The correlation between Salter's criteria for avascular necrosis of the femoral head and Kalamchi's prognostic classification following the treatment of developmental dysplasia of the hip.

AIMS: The aim of this study was to evaluate the correlation between Salter's criteria and Kalamchi's classification of avascular necrosis in patients treated for developmental dysphasia of the hip (DDH). PATIENTS AND METHODS: The study involved a retrospective analysis of 123 patients (123 hips) with DDH treated by operative and non-operative reduction before the age of two years, with a minimum follow-up of ten years. Salter's criteria (S1 to S4) were determined from radiographs obtained at one to two years post-reduction, whilst the Kalamchi grade was determined from radiographs obtained at ten or more years of age. Early post-reduction radiographs were also used to evaluate the centre-head distance discrepancy (CHDD) and the occurrence of a dome-shaped deformity of the proximal femoral metaphysis (D-shaped metaphysis). The prognosis was described as good (Kalamchi grade K0 or KI), fair (Kalamchi grade KII) or poor (Kalamchi grade KIII or KIV) for analysis and correlation with the early Salter criteria, CHDD and D-shaped metaphysis. RESULTS: S1 and S2 criteria were predictive of a poor prognosis. The outcome following S3, S4 and S3 + S4 varied; 18 (40%) had a good prognosis, 17 (38%) a fair prognosis and ten (22%) a poor prognosis. A CHDD ≥ 10% and a D-shaped metaphysis were also predictive of a poor prognosis. CONCLUSION: The Salter criteria were predictive of the Kalamchi grade of avascular necrosis in patients with DDH aged ten or more years after reduction of the hip. Cite this article: Bone Joint J 2017;99-B:1115-20.

Development of prostate cancer in a patient with primary hypogonadism: intratumoural steroidogenesis in prostate cancer tissues.

Intratumoural steroidogenesis may play a significant role in the progression of prostate cancer (PC) in the context of long-term ablation of circulating testosterone (T). To clarify the mechanism accounting for the progression of PC in a 74-year-old man who had undergone bilateral orchiectomy when he was 5 years old, we performed immunohistochemical studies of androgen receptor (AR) and steroidogenic enzymes in the prostate. We also measured steroid hormone levels in the serum and prostate, as well as mRNA levels of genes mediating androgen metabolism in the prostate. Positive nuclear staining of AR was detected in malignant epithelial cells. The levels of androstenedione (Adione), T, and 5-alpha dihydrotestosterone (DHT) in the serum of the patient were similar to those in PC patients receiving neoadjuvant androgen deprivation therapy (ADT), but were higher in the patient's prostate than in PC patients not receiving ADT. The gene expression of CYP17A1 and HSD3B1 was not detected, whereas that of STS, HSD3B2, AKR1C3, SRD5A1, and SRD5A2 was detected. Moreover, cytoplasmic staining of HSD3B2, AKR1C3, SRD5A1, and SRD5A2 was detected in malignant epithelial cells. Hence, in the present case (a man with primary hypogonadism), steroidogenesis in PC tissues from adrenal androgens, especially dehydroepiandrosterone sulphate, was the mechanism accounting for progression of PC. This mechanism might help elucidate the development of castration-resistant PC.

Induction of microRNAs, mir-155, mir-222, mir-424 and mir-503, promotes monocytic differentiation through combinatorial regulation.

Acute myeloid leukemia (AML) involves a block in terminal differentiation of the myeloid lineage and uncontrolled proliferation of a progenitor state. Using phorbol myristate acetate (PMA), it is possible to overcome this block in THP-1 cells (an M5-AML containing the MLL-MLLT3 fusion), resulting in differentiation to an adherent monocytic phenotype. As part of FANTOM4, we used microarrays to identify 23 microRNAs that are regulated by PMA. We identify four PMA-induced microRNAs (mir-155, mir-222, mir-424 and mir-503) that when overexpressed cause cell-cycle arrest and partial differentiation and when used in combination induce additional changes not seen by any individual microRNA. We further characterize these pro-differentiative microRNAs and show that mir-155 and mir-222 induce G2 arrest and apoptosis, respectively. We find mir-424 and mir-503 are derived from a polycistronic precursor mir-424-503 that is under repression by the MLL-MLLT3 leukemogenic fusion. Both of these microRNAs directly target cell-cycle regulators and induce G1 cell-cycle arrest when overexpressed in THP-1. We also find that the pro-differentiative mir-424 and mir-503 downregulate the anti-differentiative mir-9 by targeting a site in its primary transcript. Our study highlights the combinatorial effects of multiple microRNAs within cellular systems.

Long-term results of surgical therapy for masticatory muscle tendon-aponeurosis hyperplasia accompanied by limited mouth opening.

Masticatory muscle tendon-aponeurosis hyperplasia is a new disease entity characterized by limited mouth opening due to contracture of the masticatory muscles, resulting from hyperplasia of tendons and aponeuroses. In the case of masseter muscle type, the face displays a square mandible configuration. Pharmacotherapy, occlusal splints and physical therapy are ineffective. This study evaluated the long-term results of aponeurectomy of the masseter muscle with coronoidectomy to release the temporal muscle tendon. The subjects were 10 patients who underwent surgery between 2000 and 2005. Mean maximum mouth opening before surgery was 21.8mm (range 17-29 mm). All patients received bilateral aponeurectomy of the masseter muscle and coronoidectomy. Three patients additionally underwent bilateral anglectomy for esthetic reasons. After discharge, one patient did not return to the hospital. Data from the other nine patients were analyzed. The mean duration of follow-up was 4 years. At final follow-up, the maximum mouth opening was >44 mm in four patients, 40-44 mm in three patients, and 35-39 mm in two patients. Overall satisfaction was excellent or good in all patients.

[Schizophrenia and ocular misalignment: phenotypic and genetic association analysis].

The increased incidence of minor physical anomalies (MPAs) in schizophrenia is the fundamental basis for the neurodevelopmental hypothesis of schizophrenia etiology. Ocular misalignment falls into the category of MPAs, but this phenotype has not been assessed in schizophrenia. This study reveals that constant exotropia displays marked association with schizophrenia. To assess the genetic mechanisms, we examined the transcription factor genes ARIX and its paralogue, PMX2B. We identified frequent deletion/insertion polymorphisms in the 20-alanine homopolymer stretch of PMX2B, with a modest association between these functional polymorphisms and constant exotropia in schizophrenia. The polymorphisms were also associated with overall schizophrenia and more specifically with schizophrenia manifesting strabismus. These results suggest a possible interaction between PMX2B and other schizophrenia-precipitating factors, increasing the risk of the combined phenotypes. This study also highlights the unique nature of the polyalanine length variations found in PMX2B.

Alternating myocardial sympathetic neural function of athlete's heart in professional cycle racers examined with iodine-123-MIBG myocardial scintigraphy.

Myocardial sympathetic neural function in professional athletes who had the long-term tremendous cardiac load has not been fully investigated by myocardial iodine-123-metaiodobenzylguanidine (MIBG) uptake in comparison with power spectral analysis (PSA) in electrocardiography. Eleven male professional cycle racers and age-matched 11 male healthy volunteers were enrolled in this study. The low frequency components in the power spectral density (LF), the high frequency components in the power spectral density (HF), the LF/HF ratio and mean R-R interval were derived from PSA and time-domain analysis of heart rate variability in electrocardiography. The mean heart-to-mediastinum uptake ratio (H/M ratio) of the MIBG uptake, in professional cycle racers was significantly lower than that in healthy volunteers (p < 0.01) and HF power in professional cycle racers was significantly higher than that in healthy volunteers (p < 0.05). In the group of professional cycle racers, the H/M ratio showed a significant correlation with the R-R interval, as indices of parasympathetic nerve activity (r = 0.80, p < 0.01), but not with the LF/HF ratio as an index of sympathetic nerve activity. These results may indicate that parasympathetic nerve activity has an effect on MIBG uptake in a cyclist's heart.

Detection of malignant tumors: whole-body PET with fluorine 18 alpha-methyl tyrosine versus FDG--preliminary study.

PURPOSE: To compare the diagnostic potential of whole-body positron emission tomography (PET) with fluorine 18 alpha-methyl tyrosine (FMT) with that of whole-body PET with 2-[fluorine 18]fluoro-2-deoxy-D-glucose (FDG). MATERIALS AND METHODS: Nineteen patients with or suspected of having malignant tumors and five healthy volunteers underwent whole-body PET with FMT and FDG. RESULTS: In comparison with FDG uptake, FMT uptake was significantly less in the brain, heart, lung, liver, and spine. On a lesion-by-lesion basis, the sensitivity of whole-body FMT PET for depicting malignant tumors was inferior to that of whole-body FDG PET, but this difference was not statistically significant (74% [26 of 35 lesions] vs 91% [32 of 35 lesions], P >.05). The positive predictive value of FMT PET was superior to that of FDG PET (87% [26 of 30 lesions] vs 63% [32 of 51 lesions], P <.001). The difference in uptake between benign and malignant lesions was significant with FMT PET (mean +/- SD, 1.64 +/- 0.96 vs 0.79 +/- 0.23; P <.001) but not with FDG PET (5.02 +/- 3.56 vs 4.02 +/- 2.90, P >.05). CONCLUSION: Whole-body FMT PET is clinically useful in the diagnosis of malignant tumors and may be effective in the depiction of primary and metastatic lesions in the cardiac region or in the brain.

Accuracy of standardized uptake value measured by simultaneous emission and transmission scanning in PET oncology.

We assessed the accuracy of the standardized uptake value (SUV) measured by simultaneous emission and transmission scanning in cancer patients using FDG positron emission tomography (PET). Conventional, independent emission (E)/transmission (T) scans and simultaneous E/T scans were conducted consecutively in 30 patients who underwent FDG PET examinations. The SUVs of 35 mass lesions and 34 selected normal tissues were derived from the independent E/T scan and simultaneous E/T scan. Experimental studies using a cylindrical phantom were also conducted to evaluate the accuracy and reproducibility of the SUV derived from a simultaneous E/T scan. The SUVs of 18F solution in the phantom were estimated to be approximately 1, with high reproducibility in the range of total counts observed in the clinical examinations. There were no significant differences in the SUVs in 35 tumours derived from simultaneous E/T scans and those derived from independent scans, and there was a strong positive correlation between the two (r = 0.99, P < 0.01). There were also no significant differences in the SUVs in 34 normal tissue regions derived from simultaneous E/T scans and those derived from independent scans. In conclusion, simultaneous E/T scanning with FDG in patients with malignant tumours is a valid method, since the SUV derived from the simultaneous scan is accurate and reproducible.

New superselective intra-arterial infusion via superficial temporal artery for cancer of the tongue and tumour tissue platinum concentration after carboplatin (CBDCA) infusion.

We developed a new technique of superselective intra-arterial chemotherapy for tongue cancer using a modified (1.35 mm) angiographic catheter. The catheter was confirmed to be inserted into the lingual artery by the new technique. We measured the platinum concentrations in resected tumour tissues after infusion of carboplatin (CBDCA) at 20 mg/m2 over 30 min from 30 min before tumour resection in 12 patients with cancer of the tongue (6 patients: superselective intra-arterial infusion; 6 patients: conventional intra-arterial infusion). The mean platinum concentration in tumour tissue was 10.5 +/- 1.2 micrograms/g wet, which was more than twice higher than, and significantly different from, 4.3 +/- 3.8 micrograms/g wet by the conventional intra-arterial infusion method. This new superselective intra-arterial infusion method allows direct infusion of the anticancer agent into the artery supplying the tumour and is expected to become a new therapeutic modality for cancer of the tongue.

Chemo-endocrine therapy in patients with stage D2 prostate cancer.

There have only been a few studies of chemo-endocrine therapy compared with endocrine therapy alone in newly diagnosed prostate cancer patients. We assessed the effects of these two therapies by comparing long-term survival rates. One hundred and twenty-nine patients were entered in this study between November 1977 and March 1992. Seventy-seven patients were treated with endocrine therapy alone. Other 52 patients received chemo-endocrine therapy, which included orchiectomy and/or diethylstilbestrol diphosphate (DES-DP) plus Cisplatin, with or without other cytotoxic agents. All patients had bone metastasis at the beginning of the study. There was a significant difference in survival between patients who received endocrine therapy and chemo-endocrine therapy (P = 0.0078). That is, survival rate was superior for the chemoendocrine therapy patients throughout the entire follow-up period. These data suggest that early chemo-endocrine therapy containing Cisplatin, with or without maintenance chemotherapy, is a potentially effective treatment for newly diagnosed metastatic prostate cancer and is worth further investigation via a randomized trial.

[The significance of six sextant biopsy for prostate cancer].

The significance of six sextant ultrasound guided biopsies of the prostate (SS-biopsy) was evaluated in a total of 114 patients. The presence of prostate cancer was suspected (Pca) in 59 subjects through mass screening (MS) for Pca and in 47 patients in out-patient clinics (OPC). The recurrence (REC) was suspected in 3 patients diagnosed previously as Pca. All of them had elevated PSA, abnormal digital rectal examination (DRE) and/or abnormal transrectal ultrasonography (TRUS). All of these tests in 5 patients with benign prostate hypertrophy (BPH) were normal. Moreover, in 34 patients among them, oriented biopsies were performed to the area where Pca was suspected by DRE and or TRUS. Twelve Pca patients were detected in MS group (20.3%), 17 Pcas in OPC group (36.2%) and 3 Pcas in REC group (100%). No Pca patients were detected in BPH group. In 12 Pca patients with T1 or T2, only one Pca patient (8.3%) had over 3 Pca samples among the samples obtained by SS-biopsy. In 20 patients with T3 or T4, 13 patients (65%) had over 3 Pca samples. There was significant relationship between T category and Pca sample numbers among 6 samples obtained by SS-biopsy (p < 0.01). Ten of 12 Pca patients in MS group (83.3%) and 8 of 17 patients in OPC group (47.1%) had less 3 Pca samples. Pca was detected in 9 of 34 patients examined by the oriented biopsy. However al of these Pca were detected by SS-biopsy. It may be not necessary to examine Pca suspected patients by the oriented biopsy if they were examined by this SS-biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Mass screening for prostate cancer and the bias relating to survival rate.

Since 1981 we have been studying prostate cancer (Pca) by mass screening (MS) in the Gunma Prefecture, Japan. From 1981 to 1990, 9,067 subjects (total 15,451) were examined in connection with this project and 121 subjects were diagnosed as having Pca. The presence of Pca in 87 cases was confirmed at their initial MS (initial group); 34 cases were confirmed either the year after or several years after the first MS (repeat group). To evaluate the significance of MS for Pca, in this group of patients, the effects of 'lead time bias', 'self-selection bias' and 'length bias' on the survival rate were compared to Pca patients detected in the hospitals of the Gunma Prefecture during the same period. The survival curves of MS cases for each stage of the disease were better than those of the controls. Only in stage D was there a significant difference between the two groups. However, this MS curve decreased from the 4th year in the same manner as the control curve from the start. The clinical characteristics (age, pathological differentiation, prostatic acid phosphatase, gait disturbance, erythrocyte sedimentation rate, chronic disease, and pain in the patients with stage D disease) were compared between both groups. All characteristics studied, except age, in the MS group were clinically more favorable compared to those of the controls for each stage or in total. Moreover, the relative survival rate of subjects examined by MS was greater than 1.0. No significant difference was found in stage distribution between the initial group and the repeat group.(ABSTRACT TRUNCATED AT 250 WORDS)

Bilateral renal angiomyolipoma associated with bilateral renal vein and inferior vena caval thrombi.

We report a case of bilateral renal angiomyolipoma with thrombosis of the bilateral renal veins and inferior vena cava. Right partial nephrectomy and total thrombectomy were performed. To our knowledge only 5 cases of invasion of the inferior vena cava have been described. We report a case in which the renal veins were involved bilaterally. Treatment modalities are discussed.

[Prostatic specific antigen (PA) in mass screening for prostate cancer].

The usefulness of prostatic specific antigen (PA) was compared with that of prostatic acid phosphatase (PAP). PA was determined in the serum of 2,183 patient examined by the mass screening for prostate cancer from 1987 to 1990. The serum samples of these patients were obtained from our serum bank. PA was measured by the E test "TOSOH" II (PA). The relationship of PA and PAP to prostate size estimated by digital rectal examination (DRE) and ultrasound tomography (US), and age was investigated. PA and PAP correlated with aging and prostate size estimated by DRE. However PA was more apparently related with these things. The correlation between PA and prostatic size estimated by US was relatively high (r = 0.53), but the correlation between PAP and prostate size estimated by US was low (r = 0.20). When the upper limit of normal range was set at 6.0 ng/ml, the sensitivity, specificity and efficiency was 64%, 97% and 62%, respectively. PA was more sensitive than PAP and could be more useful since none of the patients with prostate cancer was PAP positive and PA negative. We conclude that PA should be a reliable tumor marker in our mass screening system.

[Significance of prostatic specific antigen in the mass screening for prostate cancer].

The significance of prostatic specific antigen (PSA) was investigated in the subjects examined by the mass screening for prostate cancer from 1985 to 1990. All subjects was examined by digital rectal examination (DRE) and with prostatic acid phosphatase (PAP) and the subjects in whom prostate cancer (Pca) was suspected from abnormal DRE and/or elevated PAP were recommended to receive the secondary screening to confirm the presence of Pca. PSA was measured by radioimmunoassay using Ball-Elsa-PSA-kit. 1,600 serum samples were obtained from our serum bank. The relationship among PSA, prostate size estimated by DRE and age was investigated. PSA was increased with age and the prostate size, PSA being more closely related with the latter. Therefore, we estimated that PSA has an ability to detect benign prostatic hypertrophy (BPH) in the mass screening. This estimation should be confirmed by using an ultrasound tomography because the prostate size obtained by DRE is inaccurate as compared with that obtained by ultrasound tomography. The cut off level of PSA was determined by control which was composed from the subjects with normal size prostate and one with BPH. When the cut off level was 8.6 ng/ml, the sensitivity, specificity and efficiency as Pca marker was 73.9%, 97.4% and 97.1%, respectively. PSA was more than 8.6 ng/ml in all of Pca with elevated PAP. PSA was expected to improve the Pca detection rate in our mass screening system.

Significance of a new stratification of alkaline phosphatase and extent of disease in patients with prostate carcinoma with bone metastasis.

Bone is the most frequent site of metastatic prostate cancer and the prognosis of patients with bone metastasis is poor. The authors have investigated a semiquantitative system to evaluate bone metastatic lesions in terms of cancer-specific survival. Based on the extension of disease (EOD) grade proposed by Soloway and associates, a new EOD grading system obtained from bone scintigraphy alone and EOD score obtained from bone scintigraphy and alkaline phosphatase was studied in 164 patients with prostate cancer with metastatic bone involvement. In terms of a cancer-specific survival and prostate cancer death, both the new EOD grade and the EOD score were apparently superior to eight other items studied (age, medical score, gait disturbance, histologic grade, erythrocyte sedimentation rate, prostatic acid phosphatase, and alkaline phosphatase). Multivariate analysis revealed that the EOD score was better than the new EOD grade. This improvement was due to the elimination of false-positive or nonactive metastatic bone lesions on bone scintigraphy through the alkaline phosphatase evaluation.

[Voiding disturbance in elderly males examined by prostate mass screening. Gunma Urological Oncology Study Group].

Information about voiding disturbance was obtained from 34,140 elderly males in Gunma Aged Club Association (Q group) through a questionnaire and from 8,129 males by prostate mass screening for prostate disease (MS group) as to: (1) the characteristics of the subjects examined by the mass screening, (2) the relationship between the voiding disturbance and aging and (3) the frequency of voiding disturbance in the normal elderly males. In MS group, the percentage of young subjects, especially less than 60 years old, who complained voiding disturbance was higher than the expected percentage on the assumption that it increases with aging. The percentage of voiding disturbance in these young subjects was also higher than that of males in the same decade in Q group. In their past and present history, the percentage of benign prostatic hypertrophy (BPH) in these young subjects was higher than the expected percentage on the assumption that the incidence of BPH increases with aging. Judging from these results, it was estimated that they were not satisfied with the medical care by which they were treated or were being treated, and they received this mass screening to obtain consultation for their complains. Loss of the force was related with the prostate size estimated by digital rectal examination but not with aging. However, nocturia was well related with aging but not with the prostate size. Hesitancy, strain and dribbling were not apparently related with either the prostate size or aging. It was demonstrated that frequency of nocturia was 0 to 1 in less than 60 years old normal males, 0 to 2 in 60 to 79 years old ones and 0 to 3 in over 80 years old ones. The other symptoms studied in each decade were also analyzed and discussed.

A comparative study of diazepam levels in bone marrow versus serum, saliva and brain tissue.

The distribution of diazepam in biological fluids and tissues of rats was examined 1, 2, 4 and 8 h after intraperitoneal administration by using a radioimmunoassay with specific anti-diazepam antibody. The diazepam levels in serum, saliva, brain and bone marrow decreased over a period of 2 h and levelled off 4 h after administration. The diazepam concentration in bone marrow was much higher than in serum, saliva and brain, suggesting an accumulation of diazepam in this tissue. This indicates that bone marrow could be a very useful material for the detection of diazepam in skeletonized remains. The diazepam concentrations in bone marrow, serum, saliva and brain showed a linear relationship (r = 0.860-0.997), indicating that a valid estimate of diazepam concentration in blood can be made from bone marrow samples.

The significance of erythrocyte sedimentation rate as a prognostic factor for patients with prostate cancer: Gunma Urological Oncology Study Group investigation.

The Gunma Urological Oncology Study Group has performed a multivariate statistical analysis of prognostic factors based on 353 patients with prostate cancer diagnosed between 1974 and 1984. This paper discusses the prognostic significance of erythrocyte sedimentation rate (ESR) in these patients with prostate cancer. Based on three ranges (less than 20, greater than 20- less than 50, greater than 50 mm/h) of ESR, a significant difference of survival rates among the patients was found by means of univariate analysis. ESR apparently includes components which represent anemia or infection. Hemoglobin, frequently used as a prognostic factor, was compared with ESR by means of multivariate analysis, and ESR was found to be a more useful prognostic factor than hemoglobin. Moreover ESR showed the highest partial coefficient value among the items studied (clinical stage, pathological differentiation, age, acid phosphatase, gait disturbance). It seems that ESR includes not only anemia and infection components but also provides a clue to the degree of bone metastasis or the degree of prostate cancer progression.

[The analysis of prognostic factors for prostate cancer by multivariate analysis].

Multivariable analysis (quantification method I and II) was used to investigate the relationship between survival rates and prognostic factors. The items studied were age, stage, pathological differentiation, gait disturbance, acid phosphatase and erythrocyte sedimentation rate (ESR). The data were available for 353 patients for all items. The significance of each item was evaluated in all patients-group, subgroup stratified by their cause of death, and subgroup stratified by their stage. The significance of age and gait disturbance which represent the general condition was proven in all patients, non-cancer death group and stage ABC group. In the cancer death group, stage D group was the most significant as prognostic factor. ESR was the most significant in the stage D group and the significance was gradually increased with the observation time.