Monocyte chemoattractant protein 1 is correlated with glycemic control and peripheral arterial disease in type 2 diabetic patients with metabolic syndrome.

We evaluated the serum levels of monocyte chemoattractant protein 1 (MCP-1) and their association with peripheral arterial disease (PAD) in 199 patients with type 2 diabetes mellitus (T2DM) and metabolic syndrome ([MetS], group A) in comparison with 109 healthy controls (group B). In group A, MCP-1 levels were significantly (P < .001) higher than group B and exhibited a positive correlation with HbA1c (P < .001) and a negative correlation with ankle-brachial index (P < .001). In the same group, patients with PAD had significantly higher MCP-1 levels compared with those without PAD (P < .001). In conclusion, T2DM patients with MetS exhibit higher serum MCP-1 levels. The latter is associated with worse glycemic control and PAD. These results suggest a potential contributory role for MCP-1 in the pathogenesis of PAD in the presence of hyperglycemia and MetS in T2DM.

In vivo measurement of radius calcium/phosphorus ratio by X-ray absorptiometry.

We describe a new method for assessing the skeletal Ca/P ratio in vivo using X-ray absorptiometry. By placing cerium (Ce) and samarium (Sm) filters in the X-ray beam from a commercial X-ray source (Norland), mean photon energies of 39 and 89 keV were obtained. The instrument was designed to take measurements of the forearm, at a site located at the distal 1/3 of the radius. The system was calibrated with three bone phantoms: Ca10(PO4)6(OH)2, Ca(HPO4)(H2O)2 and Ca(HPO4)2(H2O)). The precision for measuring the Ca/P ratio in the human radius was 2.3% CV for a skin dose to the forearm ranging from 0.3 to 0.4 mGy, depending on the width of the arm. The Ca/P ratio of the radius was significantly lower in patients with postmenopausal osteoporosis than in premenopausal controls.

The effects of inflammation-mediated osteoporosis (IMO) on the skeletal Ca/P ratio and on the structure of rabbit bone and skin collagen.

The relationships between the skeletal Ca/P ratio (used as an index of bone quality) and structural changes in the bone and skin was studied in inflammatory mediated osteoporosis (IMO). The bone Ca/P ratio in IMO rabbits was significantly lower than in controls. Also, severe alterations were detected at the ultrastructural level in bone and skin collagen fibrils from IMO rabbits.

The skeletal calcium/phosphorus ratio: a new in vivo method of determination.

We describe a new method for assessing the Ca/P ratio of bone in vivo using gamma-ray photon absorptiometry. The theoretical approach of the method and the estimation of the variance are presented. Two radiation sources, Gd-153 (100 keV), and I-125 (27.5 keV), and a germanium detector were used to determine this ratio. Measurements were made on bone phantoms with different Ca/P ratios; also, the ratio was measured on lamb and sheep tibias, rabbit tibias, and human fingers. Since the accuracy of the method is affected by the amount of fat and collagen in the measurement field, the effect of collagen and fat on the measurements also was investigated. In all cases, the precision of the method, expressed as the coefficient of variation (CV): 100x standard deviation/mean, was near to the theoretical one, ranging from 1.8% to 3.2%. For human fingers, the CV was 3.2%, a value near to the theoretical 2.9% with a dose to the skin ranging from 0.044 to 0.066 mGy, depending on the width of the finger.

Influence of low doses of gamma-irradiation on mouse skin collagen fibrils.

The structure of mouse skin collagen fibrils after treatment with 0.5, 1 and 2.5 Gy gamma-irradiation was studied by electron microscopy. Animals were sacrificed 1, 4 and 8 weeks after irradiation. Although there were areas where the normal parallel packing of fibrils was retained in some regions packing was interrupted by abnormal fibrils and in some cases helical twisting was apparent. Irradiated collagen fibrils had a lower mean diameter compared with normal and a large variability in width. The diameter of 0.5 Gy irradiated fibrils returned to normal by 4 or 8 weeks after irradiation. Clusters of abnormal fibrils were found when viewed in cross-sections. Their number and size was reversibly dependent on the dose level. All fibrils retained normal banding periodicity. Computer analysis of irradiated and control patterns led to the conclusion that 0.5-2.5 Gy gamma-irradiation had no considerable effect in modifying the charge distribution along the mouse skin collagen fibril.

Elemental composition of bone minerals in women with breast cancer treated with adjuvant tamoxifen.

Oestrogen levels play a major role in conditioning the rates of bone changes in women. Tamoxifen is a synthetic oestrogen antagonist commonly used as an adjuvant therapy for breast cancer. The goal of the present study was to study the amount and the elemental composition of bone minerals in the appedicular skeleton of women with breast cancer treated with adjuvant tamoxifen, as well as to investigate the possibility of increased risk for osteoporosis. Forty-two patients, aged 41-65 years, without skeletal metastases were studied. The mean duration of tamoxifen administration on a daily dose of 20 mg was 21 months (range 1-59 months). It was found that neither the amount of phosphorus in hands (HBP) nor forearm bone mineral content (BMC) differ statistically from those of age-matched healthy subjects. This was confirmed by reassessing bone mineral status after 30 months in 17 postmenopausal patients treated with tamoxifen for a mean time of 52 months. In conclusion, our data support that long-term tamoxifen treatment has no adverse or protective effect on the amount and elemental composition of the appedicular skeleton.

Bone minerals in beta-thalassemia minor.

Homozygous beta-thalassemia is a severe hereditary disorder associated with osteopenia. Recently it was suggested that thalassemia minor may be a risk factor for osteoporosis. The purpose of the present study was to investigate this suggestion. Bone mineral status was assessed in 22 premenopausal women and 21 men with beta-thalassemia minor. In vivo neutron activation analysis was applied to measure hand-bone phosphorus (HBP), single-photon absorptiometry to measure forearm bone mineral content (BMC), and dual-energy X-ray absorptiometry to measure spinal bone mineral density (BMD). Comparison of the HBP, BMC, and BMD values with those of sex- and age-matched healthy subjects without the beta-thalassemia trait failed to indicate a statistically significant difference for either sex group. Concerning the biochemical markers of bone metabolism that were studied (serum calcium, phosphate, alkaline phosphatase, osteocalcin, and parathyroid hormone, and 3-h fasting urine calcium-to-urine creatinine ratio) no difference was observed between the study subjects and matched controls. In conclusion, the present study showed that subjects with beta-thalassemia minor are not at risk for osteoporosis.

An electron microscopic study of collagen fibril structure after lithium treatment--II. The effects of low lithium dose and short treatment on mouse skin collagen.

The structure of mouse skin collagen fibrils, after treatment with lithium chloride at a dose of 0.7 meq/kg of body weight, was studied by electron microscopy. Animals were sacrificed 1-day, 1-, 2- and 6-months after the end of 30 consecutive days experimental period. Fibrils in disarray interspersed with normal ones were seen, although there were areas where the normal parallel packing of fibrils was completely replaced by a random arrangement. In some regions this packing was interrupted by fibrils forming a 'hairpin loop' and in some others helical twisting was apparent. Lithium treated collagen fibrils had a marked decrease in mean diameter compared to normal with a high variability in width. Clusters of abnormal fibrils were found when viewed in cross-sections, constituted approximately 10% of the whole population with an irregular outline. A shorter experimental period (7 days) leads to the same features in collagen disorganization as with the longer experimental period (30 periods). However, in short lithium treatment, there is no high variability in fibril width and although fibrils are smaller than the control, the decrease in mean diameter is not so pronounced as with longer treatment. In general, fibril diameter becomes altered progressively with experimental time. Lower dose, 0.3 meq Li/kg, in short treatment (7 days), leads to a normal collagen organization although in some areas fibril twisting is observed. Fibril diameter is not considerably affected.

Bone mineral status after renal transplantation. Assessment by noninvasive techniques.

RATIONALE AND OBJECTIVES: Bone mineral status in recipients of renal grafts is related to preexisting renal osteodystrophy and immunosuppressive treatment. The authors assessed bone mineral status after renal transplantation. METHODS: Bone mineral status of 20 male graft recipients was evaluated using the following noninvasive techniques: 1) neutron activation analysis, to measure hand bone phosphorus (HBP); 2) single photon absorptiometry, to measure forearm bone mineral content (BMC); and 3) single energy spectrum quantitative computed tomography, to measure spinal trabecular bone equivalent density (TBED). RESULTS: The mean (+/- SD, P) HBP, BMC, and TBED were found to be respectively, 4.8% (+/- 8.3%, P = .02), 6.6% (+/- 14.6%, P = .07) and 52% (+/- 8.5%, P < .001) lower than that measured in matched normal controls. Renal graft recipients demonstrated mean HBP and BMC decrements that were similar to those observed in matched patients on extrarenal dialysis, although the decrement in TBED was significantly greater in the graft recipients (P < .001). Repeated measurements performed during a 3-year period showed no statistically significant changes. CONCLUSIONS: Renal transplantation was associated with minor degree of osteopenia in the primarily cortical bone tissue. We speculate that the remarkably low TBED values in graft recipients does not reflect a mean 52% decrement of spinal bone minerals, but rather may be attributed in part to the deposition of adipose tissue in the spine as a result of corticosteroid treatment.

An electron microscopic study of collagen fibril structure after lithium treatment--I. The effect of different lithium doses on mouse skin collagen.

The structure of mouse skin collagen fibrils after treatment with lithium chloride at doses of 1.5 and 6 meq/kg of body weight was studied by electron microscopy. Animals were sacrificed 1 day, 1, 2 and 6 months after the end of a 30 consecutive days experimental period. With the first dose, which is commonly used clinically, although there were areas with normal collagen fibrils there were also regions where the characteristic parallel packing of fibrils was lost completely or it was preserved for a part of the area. With high doses, in most regions the normal packing of fibrils was replaced by an anarchic arrangement. In both cases, collagen fibrils had a marked decrease in mean diameter and showed a higher degree of variability in width and shape than collagen fibrils from controls. Also, many clusters of abnormal fibrils were found with a diameter of up to 260 nm vs 109 nm and a highly irregular outline when viewed in cross-sections. The periodicity D as well as the banding pattern were normal.

In vivo animal models of body composition in aging.

We developed several techniques that provide data on body elemental composition from in vivo measurements in rats. These methods include total body potassium by whole-body counting of endogenous 40K; total body calcium (TBCa), sodium and chloride by in vivo neutron activation analysis and total body phosphorus (TBP) and nitrogen (TBN) by photon activation analysis. These elements provide information on total body fat, total body protein and skeletal mass. Measurements were made in 6-, 12- and 24-month-old rats. TBN increased slightly between 6 and 12 months but was significantly lower by 24 months, indicating a substantial loss in total body protein. Working at the National Synchrotron Light Source, we studied rat femurs by computed microtomography (CMT), and the elemental profile of the femur cortex by synchrotron-radiation induced X-ray emission (SRIXE). Although there were no significant changes in TBCa and TBP, indices of skeletal mass, CMT revealed a marked increase in the size and number of cavities in the endosteal region of the femur cortex with increasing age. The SRIXE analysis of this cortical bone revealed a parallel decrease in the endosteal Ca/P ratio. Thus, there are major alterations in bone morphology and regional elemental composition despite only modest changes in total skeletal mass.

New evidence that tamoxifen does not induce osteoporosis: a nuclear activation analysis and absorptiometry study.

The possibility of increased risk for osteoporosis in breast cancer patients treated with tamoxifen was investigated. 26 patients aged 41-65 years without skeletal metastases were studied. All patients were treated with 20 mg/d tamoxifen for a mean time of 22 months. The data obtained by in vivo neutron activation analysis of the phosphorus content in hands, were supplemented with data obtained by single photon absorptiometry in the forearm and radiographic morphometry. Comparison of the data with that of age and sex matched normal controls showed that breast cancer patients treated with tamoxifen are not prone to osteoporosis.

Limitations of quantitative CT in corticosteroid induced osteopenia.

Single energy spectrum quantitative CT (SES-QCT) was applied for the assessment of the trabecular bone mineral status in patients under long-term corticosteroid treatment. Seventeen renal graft recipients (RGR) and 12 patients receiving corticosteroid treatment for collagen disease were studied. A reduction of about 40% in the spinal trabecular bone density relative to matched controls was found, associated with the corticosteroid administration. Repeated measurements showed significant reduction in density 4 months after transplantation, and an increase in density after graft rejection. Radiologic or clinical evidence of osteopenia in the spine was not found. Other noninvasive techniques, applied in the upper extremities of the RGR, showed only minor bone reduction compared to controls. The findings of the present study suggest that adipose tissue deposition in the spinal trabeculae can introduce errors in the measurements. Therefore, SES-QCT should not be applied during corticosteroid therapy.

Quantitative computed tomography for bone mineral measurement: technical aspects, dosimetry, normal data and clinical applications.

A single KVp quantitative CT (QCT) technique was used for measuring the spinal trabecular bone density. The trabecular bone equivalent density (TBED) was expressed as the density of a K2HPO4 solution that exhibits a linear attenuation coefficient identical to that of trabecular bone. A field non-uniformity correcting factor was obtained from experiments on phantoms. The effective equivalent dose of the whole examination (four sections and a scout view) is 370 muSv. The in vivo short-term precision (reproducibility coefficient of variation) ranges from 1.4% to 4.1% depending on the TBED values of the normal subjects. The TBED was measured in 206 normal Greeks aged 30-69 years. Average TBED decreased with increasing age for both sexes. Analysis considering separately each vertebra showed a tendency to a caudal spinal TBED reduction. No correlation was found between the TBED values and the body habitus, milk consumption, smoking habits in men, and number of full-term pregnancies. A significant difference (p less than 0.01) was found between the TBED values of the normals and those of 50 women suffering from post-menopausal osteoporosis, 37 alcoholic men, and 12 gastrectomized men (Billroth II). Quantitative CT has been established as a method of measuring TBED in health and disease, and the results from this study confirm these applications.

Streptococcus sanguis survival in K-Sol. Comparison of gentamicin and the fluoroquinolone antibiotics.

Viridans streptococci are poorly covered by gentamicin sulfate in corneal storage medium. To evaluate possible antibiotic alternatives among the newer broad-spectrum fluoroquinolone antibiotics, we compared the survival of the viridans representative Streptococcus sanguis in K-Sol with gentamicin sulfate (100 mg/L), norfloxacin (250 mg/L), ciprofloxacin lactate (250 mg/L), ofloxacin (250 mg/L), or no antibiotic. At 23 degrees C, K-Sol with gentamicin produced a 2-log kill by 80 minutes. By comparison, only one of the others (norfloxacin) had achieved a 2-log kill by 4 hours. At 4 degrees C, all antibiotics differed little from the control, and none was superior to gentamicin.

Effects of epikeratoplasty on the host cornea. An experimental study.

The effects of epikeratoplasty on the host cornea was studied using albino rabbits. Eyes underwent midperipheral partial trephination alone (group I), midperipheral partial trephination and peripheral undermining (group II), midperipheral partial trephination and circular keratectomy (group III), and trephination, peripheral undermining, and circular keratectomy (group IV). Corneal topography was assessed weekly using keratometry and photokeratoscopy. All eyes showed central corneal steepening with enhancing effects of increased surgical manipulation. Results were stable by 4 weeks in all eyes. Histopathologic evaluation revealed a constant wound depth of approximately 0.1 mm, with an increased accumulation of glycosaminoglycan material at the base of the wound. This was stained with PAS and alcian blue. Steepening of the host cornea may be another reason for lack of predictability and refractive regression following epikeratoplasty.