Morphometric geometrical analysis to determine the centre of the acetabular component placement in Crowe type IV hips undergoing total hip arthroplasty.

AIMS: We analyzed the acetabular morphology of Crowe type IV hips using CT data to identify a landmark for the ideal placement of the centre of the acetabular component, as assessed by morphometric geometrical analysis, and its reliability. PATIENTS AND METHODS: A total of 52 Crowe IV hips (42 patients; seven male, 35 female; mean age 68.5 years (32 to 82)) and 50 normal hips (50 patients; eight male, 42 female; mean age 60.7 years (34 to 86)) undergoing total hip arthroplasty were retrospectively identified. In this CT-based simulation study, the acetabular component was positioned at the true acetabulum with a radiological inclination of 40° and anteversion of 20°. Acetabular shape and the position of the centre of the acetabular component were analyzed by morphometric geometrical analysis using the generalized Procrustes analysis. RESULTS: The acetabular shapes of Crowe IV hips were distinctively triangular; the ideal position of the centre of the acetabular component was superior on the posterior bony wall. The first and second relative warps explained 34.2% and 18.4% of the variance, respectively, compared with that of 28.6% and 18.0% in normal hips. We defined the landmark as one-third the distance from top on the posterior bony wall in Crowe IV hips. The average distance from the centre of the acetabular component was 5.6 mm. CONCLUSION: Crowe IV hips are distinctively triangular; the point one-third from the top on the posterior bony wall was a useful landmark for placing the acetabular component.

Safe zone for transacetabular screw fixation using a Kerboull cross-plate: A CT-scan templating prospective study.

BACKGROUND: Implantation of Kerboull acetabular reinforcement cross-plates (Kerboull plate) carries a risk for injury to vascular structures and pelvic organs. To our knowledge, there is no study assessing anatomical assessment related to this risk with this specific design. Therefore, we performed a prospective study to answer the following four questions: 1) What is the minimum distance and angle between the plate and iliac vessels? 2) What is the distance between the plate and the inner cortex of the ilium? 3) What is the ratio of views with muscle tissue present on the inner surface of the ilium? 4) What are the boundaries of the safe zone for transacetabular screw fixation for a Kerboull plate? HYPOTHESIS: A safe zone for fixation screws would be defined by a narrow range of insertion angles. MATERIALS AND METHODS: This is a CT-based 3D templating prospective study. Simulations were performed for 18 patients fitted with a Kerboull plate. An original Kerboull plate (Stryker, Mahwah, NJ, USA) was placed at a 45° abduction angle relative to the X-axis (alignment A) and the palette was placed vertically to the X-axis (alignment B). We measured the distance from the centre of the plate to the inner surface of the cortex of the ilium, the shortest distance to vessels and the angle of existing vessels, and the ratio of muscles on the inner surface of the ilium. RESULTS: The shortest distance to the vascular structures increased with increasing angle of insertion of the fixation screws, 85.8±12.1mm for A and 111.4±12.0mm for B at 45°. The distance to the inner cortex was further increased for screws inserted in posterior direction. At insertion angles ≥40°, the screws passed through muscle before invading the pelvis in most cases. However, at anterior-posterior angle (AP angles) ≤-10°, the risk of direct insertion of screws into the sacroiliac joint increased. DISCUSSION: The safe zone for transacetabular screws would be insertion at an angle≥40°, with an AP angle between 0° and -10° (slight posterior direction). LEVEL OF EVIDENCE: Level IV prospective diagnostic study.

The use of the transverse acetabular ligament in total hip replacement: An analysis of the orientation of the trial acetabular component using a navigation system.

It has recently been reported that the transverse acetabular ligament (TAL) is helpful in determining the position of the acetabular component in total hip replacement (THR). In this study we used a computer-assisted navigation system to determine whether the TAL is useful as a landmark in THR. The study was carried out in 121 consecutive patients undergoing primary THR (134 hips), including 67 dysplastic hips (50%). There were 26 men (29 hips) and 95 women (105 hips) with a mean age of 60.2 years (17 to 82) at the time of operation. After identification of the TAL, its anteversion was measured intra-operatively by aligning the inferomedial rim of the trial acetabular component with the TAL using computer-assisted navigation. The TAL was identified in 112 hips (83.6%). Intra-observer reproducibility in the measurement of anteversion of the TAL was high, but inter-observer reproducibility was moderate. Each surgeon was able to align the trial component according to the target value of the angle of anteversion of the TAL, but it was clear that methods may differ among surgeons. Of the measurements of the angle of anteversion of the TAL, 5.4% (6 of 112 hips) were outliers from the safe zone. In summary, we found that the TAL is useful as a landmark when implanting the acetabular component within the safe zone in almost all hips, and to prevent it being implanted in retroversion in all hips, including dysplastic hips. However, as anteversion of the TAL may be excessive in a few hips, it is advisable to pay attention to individual variations, particularly in those with severe posterior pelvic tilt.

beta-Catenin gene mutation in human hair follicle-related tumors.

beta-Catenin, a multifunctional protein related to the adherens junction and to signal transduction, is a key molecule of cell proliferation, and it is central to epithelial architecture, regulating the polarity of cells and tissues. beta-Catenin stabilization may play a key role in epidermal signaling leading to hair development, and its aberrant activation may be implicated in formation of hair tumors. Several investigators have shown that pilomatricomas are frequently associated with beta-catenin mutation. In this study, we confirmed beta-catenin gene (CTNNB1) mutation in human pilomatricomas (100% frequency) from which adequate DNA could be obtained for gene analysis. A novel mutation, D32N, was found in one case of pilomatricoma. A preliminary immunohistological study revealed prominent beta-catenin staining in basophilic cells of pilomatricomas, especially in nuclei. Benign tumors which were considered to be derived from hair matrix or hair follicles, and other benign skin tumors, were also investigated. beta-Catenin mutations were not detected in any of the these tumors. These results seem to indicate that hair matrix cells are key players in hair development. Investigation into gene abnormalities of hair-follicle tumors may elucidate the cause of their neoplastic transformation, and may provide a suggestion for the mechanism of hair development.

Coronary risk factors in acute Kawasaki disease: correlation of serum immunoglobulin levels with coronary complications.

BACKGROUND: To determine the usefulness of the IgG z-score (age and sex-standardized serum IgG level) before intravenous gamma globulin therapy (IVGG) in predicting the occurrence or severity of coronary complications in Kawasaki disease (KD). METHODS: A case-control study of clinical and laboratory findings with 88 children in the early stage of acute KD who received IVGG (100 or 200 mg/kg for 2-5 days) therapy. Of these, 20 cases had persistent coronary arterial lesions (small aneurysm, moderate aneurysm or large aneurysm persisting more than 1 month). The controls comprised 68 children with no coronary aneurysms or transient small aneurysm only observed within 1 month after the onset of KD. The association between serum levels of immunoglobulin G (IgG). IgM, IgA as well as other coronary risk factors previously reported and the occurrence of the coronary arterial lesions was evaluated using logistic regression analysis. RESULTS: After adjustment for age, gender, total IVGG dose before the 9th illness day and other traditional coronary risk factors, the odds ratio for the persistent coronary aneurysm associated with lower serum IgG z-score (< -0.7485 vs > or = -0.7485), was 30.3 (95% confidence interval, 3.8-243.2). Furthermore, the serum IgG z-score was inversely correlated with the severity of the coronary arterial lesion. CONCLUSIONS: The IgG z-score before IVGG therapy in the early stage of KD provides useful information on the risk factors for persistent coronary aneurysm and is a novel, additional indicator for therapy to prevent the coronary complications in acute KD.

Fas- and perforin-independent mechanism of cytotoxic T lymphocyte.

Cytotoxic T lymphocytes (CTLs) play an important role in elimination of virus-infected cells (1). Recent studies revealed at least two distinct mechanisms that CTLs utilize to destroy their target cells. Both mechanisms induce target cell apoptosis specifically and directionally, but these processes are totally different. One is pore formation on target cell membrane by perforin secreted from CTLs (perforin-granzyme pathway), and the other is ligation of Fas, which is expressed on the surface of target cells and Fas ligand, on the surface of CTLs (Fas-FasL pathway) (2). Here we review our work and describe CTL clones that have novel lytic mechanisms derived from CD4-CD8- lymph node cells of gld mice.

Structure-based design and characterization of exocyclic peptidomimetics that inhibit TNF alpha binding to its receptor.

Exocyclic small peptidomimetics corresponding to three critical binding sites of tumor necrosis factor (TNF)-receptor(I) have been designed based on atomic features deduced from the crystal structures of TNF alpha and the TNF beta/TNF-receptor(I) complex and a model of an anti-TNF alpha monoclonal antibody. TNF alpha antagonistic activities were evaluated by binding assays using soluble receptor or intact receptor on cells as well as an apoptosis/cytotoxicity assay. The most critical interaction site for rational design of peptidomimetics was localized to the loop1/domain3 of the TNF-receptor. The best antagonist showed 5 microM inhibition in the binding assay. Biologically, the mimetics inhibited TNF alpha-mediated apoptosis.

Relationship of p215BRCA1 to tyrosine kinase signaling pathways and the cell cycle in normal and transformed cells.

We have analysed the relationship of the products of two genes, neu and BRCA1, known to be important in human breast cancer. Highly specific antibodies that recognized both the rodent and human form of the BRCA1 gene product (Mr 215 kDa, p215BRCA1) were developed to facilitate these efforts. p215BRCA1 was identified as a tyrosine phosphorylated protein primarily localized in the nucleus of several breast cancer cell lines. In transformed murine and human cells, levels of p215BRCA1 tyrosine phosphorylation were inversely correlated with the activity of the erbB family receptor-tyrosine-kinases and with the transformed growth features of these cells. Regulation of p215BRCA1 tyrosine phosphorylation was also related to events in the cell cycle. Increased levels of p215BRCA1 phosphotyrosine content were observed in NIH3T3 cells arrested at the G2/M transition. These findings indicate that the products of BRCA1, neu, and erbB breast cancer genes participate in a common or shared signaling pathway important in cell growth and its regulation.

Csk overexpression reduces several monokines and nitric oxide productions but enhances prostaglandin E2 production in response to lipopolysaccharide in the macrophage cell line J774A.1.

The catalytic activity of src-family protein tyrosine kinases (src-PTK) is suppressed when a C-terminal tyrosine is phosphorylated by an intracellular PTK, C-terminal Src kinase (Csk). In the present report, to study the regulatory functions of the Csk in cells of monocyte/macrophage lineage, we transfected a eukaryotic expression vector containing rat csk cDNA in a macrophage cell line, J774A.1, and examined alterations of the response to lipopolysaccharide (LPS) in the transfectants which overexpressed Csk. Csk overexpression resulted primarily in a down-regulation of Fgr activity, an src-PTK expressed in J774A.1, and hyperphosphorylation of several cellular proteins of 35, 57, 66, 97 and 120-130 kDa. Furthermore, in these Csk transfectants, production of interleukin (IL)-1alpha, IL-6, tumor necrosis factor-alpha, and nitric oxide (NO) following LPS stimulation were reduced compared with those in parental J774A.1 or J774A.1 transfected with the vector alone. The extent of reduction paralleled the amounts of Csk proteins expressed in the Csk-transfected J774A.1. The reduced NO production in these cells was associated with low levels of mRNA of inducible NO synthetase. On the other hand, an enhancement of prostaglandin E2 production was observed in the Csk-transfected J774A.1 cells upon stimulation with LPS, which appeared to result from the high level of prostaglandin-H synthetase in the transfectants. The present findings indicate that overexpression of Csk has differential effects on the regulation of production of chemical mediators and monokines, probably via modulation of signal transduction downstream of LPS-mediated signals.

Determination of left to right shunt by thermodilution in patients with ventricular septal defect.

A modified thermodilution technique was used to determine the quantity of shunt in patients suffering from congenital heart disease with a left to right shunt. In our modification, the thermistor was placed within the pulmonary artery and an indicator was injected into both sides of the heart. In a series of 33 cardiac catheterizations in children (1-17 years) with ventricular septal defect (VSD), pulmonary blood flow (Qp), systemic blood flow (Qs) and the ratio of Qp to Qs (Qp/Qs) were determined by this and ordinary oximetry (Fick) methods. Correlation coefficients between indexes obtained by these methods were 0.54 (Qp), 0.78 (Qs), and 0.75 (Qp/Qs). The estimates of Qp and Qp/Qs obtained by thermodilution were smaller than those obtained by the Fick method. This modification of thermodilution is simple, rapid, and useful in clinical practice.

A case of acute rheumatic fever: echocardiographic findings for mitral regurgitation in acute rheumatic carditis.

An eight-year-old girl with mitral regurgitation in acute rheumatic fever was examined by echocardiography. The examination showed posterior displacement of the coaptation point of the anterior mitral leaflet, i.e. anterior mitral prolapse, and did not indicate signs of edematous change or verrucous fibrin deposits on the valves. Mitral valve prolapse is thought to be one of the causes of mitral regurgitation in acute rheumatic carditis.

Quantification of blood pressure tracking of children by tracking index: the Shimane Heart Study.

The tracking of systolic blood pressure (SBP) was analyzed in a cohort of children. The study population consisted of 1009 Japanese children in Izumo City, a rural community in the northwest of Honshu. There were 252 subjects in cohort (C)-1, 235 in C-2, 286 in C-3, 131 in C-4 and 105 in C-5. Follow-up periods were from 6 to 9 years of age in C-1, 9 to 12 in C-2, 12 to 15 in C-3, 6 to 12 in C-4 and 9 to 15 in C-5. BP was measured by conventional method. Tracking index (TI) was calculated as follows: TI = (2x + y - z)/N/.24; x, y and z are numbers of subjects who remained at the same quintile, who moved to the next quintile and who moved to a remote quintile, respectively; N = x + y + z; TI becomes 1.0 when SBP changes randomly. SBP tracking was apparent in both sexes of C-1 (TI = 2.4 in boys, 2.5 in girls), in girls of C-2 (TI = 3.5), in both sexes of C-3 (TI = 3.2 in boys, 2.7 in girls) and in girls of C-4 (TI = 4.1) and C-5 (TI = 3.3). TI agreed well with the tracking phenomena visualized by distribution bar graph. We conclude that TI can assess the degree of tracking quantitatively and can be applied to analysis of the tracking phenomena of BP and its related factors.

Tracking of blood pressure, height, weight and left ventricular muscle volume in children--the Shimane Heart Study.

Two cohorts of Japanese children were studied longitudinally at 3-year intervals, at ages 6 and 9 years in cohort 1 and 9 and 12 years in cohort 2. There were 252 children in cohort 1 and 235 in cohort 2. The examinations performed were blood pressure, height, weight, skin fold thickness, upper arm length and circumference, ECG, VCG, M-mode echocardiography, serum cholesterol, hemoglobin and urinalysis. The subjects were divided into 5 quintile groups by their systolic blood pressure (SBP) percentiles calculated at each examination. SBP was tracked in each cohort throughout the follow-up period. Percentages remained in the highest SBP quintile group at both examinations were 43.5% (boys) and 59.1% (girls) in cohort 1, and 25.0% (boys) and 56.5% (girls) in cohort 2. The tracking of SBP was defined by body mass (height and weight) in most children. In some children, however, it was not defined by body mass tracking. Left ventricular muscle volume and its index were large in boys in the highest SBP tracking group. This indicates that the cardiac muscle is hypertrophied already, before the development of hypertension.

Heart diseases discovered by mass screening in the schools of Shimane Prefecture over a period of 5 years.

Mass screening by ECG for heart diseases in pupils and students was performed in Shimane Prefecture; all the children had primary screening and were under the supervision of a pediatric cardiologist in all phases, from primary to precise (tertiary) examination. The precise examination was performed with 2D echo, exercise ECG and/or cardiac catheterization when indicated, and an important feature of this mass screening was the ability to carry out an accurate follow-up in all the phases from primary to precise examination. The number of subjects in the primary screening from 1980 to 1984 was 50758 primary school pupils, 44216 junior high school students and 33480 senior high school students; organic heart diseases not under the supervision of the pediatric cardiologist at the time of mass screening were found in 22 primary school pupils (0.04% of participants in the primary screening), 14 junior high school students (0.03%) and 5 senior high school students (0.01%). Clinically significant arrhythmias without underlying organic heart diseases were discovered by mass screening in 8 primary school pupils (0.02%), 13 junior high school students (0.02%) and 16 senior high school students (0.05%).

Transmural conduction velosity index in healthy schoolchildren.

Transmural conduction velosity index (TCVI) was obtained in 174 healthy children. TCVI was defined as the echocardiographically determined interventricular septal thickness (IVST) divided by the ventricular activation time (VAT) measured by body surface potential mapping. TCVI ranged from 14 to 49 cm/sec and was highly correlated with IVST (r = 0.75, TCVI = 3.25 X IVST + 0.56). It was concluded that the left ventricular hypertrophy with muscular thickness does cause the greater conduction velosity in healthy children.

Mass survey for coronary lesions in school children with history of Kawasaki disease in Shimane Prefecture.

In 1981, a mass survey for Kawasaki disease was performed in Shimane Prefecture. The incidence of the disease was 0.3% in elementary and 0.1% in junior high schools, respectively. The number of children with a past history of Kawasaki disease was 40. Selective coronary arteriography (S-CAG) was performed on 37 children by December 1983 and 3 cases having coronary lesions were detected. In all these 3 children, more than 8 years had elapsed since the onset of the disease and in one of them there were severe stenotic changes in the coronary artery, with coexisting mitral incompetence. Two-dimensional echocardiography (2D echo) was able to detect dilatatory coronary lesions, but it failed to delineate stenotic changes adequately in these 3 cases. The present data indicate that 2D echo cannot demonstrate the stenotic segments of the coronary artery and therefore S-CAG is necessary for that purpose. We suggest coronary arteriography (CAG) for school children with a past history of Kawasaki disease.

The relationship between blood pressure and left ventricular muscle volume in normal children and adolescents--the Shimane Heart study.

Blood pressure (BP) and left ventricular muscle volume (LVMV) were measured in 408 children and adolescents aged 9-15 years. LVMV was determined by M-mode echocardiography. Lean body weight was approximately calculated using body weight, upper arm circumference and triceps skin fold thickness. Lean-BSA was obtained by substituting lean body weight for body weight in the formula for BSA. Subjects were divided into the high and the low BP percentile groups according to their BP percentile values. LVMVI (= LVMV/BSA) and lean-LVMVI (= LVMV/L-BSA) were compared between the two groups. LVMVI and L-LVMVI were larger in the high BP percentile group than in the low one. Regression lines of LVMV to BSA were also compared between the two groups. Regression lines of the high BP percentile group were located in a higher position than those of the low percentile group. These results suggest that LVMV are larger in the high BP percentile group than in the low percentile group even if their BSAs are equal. We concluded that left ventricular hypertrophy has been already initiated in the pre-hypertensive stage of human beings as observed in spontaneously hypertensive rats.

Computer analysis of frank vectorcardiograms in normal children--maximal spatial QRS vector.

Frank vectorcardiograms recorded on magnetic tape were analyzed by a computer. The study population was 835 normal children aged from 6 to 16. Magnitudes, angles (azimuth, elevation) of the maximal spatial QRS vector and QRS duration were calculated. The magnitude of maximal spatial QRS vector increased significantly in males compared to those in females at ages 9-10, 11-12 (p less than 0.01) and 15-16 (p less than 0.001). Though there was no significant difference of elevation in either sex, azimuth tended to move more anteriorly in females than in males. QRS duration in males became longer with increasing age, while in females at age 15-16, it decreased (p less than 0.001).