Associations between components of the metabolic syndrome versus bone mineral density and vertebral fractures in patients with type 2 diabetes

The association of bone with the metabolic syndrome and its features, visceral fat accumulation or insulin resistance, remains unclear. We determined visceral and subcutaneous fat areas (V and S) by computed tomography on 187 men (28–83 years) and 125 postmenopausal women (46–82 years) with type 2 diabetes. Men whose V was 100 cm² or more had significantly lower urinary N-terminal cross-linked telopeptide of type-I collagen (p = 0.005), higher femoral neck bone mineral density (FN-BMD) (p = 0.004), and lower prevalence of vertebral fractures (VFs) (p = 0.04) than controls. Fat mass, V, S, and lean body mass positively correlated with FN-BMD in men and with lumbar (L) and FN-BMD in women. When adjusted for weight, these correlations became negative. Urinary C-peptide positively correlated with FN-BMD in both genders. Multivariate logistic regression analysis adjusted for age, height, weight, L-BMD, duration of diabetes, and diabetes therapies identified V in men and urinary C-peptide in women as factors inversely associated with the presence of VFs [odds ratio (OR) = 0.61 per SD increase, p = 0.04, and OR = 0.32, p = 0.01, respectively]. These findings suggest that, of the components of the metabolic syndrome, body fat in gravity and hyperinsulinemia could increase FN-BMD in diabetic subjects. Visceral fat in men and hyperinsulinemia in women may protect against VFs independent of weight, L-BMD, diabetes duration, or therapies.     

Significance of lateral biopsy specimens during transrectal ultrasound-guided prostate biopsies in Japanese men

OBJECTIVES: Lateral biopsies are thought to have a better cancer detection rate compared with standard sextant biopsies. This study aimed to determine whether lateral peripheral zone biopsies in Japanese men who underwent transrectal ultrasound-guided prostate biopsies provided a significantly higher cancer detection rate than sextant biopsies. METHODS: Between 1999 and 2004, data were collected from 461 men who underwent prostate biopsy and had enough data regarding the performance of lateral biopsies for statistical analysis. There were two categories in this study: (i) patients who underwent sextant prostate biopsies; and (ii) patients who underwent sextant biopsies plus lateral biopsies. RESULTS: Prostate cancer was detected in 141 (30.6%) of 461 patients. It was detected in 24 (22.2%) of 108 patients who underwent sextant biopsies and 117 (33.1%) of 353 patients who underwent sextant plus lateral biopsies. Lateral biopsies were not associated with a statistically higher rate of positive biopsy findings; however, we found a significantly higher ratio of patients with positive findings in those with prostate specific antigen (PSA) levels 10 ng/mL (one of 71, 1.4%) among those who had positive cores only in lateral biopsy samples (P < 0.0001). CONCLUSIONS: Lateral biopsies did not show a significantly higher detection ratio of prostate cancer compared to sextant biopsies. However, lateral biopsies were more effective than sextant biopsies in patients with lower PSA levels. Our findings might be useful for the establishment of biopsy strategies to detect prostate cancer, especially in patients with lower PSA levels.     

Regulatory mechanisms of growth hormone secretion are sexually dimorphic.

Sexually dimorphic growth hormone (GH) secretory pattern is important in the determination of gender-specific patterns of growth and metabolism in rats. Whether GH secretion in humans is also sexually dimorphic and the neuroendocrine mechanisms governing this potential difference are not fully established. We have compared pulsatile GH secretion profiles in young men and women in the baseline state and during a continuous intravenous infusion of recombinant human insulin-like growth factor I (rhIGF-I). During the baseline study, men had large nocturnal GH pulses and relatively small pulses during the rest of the day. In contrast, women had more continuous GH secretion and more frequent GH pulses that were of more uniform size. The infusion of rhIGF-I (10 microg/kg/h) potently suppressed both spontaneous and growth hormone-releasing hormone (GHRH)-induced GH secretion in men. In women, however, rhIGF-I had less effect on pulsatile GH secretion and did not suppress the GH response to GHRH. These data demonstrate the existence of sexual dimorphism in the regulatory mechanisms involved in GH secretion in humans. The persistence of GH responses to GHRH in women suggests that negative feedback by IGF-I might be expressed, in part, through suppression of hypothalamic GHRH.     

Clinical and pathological evaluations of methotrexate, vinblastine, Adriamycin and cisplatin chemotherapy for advanced urothelial cancers

We have treated advanced transitional-cell carcinoma of the urothelial tract with methotrexate, vinblastine, Adriamycin, and cisplatin (M-VAC) chemotherapy since July of 1985. We analyzed the effect of that chemotherapy in 26 patients with advanced urothelial cancer who were treated in our hospital and followed up. They were divided into two groups. Group 1 consisted of 15 patients with distant metastases. In all, 11 of them received M-VAC as adjuvant chemotherapy for metastatic lesions after surgical removal of the primary lesion, and the remaining 4 patients were not operable since they had very advanced-stage tumors; they received only M-VAC chemotherapy. Group 2 contained 11 patients who received M-VAC neo-adjuvant chemotherapy. In group 1, the overall response rate was 57.1% and the mean duration of response was 12.6 months. In the 11 patients who had received M-VAC as adjuvant therapy after surgical removal of the primary tumor, the mean duration of response was 14.1 months. After M-VAC chemotherapy, six patients underwent surgical resection of metastatic lesions and restaging was done pathologically in these cases. The clinical response coincided with the pathological response in all six cases. In group 2,5 of 11 patients experienced histological downstaging of the resected bladder. M-VAC chemotherapy combined with surgical resection of residual tumors has proved to be an effective option against advanced urothelial cancer.Presented at the 4th International Conference on Treatment of Urinary Tract Tumors with Adriamycin/Farmorubicin, 16–17 November 1990, Osaka, Japan     

Immediate changes in subcellular structures of transplanted tumors following photodynamic and laser hyperthermic therapy

Background and Objective: To further understand the precise process of the tumor cell degeneration after photodynamic therapy (PDT), laser hyperthermic therapy (LH), and combined treatments using an Nd:YAG laser. It is important to examine initial morphological alteration of tumor cells after these treatments. Study Design/Materials and Methods: In this study, nude mice bearing HeLa cell tumors were treated with PDT, LH, and combined treatments of the two. Tumor tissues obtained immediately after these treatments were analyzed using electron microscopy and morphometry. Results: In the combined treatments, which produced more severe effects on tumor cells, morphological features of apoptosis such as cytoplasmic condensation, blebs, and apoptotic bodies appeared in the cells, although the typical alteration in the nuclear chromatin was not seen. Conclusion: Cytoplasmic alterations may proceed more rapidly than nuclear alterations in the cellular degeneration induced by the single or combined treatments of PDT and LH.     

Innate immunity and its role against infections.

LEARNING OBJECTIVES: This article reviews current concepts of the innate immune system that offers protection against infections. It offers an overview for the readers to understand how innate immunity, consisting of different receptors, cells, and mediators recognizes pathogens and exerts protective function against pathogens. DATA SOURCES AND STUDY SELECTION: MEDLINE-search articles including original research papers, review articles, textbooks, and references identified from bibliographies of relevant articles. RESULTS AND CONCLUSIONS: The innate immune system is nonspecific immunity present since birth not requiring repeated exposure to pathogens. It is capable of differentiation between self and nonself. Because of its nonspecificity, it has a broad spectrum of resistance to infection. Further, it is thought to play an important role in the control of adaptive immunity by regulating co-stimulatory molecules and effector cytokines. Innate immunity includes pattern recognition molecules/receptors, antimicrobial peptides, the complement system, inflammatory mediators, and cytokines produced by immune cells. Pattern recognition molecules/receptors recognize pathogen-associated molecular patterns that are essential for microorganisms' survival and pathogenicity. Although innate immunity has recently gained increasing importance, further studies are necessary for a better understanding of its role.     

Effects of intrathecal and intraperitoneal morphine on gastrointestinal motility in the rat.

A method has been developed to compare gastrointestinal (GI) transit time after intrathecal (i.t.) drug injection in the rat. Each animal had a catheter implanted in the i.t. space. Eight rats, on three separate occasions, had either i.t. morphine 16 micrograms kg-1 (in 50 microliters) or intraperitoneal (i.p.) morphine (0.1%) 7.5 mg kg-1 or i.t. saline (50 microliters). The dose of morphine was the ED50 for analgesia by each route. After halothane and oxygen anaesthesia, 10 steel balls and 1 ml of contrast medium were placed into the stomach, the whole procedure being completed within 5 min. Radiographs were taken at 5 min, 3, 6 and 24 h, and the number of balls in the stomach, small and large intestine were counted. The inhibitory effect of i.t. or i.p. morphine on gut motility caused an equally significant delay at 6 h. In a separate series of eight rats the delay by i.t. morphine could be completely antagonized by i.p. naloxone 1 mg kg-1. Thus, i.t. morphine in an analgesic dose even though smaller than the i.p. dose has a similar inhibitory effect on GI tract motility in the rat. This method would enable comparisons on GI transit to be made between a variety of intrathecally administered drugs.     

The value of frequent positioning of treatment field in radiotherapy of esophageal cancer]

Since 1983 a clinical trial of proton beam radiotherapy has been conducted at the Proton Medical Research Center (PMRC) of the University of Tsukuba. We have made it a rule to do field localization by X-ray pictures before each treatment. For this purpose we have developed a localize-verify system consisting of a fluoroscopic unit and a real time digital image processing device. By using this system as well as X-ray films, field placement errors or corrected distance at field localization were measured in 11 patients with esophageal cancers. Measurements of corrected distances on a total of 177 localization attempts disclosed that correction by > 5 mm was necessary in 30.6% and by > 10 mm in 10.2% of all localization attempts. Corrected distances appeared to increase with age, possibly because the skin becomes looser and ambulatory status tends to be more limited in older patients. Field placement corrections of more than 5 mm were required in 66.7% of 60 localizations in patients > 80 years old. Two patients in whom the anatomical positions of the esophagus were easily movable are presented. The following common characteristics of these patients were considered high risk factors: they were more than 80 years old; lesions were located in the lower esophagus; and they had T1 tumors. These findings suggested that frequent positioning and verification of treatment fields are necessary in the accurate treatment of esophageal cancers, especially those in high-risk patients.