory dysfunction or taste impairment and disease severity and radiological findings in coronavirus disease-2019. The secondary goal was to assess the prevalence, severity and course of olfactory dysfunction or taste impairment in patients with coronavirus disease 2019. METHOD: This prospective observational cohort study evaluated patients hospitalised with coronavirus disease 2019 between April 1 and 1 May 2020. Olfactory dysfunction and taste impairment were evaluated by two questionnaires. Chest computed tomography findings and coronavirus disease-2019 severity were assessed. RESULTS: Among 133 patients, 23.3 per cent and 30.8 per cent experienced olfactory dysfunction and taste impairment, respectively, and 17.2 per cent experienced both. The mean age was 56.03 years, and 64.7 per cent were male and 35.3 per cent were female. No statistically significant association was found between olfactory dysfunction (p = 0.706) and taste impairment (p = 0.35) with either disease severity or chest computed tomography grading. CONCLUSION: Olfactory dysfunction or taste impairment does not have prognostic importance in patients with coronavirus disease 2019.

Exercise training and experimental diabetes modulate heat shock protein response in brain.

In diabetes, defense systems against cellular stress are impaired. Heat shock proteins (HSPs) function primarily as molecular chaperones. Factors that raise tissue HSP levels may slow progression of diabetes and improve diabetic complications that also affect brain tissue. This study tested the effect of an 8-week exercise training on brain HSP response in rats with or without streptozotocin-induced diabetes (SID). In untrained animals, the HSP levels were not different between SID and non-diabetic groups. Endurance training, however, increased HSP72 and HSP90 protein in non-diabetic rats, whereas SID significantly decreased the effect of training on these HSPs. At the mRNA level, HSP60, HSP90 and GRP75 were increased due to training, whereas HSP72 mRNA was only increased in exercise-trained diabetic animals. Training or diabetes had no effect on protein carbonyl content, a marker of oxidative damage. Altogether, our findings suggest that endurance training increases HSP expression in the brain, and that experimental diabetes is associated with an incomplete HSP response at the protein level.

SARS-CoV-2 infection of primary human lung epithelium for COVID-19 modeling and drug discovery.

Coronavirus disease 2019 (COVID-19) is the latest respiratory pandemic resulting from zoonotic transmission of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). Severe symptoms include viral pneumonia secondary to infection and inflammation of the lower respiratory tract, in some cases causing death. We developed primary human lung epithelial infection models to understand responses of proximal and distal lung epithelium to SARS-CoV-2 infection. Differentiated air-liquid interface cultures of proximal airway epithelium and 3D organoid cultures of alveolar epithelium were readily infected by SARS-CoV-2 leading to an epithelial cell-autonomous proinflammatory response. We validated the efficacy of selected candidate COVID-19 drugs confirming that Remdesivir strongly suppressed viral infection/replication. We provide a relevant platform for studying COVID-19 pathobiology and for rapid drug screening against SARS-CoV-2 and future emergent respiratory pathogens. ONE SENTENCE SUMMARY: A novel infection model of the adult human lung epithelium serves as a platform for COVID-19 studies and drug discovery.

A comparison of external fixation and locked intramedullary nailing in the treatment of femoral diaphysis fractures from gunshot injuries.

INTRODUCTION: We studied the safety and incidence of complications from the treatment of gunshot-induced femur diaphysis fractures with locked intramedullary nailing in comparison to external fixation. METHODS: Patients who had femoral diaphysis fracture operations due to gunshot injuries (107 femurs of 99 patients) between 2003 and 2014 were retrospectively reviewed, and 66 femurs of 60 patients were place into two groups (Group A: intramedullary nailing-38 femurs of the 36 patients; Group B: external fixator-28 femurs of 24 patients). The mean follow-up was 76.3 months (22-131). The study outcomes were patient complications, infection rate, union time, need for secondary surgery, functional assessment with lower extremity functional scale, and radiological evaluation with orthoroentgenograms. RESULTS: The mean age of the patients was 37.3 ± 7.4 years in Group A and 39 ± 6.1 years in Group B. There was no significant difference between the two groups in age, gender or follow-up. There were two deep infections (5.2%) in Group A and one deep infection (3.5%) in Group B. Delayed union was observed in four patients (10.5%) in Group A and in two patients (7.1%) in Group B. There was one non-union (2.6%) and one non-union (3.5%) in Group A and Group B, respectively. There was no significant difference between the two groups in incidence of union, delayed union or deep infection. The mean union time was 3.1 ± 2.5 months in Group A and 5.8 ± 1.4 months in Group B. The union time was significantly lower in the intramedullary nailing group (p = 0.023). There were no significant differences between the two groups in regards to radiological and functional evaluation. DISCUSSION: This study showed similar complication rates and functional results both for external fixator and intramedullary nailing for the treatment of femoral diaphysis fractures due to gunshot injuries. LEVEL OF EVIDENCE: Level 3 retrospective comparative clinical study.

The management of cubitus varus and valgus using the Ilizarov method.

Cubitus varus and valgus are the most common complications of supracondylar and lateral condylar fractures. Various combinations of osteotomy and fixation have been described to correct these deformities but each is associated with significant complications. In this study, we used distraction osteogenesis and Ilizarov frame fixation to treat 24 elbows in 23 patients with cubitus varus or valgus. Their clinical outcome was evaluated using the protocol of Bellemore et al. The mean time to follow-up was 18.3 months (10 to 36) and the mean time to frame removal was 13.5 weeks (8 to 20). The mean carrying angle was corrected from -18.7 degrees (-10 degrees to -30 degrees ) to 6.1 degrees (2 degrees to 10 degrees ) in patients with cubitus varus and from 36.5 degrees (25 degrees to 45 degrees ) to 9.4 degrees (4 degrees to 15 degrees ) in patients with cubitus valgus. There were 18 excellent and six good results. The Ilizarov method with gradual distraction is a safe, stable, adjustable and versatile method of treating deformities at the elbow without the problems of an unsightly scar or limited range of movement, and gives a good clinical and radiological outcome. Tardy ulnar nerve palsy should be treated first by anterior transposition.

Role of High-Resolution Dynamic Contrast-Enhanced MRI with Golden-Angle Radial Sparse Parallel Reconstruction to Identify the Normal Pituitary Gland in Patients with Macroadenomas.

BACKGROUND AND PURPOSE: Preoperative localization of the pituitary gland with imaging in patients with macroadenomas has been inadequately explored. The pituitary gland enhancing more avidly than a macroadenoma has been described in the literature. Taking advantage of this differential enhancement pattern, our aim was to evaluate the role of high-resolution dynamic MR imaging with golden-angle radial sparse parallel reconstruction in localizing the pituitary gland in patients undergoing trans-sphenoidal resection of a macroadenoma. MATERIALS AND METHODS: A retrospective study was performed in 17 patients who underwent trans-sphenoidal surgery for pituitary macroadenoma. Radial volumetric interpolated brain examination sequences with golden-angle radial sparse parallel technique were obtained. Using an ROI-based method to obtain signal-time curves and permeability measures, 3 separate readers identified the normal pituitary gland distinct from the macroadenoma. The readers' localizations were then compared with the intraoperative location of the gland. Statistical analyses were performed to assess the interobserver agreement and correlation with operative findings. RESULTS: The normal pituitary gland was found to have steeper enhancement-time curves as well as higher peak enhancement values compared with the macroadenoma (P < .001). Interobserver agreement was almost perfect in all 3 planes (κ = 0.89). In the 14 cases in which the gland was clearly identified intraoperatively, the correlation between the readers' localization and the true location derived from surgery was also nearly perfect (κ = 0.95). CONCLUSIONS: This study confirms our ability to consistently and accurately identify the normal pituitary gland in patients with macroadenomas with the golden-angle radial sparse parallel technique with quantitative permeability measurements and enhancement-time curves.

An alternative method for the treatment of nonunion of the tibia with bone loss.

In this retrospective study we evaluated the method of acute shortening and distraction osteogenesis for the treatment of tibial nonunion with bone loss in 17 patients with a mean age of 36 years (10 to 58). The mean bone loss was 5.6 cm (3 to 10). In infected cases, we performed the treatment in two stages. The mean follow-up time was 43.5 months (24 to 96). The mean time in external fixation was 8.0 months (4 to 13) and the mean external fixator index was 1.4 months/cm (1.1 to 1.8). There was no recurrence of infection. The bone evaluation results were excellent in 16 patients and good in one, while functional results were excellent in 15 and good in two. The complication rate was 1.2 per patient. We conclude that acute shortening and distraction osteogenesis is a safe, reliable and successful method for the treatment of tibial nonunion with bone loss, with a shorter period of treatment and lower rate of complication.

Novel burn device for rapid, reproducible burn wound generation.

INTRODUCTION: Scarring following full thickness burns leads to significant reductions in range of motion and quality of life for burn patients. To effectively study scar development and the efficacy of anti-scarring treatments in a large animal model (female red Duroc pigs), reproducible, uniform, full-thickness, burn wounds are needed to reduce variability in observed results that occur with burn depth. Prior studies have proposed that initial temperature of the burner, contact time with skin, thermal capacity of burner material, and the amount of pressure applied to the skin need to be strictly controlled to ensure reproducibility. The purpose of this study was to develop a new burner that enables temperature and pressure to be digitally controlled and monitored in real-time throughout burn wound creation and compare it to a standard burn device. METHODS: A custom burn device was manufactured with an electrically heated burn stylus and a temperature control feedback loop via an electronic microstat. Pressure monitoring was controlled by incorporation of a digital scale into the device, which measured downward force. The standard device was comprised of a heat resistant handle with a long rod connected to the burn stylus, which was heated using a hot plate. To quantify skin surface temperature and internal stylus temperature as a function of contact time, the burners were heated to the target temperature (200±5°C) and pressed into the skin for 40s to create the thermal injuries. Time to reach target temperature and elapsed time between burns were recorded. In addition, each unit was evaluated for reproducibility within and across three independent users by generating burn wounds at contact times spanning from 5 to 40s at a constant pressure and at pressures of 1 or 3lbs with a constant contact time of 40s. Biopsies were collected for histological analysis and burn depth quantification using digital image analysis (ImageJ). RESULTS: The custom burn device maintained both its internal temperature and the skin surface temperature near target temperature throughout contact time. In contrast, the standard burner required more than 20s of contact time to raise the skin surface temperature to target due to its quickly decreasing internal temperature. The custom burner was able to create four consecutive burns in less than half the time of the standard burner. Average burn depth scaled positively with time and pressure in both burn units. However, the distribution of burn depth within each time-pressure combination in the custom device was significantly smaller than with the standard device and independent of user. CONCLUSIONS: The custom burn device's ability to continually heat the burn stylus and actively control pressure and temperature allowed for more rapid and reproducible burn wounds. Burns of tailored and repeatable depths, independent of user, provide a platform for the study of anti-scar and other wound healing therapies without the added variable of non-uniform starting injury.

Fas mediated apoptosis of human Jurkat T-cells: intracellular events and potentiation by redox-active alpha-lipoic acid.

Activation of caspases is required in Fas receptor mediated apoptosis. Maintenance of a reducing environment inside the cell has been suggested to be necessary for caspase activity during apoptosis. We explored the possibility to potentiate Fas mediated killing of tumor cells by alpha-lipoic acid (LA), a redox-active drug and nutrient that is intracellularly reduced to a potent reductant dihydrolipoic acid. Treatment of cells with 100 microM LA for 72 h markedly potentiated Fas-mediated apoptosis of leukemic Jurkat cells but not that of peripheral blood lymphocytes from healthy humans. In Jurkat, Fas activation was followed by rapid loss of cell thiols, decreased mitochondrial membrane potential, increased [Ca2+]i and increased PKC activity; all these responses were potentiated in LA pretreated cells. PKCdelta played an important role in mediating the effect of LA on Fas-mediated cell death. In response to Fas activation LA treatment potentiated caspase 3 activation by over 100%. The ability of LA to potentiate Fas mediated killing of leukemic cells was abrogated by a caspase 3 inhibitor suggesting that increased caspase 3 activity in LA-treated Fas-activated cells played an important role in potentiating cell death. This work provides first evidence showing that inducible caspase 3 activity may be pharmacologically up-regulated by reducing agents such as dihydrolipoic acid.

Activated Akt expression in breast cancer: correlation with p53, Hdm2 and patient outcome.

Activation of protein kinase-B/Akt (pAkt) is mediated by oestrogen and involves HER-2 in vitro, to phosphorylate Hdm2 and influence p53 cytoplasmic localisation and degradation. Expression of all active Akt isoforms (pAkt) were examined, together with p53/Hdm2 subcellular expression in invasive ductal breast cancers (IDCs), to evaluate whether in vitro findings were related to clinical data and determine the effect on outcome. Immunohistochemical expression of serine 473 specific phosphorylated Akt (pAkt) isoforms (Akt-1,2,3) was evaluated in 97 patients, together with subcellular expression of p53/Hdm2. The results show that pAkt was evaluable in 95 patients with cytoplasmic expression in 81% and more likely to be associated with larger tumours (P=0.007), with no correlation with HER-2 expression. pAkt correlated with increasing levels of cytoplasmic p53 (P=0.025) and was associated with a reduced disease-free survival (P=0.04; univariate). In conclusion, pAkt has implications in breast cancer growth through mechanisms inactivating p53 with an association with immunohistochemical p53 expression, which is preferentially cytoplasmic. Despite in vitro associations, pAkt appears to be a variable marker of HER-2 expression.