Clinical associations and risk factors for bleeding from colonic angiectasia: a case-controlled study.

AIM: A case-controlled study was performed to investigate the association of colonic angiectasia with other conditions and to identify risk factors for bleeding. METHOD: Information was collected from all patients who underwent colonoscopy at our hospital between January 2008 and December 2010. Data on 90 individuals with angiectasia [58 men; median age 69 (26-92) years] were compared with those of 180 individuals without angiectasia, matched for gender and age. RESULTS: Multivariate analysis showed that occult gastrointestinal bleeding [odds ratio (OR) 2.523; 95% confidence interval (CI) 1.238-5.142], liver cirrhosis (OR 13.195; 95% CI 3.502-49.711), chronic renal failure (OR 6.796; 95% CI 1.598-28.904) and valvular heart disease (OR 6.425; 95% CI 1.028-40.165) were identified as significant predictors of the presence of colonic angiectasia. Eight patients were diagnosed with bleeding from angiectasia. Cardiovascular disease (OR 22.047; 95% CI 1.063-457.345) and multiple angiectasias (P-value 0.0019) were identified as significant risk factors for active bleeding. Medication and a large size were not associated with an increased risk of bleeding. CONCLUSION: The presence of colonic angiectasia was associated with valvular heart disease, liver cirrhosis and chronic renal failure. Valvular heart disease and multiple lesions increased the risk of bleeding.

Simple biodosimetry method for cases of high-dose radiation exposure using the ratio of the longest/shortest length of Giemsa-stained drug-induced prematurely condensed chromosomes (PCC).

The aim was to develop a simple biodosimetry method for as rapid as possible estimation of absorbed radiation doses in victims of radiation accidents, in particular after high-dose exposure. Human peripheral blood lymphocytes (PBL) were gamma-irradiated in vitro with several doses up to 40 Gy stimulated with phytohaemagglutinin-P (PHA-P) for 2 days and their chromosomes condensed prematurely using 50 nm calyculin A. Chromosome lengths of Giemsa-stained G2 prematurely condensed chromosomes (PCC) were measured using image analysing software and the ratio of the longest/shortest chromosome length was calculated. The length ratio (LR) of the longest/shortest Giemsa-stained chromosome s increased with a good correlation to the square root of the radiation dose (D) up to 40 Gy, i.e. LR = (4.90 x D0.5) + 2.14. The LR of the longest/shortest chromosome might be used as an index for estimating the radiation dose. The blood samples should not be cooled until the start of separation/stimulation of the lymphocytes. A rapid and easy estimation of large doses after whole-body exposure was identified by measuring the ratio of the longest/shortest length of Giemsa-stained G2-PCC induced by calyculin A. This simple protocol will be particularly useful for making therapy decisions for victims of ionizing radiation exposure and has potential for use as a biodosimeter for partial-body exposure accidents.

Simple biodosimetry method for use in cases of high-dose radiation exposure that scores the chromosome number of Giemsa-stained drug-induced prematurely condensed chromosomes (PCC).

There is a need for quick dose estimation by a simple method in radiation accidents. This study develops a simple and rapid dose estimation protocol for victims of such accidents, in particular those involving high radiation doses. Human peripheral blood lymphocytes (PBL) were gamma-irradiated in vitro at several dose points up to 60 Gy, and were stimulated with phytohaemagglutinin-P (PHA-P) for 2 days to obtain dividing cells. PBL were then forced to condense prematurely, using 50 nM calyculin A, and the obtained chromosome spreads were Giemsa stained. The G2-PCC (prematurely condensed chromosomes) index and chromosome number for each radiation dose point were scored. G2-PCC were stably induced using calyculin A within 24 h delays in stimulation of PBL with PHA-P. The chromosome number of G2-PCC increased steeply with radiation doses up to 30 Gy at a rate of 0.31 Gy(-1) and then decreased at 0.30 Gy(-1) up to 40 Gy. More than 10% of G2-PCC index remained up to a 15 Gy dose. Even after 40 Gy irradiation, about 2% PCC index was obtained, and this value was enough to score a sufficient number of chromosome spreads for analysis. Therefore, the combined use of chromosome number and G2-PCC index allows biodosimetry to be done easily and rapidly. If PCC are not induced using calyculin A, it is strongly suggested that the radiation dose is over 50 Gy. A rapid and easy dose estimation for large dose exposure whole-body was realized by combined analysis of Giemsa-stained chromosome number of G2-PCC and PCC index using calyculin A. This simple method will be of use for rapid decision making of therapy for radiation accident victims. This method also has potential for use as a biodosimeter for partial-body exposure accidents.

Telomere size and telomerase activity in Epstein-Barr virus (EBV)-positive and EBV-negative Burkitt's lymphoma cell lines.

The telomere repeat lengths of BL cell lines were quantified by measuring terminal restriction fragment (TRF). Epstein-Barr virus (EBV)-positive Namalwa, Raji, and EB-3 cell lines have long telomeres, i.e. TRFs 10-19 kbp, whereas the Daudi cell line, producing a transformation-defective EBV mutant, has TRFs approximately 2.2 kbp. EBV-negative BJAB and DG75 cell lines have short TRFs 3.9-5.4 kbp, shorter than the approximately 12 kbp TRFs in PBLs. Telomerase activities of these BL cell lines are similar. TRFs of non-BL lymphoma cell lines are 2.3-5.5 kbp. Fluorescent in situ hybridization (FISH) studies of these cell lines showed remarkable heterogeneity of telomere size in chromosomes in the same BL cell. These results suggest that EBV-positive and EBV-negative BL cell lines have experienced various telomere dynamics.

Acetabular development after reduction in developmental dislocation of the hip.

A radiologic study was conducted on 56 patients with developmental dislocation of the hip (63 hips). Fifty hips in which neither acetabular nor femoral osteotomy was performed were classified as satisfactory (Severin Groups I and II) or unsatisfactory (Severin Groups III and IV) based on radiographs when growth was completed. The sequential changes in the center edge angle and the acetabular index were compared when the patients were ages of 5, 10, and 15 years. There was a significant relationship between the center edge angle and the acetabular index when the patients were 5 years of age and at final outcome. Most (85.7%) patients with a center edge angle less than 8 degrees and an acetabular index greater than 26 degrees at 5 years of age eventually were classified as Severin Groups III and IV at skeletal maturity. These findings suggest that radiologic results at the time when growth is completed can be predicted based on the center edge angle and the acetabular index in radiologic measurements at 5 years of age. The authors recommend that if at 5 years of age the center edge angle is less than 8 degrees and the acetabular index is greater than 26 degrees, consideration be given to an osteotomy to bring these values to a more normal range to improve final outcome.

High-LET radiation-induced aberrations in prematurely condensed G2 chromosomes of human fibroblasts.

PURPOSE: To determine the number of initial chromatid breaks induced by low- or high-LET irradiations, and to compare the kinetics of chromatid break rejoining for radiations of different quality. MATERIAL AND METHODS: Exponentially growing human fibroblast cells AG1522 were irradiated with gamma-rays, energetic carbon (290MeV/u), silicon (490MeV/u) and iron (200 and 600 MeV/u). Chromosomes were prematurely condensed using calyculin A. Chromatid breaks and exchanges in G2 cells were scored. PCC were collected after several post-irradiation incubation times, ranging from 5 to 600 min. RESULTS: The kinetics of chromatid break rejoining following low- or high-LET irradiation consisted of two exponential components representing a rapid and a slow time constant. Chromatid breaks decreased rapidly during the first 10min after exposure, then continued to decrease at a slower rate. The rejoining kinetics were similar for exposure to each type of radiation. Chromatid exchanges were also formed quickly. Compared to low-LET radiation, isochromatid breaks were produced more frequently and the proportion of unrejoined breaks was higher for high-LET radiation. CONCLUSIONS: Compared with gamma-rays, isochromatid breaks were observed more frequently in high-LET irradiated samples, suggesting that an increase in isochromatid breaks is a signature of high-LET radiation exposure.

Minimum 10-year results of Sugioka's osteotomy for femoral head osteonecrosis.

Sugioka's transtrochanteric rotational osteotomy was performed on 14 hips (12 patients) before 1987 for avascular necrosis of the femoral head involving a large part of the weight-bearing area. Three hips required a secondary total hip arthroplasty within 5 years after the osteotomy. The remaining 11 hips were examined at a mean of 13.2 years after surgery (range, 10-17.7 years). The clinical and radiologic results were related to the preoperative radiographic stage of the disease. In the hips with less than 2 mm of collapse, highly satisfactory results were maintained more than 15 years after surgery, with minimal development of degenerative changes. In hips with 2 mm or more of collapse or with acetabular changes, the results tended to deteriorate gradually during the long course of observation but were fairly acceptable. This study shows the osteotomy can enable hip joints to survive and function well for more than 10 years with proper patient selection and operative procedure.

Targeting double-strand breaks to replicating DNA identifies a subpathway of DSB repair that is defective in ataxia-telangiectasia cells.

The critical cellular defect(s) and basis for cell killing by ionizing radiation in ataxia-telangiectasia (A-T) are unknown. We use the topoisomerase I inhibitor camptothecin (CPT), which kills mainly S-phase cells and induces DSBs predominantly in replication forks, to show that A-T cells are defective in the repair of this particular subclass of DSBs. CPT-treated A-T cells reaching G2 have abnormally high levels of chromatid exchanges (viewed as prematurely condensed G2 chromosomes); aberrations in normal cells are mostly chromatid breaks. Transfectants of A-T cells with the wild-type ATM cDNA are corrected for CPT sensitivity, chromatid aberrations, and the DSB repair defect. These data suggest that in normal cells ATM, the A-T protein, probably recognizes DSBs in active replicons and targets the repair machinery to the breaks; in addition, the ATM protein is involved in the suppression of low-fidelity, adventitious rejoining between replication-associated DSBs. The loss of ATM functions therefore leads to genome destabilization, sensitivity to DSB-inducing agents and to the cancer-promoting illegitimate exchange events that follow.

Association between G2-phase block and repair of radiation-induced chromosome fragments in human lymphocytes.

We have studied the induction of chromosomal aberrations in human lymphocytes exposed in G0 to X rays or carbon ions. Aberrations were analyzed in G0, G1, G2 or M phase. Analysis during the interphase was performed by chemically induced premature chromosome condensation, which allows scoring of aberrations in G1, G2 and M phase; fusion-induced premature chromosome condensation was used to analyze the damage in G0 cells after incubation for repair; M-phase cells were obtained by conventional Colcemid block. Aberrations were scored by Giemsa staining or fluorescence in situ hybridization (chromosomes 2 and 4). Similar yields of fragments were observed in G1 and G2 phase, but lower yields were scored in metaphase. The frequency of chromosomal exchanges was similar in G0 (after repair), G2 and M phase for cells exposed to X rays, while a lower frequency of exchanges was observed in M phase when lymphocytes were irradiated with high-LET carbon ions. The results suggest that radiation-induced G2-phase block is associated with unrejoined chromosome fragments induced by radiation exposure during G0.

Valgus-extension osteotomy for advanced osteoarthritis in dysplastic hips. Results at 12 to 18 years.

We treated 31 consecutive patients of mean age 43 years (22 to 59) with severe osteoarthritis of the hip secondary to dysplasia by valgus-extension osteotomy. The clinical results were analysed for factors which may have affected the outcome. The procedure was carried out only on one side and was combined with a Chiari pelvic osteotomy in four patients. The angle of valgus was between 30 and 40 degrees with 10 to 20 degrees of extension. The mean follow-up was 15 years (12 to 18). Clinical evaluation using Charnley's modification of the system of Merle d'Aubigné and Postel showed that the mean score for pain had improved from 2.3 before operation to 4.2 at 15 years, and function from 2.3 to 4.2. Range of movement had decreased from 4.2 to 3.5. Fifteen patients (48.4%) had a pain score of 5 or 6 and were evaluated as satisfactory. Kaplan-Meier survivorship analysis showed a survival rate of 51% at 15 years after operation. Two preoperative factors had a significant positive correlation with the radiological results, namely the thickness of the capital drop osteophyte and the length of the roof osteophyte. We suggest that this procedure is effective for advanced osteoarthritis in the dysplastic hip in young and active patients if these factors are satisfactory on the preoperative radiographs.

[Telomere DNA and telomerase of lymphoma-derived cell lines--telomere hypothesis for cell growth control].

Telomere is the specialized structure of chromosome end. Telomeric DNA is essential for stabilization of linear double-stranded DNA molecules. Human telomeric DNA comprises the tandem repeat (AATGGG)n. Telomeres of normal somatic cells shorten progressively on every cell division, and telomere length is considered to determine cellular proliferative capacity. Most normal cells except germ line cells lack telomerase activity. Evidence of telomerase reactivation in human cancer cells was reported in 1994. The telomere hypothesis of aging and cell immortalization has drawn much attention in recent years. We examined telomere DNA and telomerase activity of Burkitt's lymphoma cell lines and EBV-infected proliferating B lymphocytes. All of these cells had varied average size of TRFs and the cell lines of lymphoma origin showed elevated telomerase activity.

Primary Charnley total hip arthroplasty for congenital dysplasia: effect of improved techniques of cementing.

We performed Charnley total hip arthroplasties on 64 patients (71 hips) between 1976 and 1984 for moderate congenital acetabular dysplasia in which a superolateral cement thickness of less than 20 mm was expected when the cup was placed in the true acetabulum at an angle of 45 degrees. Of these, 59 hips were examined 10 to 17 years after operation; 37 (group A) had been operated on between 1976 and 1982 using Charnley's original technique of cementing the acetabulum and 22 (group B) between 1983 and 1984 using more modern techniques. In group A, aseptic loosening of the socket was observed in ten hips (27.0%) and the 17-year survival rate was 81.5%. In group B, loosening was noted in only one socket (4.5%) and the 13-year survival rate was 100%. The improved techniques produced significantly better long-term results in fixation of the cup in dysplastic hips without bone grafting.

Total hip replacement using femoral neck bone to graft the dysplastic acetabulum. Follow-up study of 18 patients with old congenital dislocation of the hip.

We performed total hip replacement on 25 congenitally dislocated hips using corticocancellous bone from the femoral neck as a bone graft to reconstruct the deficient acetabulum. Two patients (two hips) died less than five years after surgery and three hips developed deep infection. We reviewed the remaining 20 hips at an average interval of 8.4 years (5.2 to 12.9). Their functional scores (modified Merle d'Aubigné and Postel) averaged 5.7 for pain, 5.1 for walking ability, and 4.2 for range of motion. Radiographs showed union and remodelling of the grafted bone in every case. There were radiological signs of aseptic loosening in three sockets (15%) without collapse of the grafted bone. None of the femoral stems was loose. No revision operation has been performed. Our results confirm the usefulness in the long term of femoral autografts for severe acetabular deficiency.

Regression of pulmonary and multiple skeletal metastases from renal cell carcinoma by nephrectomy and alpha-interferon therapy: a case report.

We report a rare case of advanced renal cell carcinoma in a patient who showed complete resolution of metastases to the lung and bones after nephrectomy, partial jejunectomy and subsequent alpha-interferon therapy. The patient was a 54-year-old man whose right lung and left femur metastases were detected before nephrectomy. In the seventh week after nephrectomy, a partial jejunectomy was carried out because of the obstructive ileus caused by intraluminal multiple metastases of the jejunum. A pathological fracture of the metastasized right humerus occurred subsequently. After four months of intramuscular alpha-interferon administration (3 x 10(6) units/day), however, x-rays revealed the complete disappearance of the metastatic lung shadow and a solid union of the humerus, and there were no tumor cells in the femur specimen resected at the subsequent reconstruction surgery of the left leg. Seven years have passed from onset, and the patient is still alive and disease free.

The pathogenesis of femoral head deformity in congenital dislocation of the hip. Experimental study of the effects of articular interpositions in pigs.

An experimental study was conducted based on the hypothesis that articular interpositions such as inverted limbi are major factors influencing deformities of the femoral head and neck that complicate treatment of congenital dislocation of the hip. In 24 neonatal pigs, the hip was fixed in a cast for one to three hours in the frog-leg position after insertion of an allogeneic meniscus into the hip joint. No macroscopic changes were observed immediately and one day after the above procedure, but electron microscopy showed degeneration of the cells in the physis. After 29-39 days, varus deformity and flattening of the femoral head were observed in all animals. After five months, marked deformity of the femoral head and replacement of the physis by fibrous tissue were noted. Angiograms obtained during cast fixation and 30 minutes after removal of the cast showed no circulatory occlusion. A short period of immobilization in the frog-leg position combined with articular interposition plays a major role in degeneration of the physis and predisposes to deformities of the femoral head and neck.

Tangential view arthrogram at closed reduction in congenital dislocation of the hip.

Of 119 previously untreated hips with congenital dislocation (complete dislocation), a classification of tangential view arthrograms at closed reduction was attempted in 34 joints that could not be reduced with a Pavlik harness or by traction but could be reduced manually under anesthesia. Conservative or open reduction was selected according to this classification. None of the hips had total femoral head necrosis, and only two femoral heads showed mild permanent necrosis. These results suggest the usefulness of this classification for selection of treatment for congenital hip dislocation.

Renin gene expression in the adrenal and kidney of patients with primary aldosteronism.

mRNA levels for renin in the adrenal gland and kidney were measured by ribonuclease protection assay (RPA). Renin mRNA was not detected by RPA in aldosteronoma and kidney tissues obtained from two patients with primary aldosteronism (PA). In these patients, the PRA values, plasma concentrations of active renin (ARC), and total renin (TRC = ARC + prorenin) were below the assay limit (less than 0.03 ng/L.s, 2.5 ng/L, and 10 ng/L, respectively). On the other hand, renin mRNA was recognized by RPA in aldosteronoma and kidney tissues obtained from two other patients with PA treated with 50 mg/day spironolactone for more than 2 months. Their TRC values were 49.8 and 16.6 ng/L, but their PRA and ARC were undetectable. Renin mRNA content was greater in normal adrenocortical tissue and in the normal kidneys obtained from three hypertensive patients with renal cell carcinoma. In these patients, the mean values of PRA, ARC, and TRC were 0.28 +/- 0.03 (mean +/- SD) ng/L.s, 18.4 +/- 7.8 ng/L, and 110 +/- 15 ng/L, respectively. This is the first report of the lack of renin gene expression in aldosteronoma and kidney tissues obtained from untreated patients with PA. Furthermore, treatment with spironolactone resulted in an increase in the levels of renin mRNA in the aldosteronoma and kidney tissues of patients with PA.

Hip joint instability in an infant with paraplegia following aortic surgery.

A report on an infant with paraplegia following aortic surgery who suffered from coarctation of the aorta and a ventricular septum defect (VSD). The spinal paralysis was complete and flaccid. He was found to have paralytic bilateral dislocatable hip joints. Magnetic resonance image (MRI) of spinal cord showed no pathological findings. The hip joints were treated by a hip abduction brace.