Correlates of T50 and relationships with bone mineral density in community-living older men: the osteoporotic fractures in men (MrOS) study.

PURPOSE: T50 is a novel serum-based marker that assesses the propensity of calcification in serum. Shorter T50 indicates greater propensity to calcify and it has been associated to cardiovascular disease (CVD) and mortality among patients with kidney disease. In the general population, neither the correlates of T50 nor the relationships of T50 with bone mineral density (BMD) are known. METHODS: We performed a nested cross-sectional study selecting 150 individuals at random among participants from the Osteoporotic Fractures in Men (MrOS) Study, a study of community-living older men. We categorized individuals into tertiles of T50 and compared demographics and disease indicators across tertiles. We utilized linear regression to evaluate the cross-sectional association between T50 and hip and spine BMD in multivariable models. RESULTS: Older age was associated with shorter T50. Kidney function tended to be lower in those with shorter T50 and the prevalence of CVD and peripheral arterial disease in those with shorter T50, albeit these findings did not achieve statistical significance. We found no statistically significant associations between T50 and total hip or total spine BMD in either unadjusted or multivariable adjusted models. CONCLUSIONS: T50, a novel indicator of serum calcification propensity, is not associated with BMD in community-living older men. Future larger studies should determine if T50 may give insights to CVD in the general population above and beyond traditional risk factors.

Acute and 3-month effects of calcium carbonate on the calcification propensity of serum and regulators of vascular calcification: secondary analysis of a randomized controlled trial.

SUMMARY: Calcium supplements have been associated with increased cardiovascular risk, but the mechanism is unknown. We investigated the effects of calcium supplements on the propensity of serum to calcify, based on the transition time of primary to secondary calciprotein particles (T50). Changes in serum calcium were related to changes in T50. INTRODUCTION: Calcium supplements have been associated with increased cardiovascular risk; however, it is unknown whether this is related to an increase in vascular calcification. METHODS: We investigated the acute and 3-month effects of calcium supplements on the propensity of serum to calcify, based on the transition time of primary to secondary calciprotein particles (T50), and on three possible regulators of calcification: fetuin-A, pyrophosphate and fibroblast growth factor-23 (FGF23). We randomized 41 postmenopausal women to 1 g/day of calcium as carbonate, or to a placebo containing no calcium. Measurements were performed at baseline and then 4 and 8 h after their first dose, and after 3 months of supplementation. Fetuin-A, pyrophosphate and FGF23 were measured in the first 10 participants allocated to calcium carbonate and placebo who completed the study. RESULTS: T50 declined in both groups, the changes tending to be greater in the calcium group. Pyrophosphate declined from baseline in the placebo group at 4 h and was different from the calcium group at this time point (p = 0.04). There were no other significant between-groups differences. The changes in serum total calcium from baseline were significantly related to changes in T50 at 4 h (r = -0.32, p = 0.05) and 8 h (r = -0.39, p = 0.01), to fetuin-A at 3 months (r = 0.57, p = 0.01) and to pyrophosphate at 4 h (r = 0.61, p = 0.02). CONCLUSIONS: These correlative findings suggest that serum calcium concentrations modulate the propensity of serum to calcify (T50), and possibly produce counter-regulatory changes in pyrophosphate and fetuin-A. This provides a possible mechanism by which calcium supplements might influence vascular calcification.

Serum Calcification Propensity Is a Strong and Independent Determinant of Cardiac and All-Cause Mortality in Kidney Transplant Recipients.

Calcification of the vasculature is associated with cardiovascular disease and death in kidney transplant recipients. A novel functional blood test measures calcification propensity by quantifying the transformation time (T50 ) from primary to secondary calciprotein particles. Accelerated T50 indicates a diminished ability of serum to resist calcification. We measured T50 in 1435 patients 10 weeks after kidney transplantation during 2000-2003 (first era) and 2009-2012 (second era). Aortic pulse wave velocity (APWV) was measured at week 10 and after 1 year in 589 patients from the second era. Accelerated T50 was associated with diabetes, deceased donor, first transplant, rejection, stronger immunosuppression, first era, higher serum phosphate and lower albumin. T50 was not associated with progression of APWV. During a median follow-up of 5.1 years, 283 patients died, 70 from myocardial infarction, cardiac failure or sudden death. In Cox regression models, accelerated T50 was strongly and independently associated with both all-cause and cardiac mortality, low versus high T50 quartile: hazard ratio 1.60 (95% confidence interval [CI] 1.00-2.57), ptrend = 0.03, and 3.60 (95% CI 1.10-11.83), ptrend = 0.02, respectively. In conclusion, calcification propensity (T50 ) was strongly associated with all-cause and cardiac mortality of kidney transplant recipients, potentially via a cardiac nonAPWV-related pathway. Whether therapeutic improvement of T50 improves outcome awaits clarification in a randomized trial.

Exogenous administration of thiosulfate, a donor of hydrogen sulfide, attenuates angiotensin II-induced hypertensive heart disease in rats.

BACKGROUND AND PURPOSE: Hypertension is an important mediator of cardiac damage and remodelling. Hydrogen sulfide (H2S) is an endogenously produced gasotransmitter with cardioprotective properties. However, it is not yet in clinical use. We, therefore, investigated the protective effects of sodium thiosulfate (STS), a clinically applicable H2 S donor substance, in angiotensin II (Ang II)-induced hypertensive cardiac disease in rats. EXPERIMENTAL APPROACH: Male Sprague Dawley rats were infused with Ang II (435 ng kg min(-1)) or saline (control) for 3 weeks via s.c. placed osmotic minipumps. During these 3 weeks, rats received i.p. injections of either STS, NaHS or vehicle (0.9% NaCl). KEY RESULTS: Compared with controls, Ang II infusion caused an increase in systolic and diastolic BP with associated cardiac damage as evidenced by cardiac hypertrophy, an increase in atrial natriuretic peptide (ANP) mRNA, cardiac fibrosis and increased oxidative stress. Treatment with NaHS and STS prevented the development of hypertension and the increase in ANP mRNA levels. Furthermore, the degree of cardiac hypertrophy, the extent of histological fibrosis in combination with the expression of profibrotic genes and the levels of oxidative stress were all significantly decreased. CONCLUSIONS AND IMPLICATIONS: Ang II-induced hypertensive cardiac disease can be attenuated by treatment with STS and NaHS. Although BP regulation is the most plausible mechanism of cardiac protection, the antifibrotic and antioxidant properties of released sulfide may also contribute to their effects. Our data show that H2 S might be a valuable addition to the already existing antihypertensive and cardioprotective therapies.

Impact of proton pump inhibitor use on magnesium homoeostasis: a cross-sectional study in a tertiary emergency department.

BACKGROUND: To date, the use of proton pump inhibitors (PPIs) has been associated with a low risk of hypomagnesaemia and associated adverse outcomes. We hypothesised that a better risk estimate could be derived from a large cohort of outpatients admitted to a tertiary emergency department (ED). METHODS: A cross-sectional study was performed in 5118 patients who had measurements of serum magnesium taken on admission to a large tertiary care ED between January 2009 and December 2010. Hypomagnesaemia was defined as a serum magnesium concentration < 0.75 mmol/l. Demographical data, serum electrolyte values, data on medication, comorbidities and outcome with regard to length of hospital stay and mortality were analysed. RESULTS: Serum magnesium was normally distributed where upon 1246 patients (24%) were hypomagnesaemic. These patients had a higher prevalence of out-of-hospital PPI use and diuretic use when compared with patients with magnesium levels > 0.75 mmol/l (both p < 0.0001). In multivariable regression analyses adjusted for PPIs, diuretics, renal function and the Charlson comorbidity index score, the association between use of PPIs and risk for hypomagnesaemia remained significant (OR = 2.1; 95% CI: 1.54-2.85). While mortality was not directly related to low magnesium levels (p = 0.67), the length of hospitalisation was prolonged in these patients even after adjustment for underlying comorbid conditions (p < 0.0001). CONCLUSION: Use of PPIs predisposes patients to hypomagnesaemia and such to prolonged hospitalisation irrespective of the underlying morbidity, posing a critical concern.

A two-staged technique for basilic vein transposition.

The dilemma of creating a fistula in patients without a use-able cephalic vein can be addressed by basilic vein transposition, yet results of the classic single-stage procedure are inconsistent and surgeon utilization of this procedure is variable. This article describes a two-staged technique for basilic vein transposition. The two-staged technique is likely to facilitate higher fistula rates in patients unable to have a direct fistula, and warrants consideration by surgeons striving to achieve higher fistula rates.

[Metaphylaxis of recurrent renal calcium stones]. / Wie vermeidet man kalziumhaltige Nierensteine?

Calcium containing renal stones represent a common medical problem and show a high rate of recurrence. Therefore, besides the treatment of acute stone episodes, also the prevention of new stone episodes is of crucial importance in the medical care of stone formers. To avoid stone recurrences, medical as well as dietary measures should be established based on the results of a thorough evaluation and the elaboration of an individual risk profile. This review article describes and discusses the currently established treatment options for the prophylaxis of calcium-containing renal stones.

[Urine analyses for workup of kidney stone disease--interpretation and therapeutic consequences]. / Urindiagnostik bei Nephrolithiasis--Interpretation und therapeutische Konsequenzen.

Nephrolithiasis is a disease with a high and even rising incidence. It has a high morbidity, generates high costs and has a high recurrence rate. Urinalysis is of importance especially in recurrent stone formers. It allows the identification and quantification of risk factors and the establishment of individual risk profiles. Based on these individual risk profiles, rational therapy for metaphylaxis of kidney stones lowers stone recurrence rates significantly. This review article aims to give a focussed overview of the most important risk factors for kidney stones and reasonable urine tests for evaluation of recurrent kidney stone formers.

Comparative analysis of two coxsackievirus B3 strains: putative influence of virus-receptor interactions on pathogenesis.

Strain-specific differences in the interaction of coxsackievirus B3 (CVB3) with the coxsackievirus-adenovirus receptor (CAR) and the decay-accelerating factor (DAF) co-receptor proteins were investigated using a non-haemagglutinating (CVB3) and a haemagglutinating (CVB3-HA) strain of CVB3. A panel of receptor-transfected hamster CHO cells, expressing either CAR (CHOCAR cells), DAF (CHODAF cells), or both receptor proteins (CHODC cells) were used to study the interplay of CAR and DAF receptor molecules with regard to binding and infection with CVB3 and CVB3-HA. Despite clear differences in their binding phenotypes, both virus strains were found to primarily depend on the CAR receptor protein for initialization of productive infections. Cytopathic effects induced by CVB3-HA were influenced by co-expression of DAF receptor proteins. The cardiotropic potential of both virus strains was investigated in A.BY/SnJ mice. Despite comparable virus replication of both CVB3 strains in individual myocytes, the number of infected heart muscle cells was significantly lower in CVB3-HA infected mice. Infections of pancreata correlated with myocardial infections. Together these data suggest that even small differences in virus-receptor interactions, influencing virus binding and virus spread, may have an impact on the pathogenesis of CVB-induced diseases.

Coxsackie B virus and its interaction with permissive host cells.

BACKGROUND: Observations in humans and the results of experiments on laboratory animals have provided evidence that coxsackieviruses of group B (CVB) are major etiologic agents of acute and chronic enterovirus myocarditis and various other virus-induced diseases. OBJECTIVE: This minireview briefly summarizes the investigations to elucidate various molecular mechanisms for the induction and maintenance of persistent CVB infections. With regard to the recent findings that CVB may use several different receptor proteins, this article focuses on virus-host cell interactions and the potential impact of these interactions for enteroviral replication. STUDY DESIGN: The interaction of CVB with specific cell surface proteins was analyzed in cultured cell lines and murine tissues at the level of virus attachment and virus internalization. As example for the interaction of CVB with intracellular proteins, the state of p21rasGTPase-activating protein (RasGAP) was investigated in mock-infected and CVB3-infected HeLa cells. RESULTS AND CONCLUSIONS: The experiments to elucidate the virus receptor interactions revealed the necessity to differentiate between CVB attachment proteins and proteins involved in virus internalization. Since more than one protein may be required to initiate the uptake of CVB into permissive host cells, a model of the putative interaction of these proteins within a multimeric receptor complex is proposed. It is further tempting to speculate that the presence of multiple attachment proteins may influence the tissue tropism of CVB as well as pathogenicity.

The necessity of mandatory exploration of penetrating zone II neck injuries.

To reevaluate the validity of our policy of mandatory surgical exploration of penetrating zone II neck injuries, the charts of 110 patients who underwent surgical exploration for such injuries were reviewed. Fifty-three percent of the patients had normal findings at exploration, whereas 33% had injuries involving vascular structures of the neck and 14% had nonvascular injuries. Injuries were not suspected on clinical grounds preoperatively in 23% of the patients in whom surgical exploration revealed injury. The injuries most likely to escape preoperative diagnosis were isolated venous injuries and isolated pharyngoesophageal injuries. Arteriography yielded false-negative results in two arterial injuries. No deaths and only a 5% incidence of minor complications occurred in the group with no injuries detected at exploration. We conclude that surgical exploration of penetrating zone II neck injuries is safe and appropriate.

Efficacy of femorofemoral bypass for intermittent claudication. Clinical and hemodynamic assessment.

Twenty patients treated by femorofemoral bypass were retrospectively reviewed to determine if femorofemoral bypass was efficacious in the treatment of disabling claudication. The data have clearly demonstrated that two criteria are necessary for the successful outcome of femorofemoral bypass. First, the donor artery should be hemodynamically normal in order to support the recipient limb. This can be determined by either a normal treadmill exercise test result or by a normal preoperative intraarterial papaverine test result. Second, the patient's functional improvement will be dependent on the status of the runoff vessels in the recipient limb; therefore, many patients with patent superficial femoral and popliteal arteries will have excellent results (50 percent in this series), whereas those with occluded superficial femoral or popliteal arteries or both will have less improvement (40 percent in this series). Therefore, femorofemoral bypass should be used in the treatment of intermittent disabling claudication in the properly selected patient.

Results of arterial reconstruction of the foot.

Sixty-five patients with critical ischemia required bypass to foot vessels. These procedures were performed by five different techniques: (1) femoral-foot bypass with in situ saphenous vein; (2) femoral-foot bypass with reversed autogenous saphenous vein; (3) femoral-foot bypass with polytetrafluoroethylene (PTFE); (4) popliteal-foot bypass with reversed autogenous saphenous vein; and (5) popliteal-foot bypass with PTFE. The two-year patency rate of femoral-foot bypass with in situ vein (96%) was significantly higher than femoral-foot bypass with reversed vein (42%), while both procedures demonstrated significantly higher patency than femoral-foot bypass with PTFE (0%). Popliteal-foot bypass with reversed vein (92%) was superior to both popliteal-foot bypass with PTFE (27%) and femoral-foot bypass with PTFE (0%). Femoral-foot bypass with in situ vein and popliteal-foot bypass with reversed vein have appreciably increased vein utilization, graft patency, and limb salvage.

Improved results in the treatment of civilian vascular injuries associated with fractures and dislocations.

Patients with vascular injuries associated with fractures or dislocations of the extremities were managed according to a standard protocol, which included the liberal use of preoperative arteriography, early fasciotomy when indicated, individualization of timing and type of orthopedic procedures, arterial reconstruction primarily with interposition reversed saphenous vein grafts, repair of major venous injuries, routine completion arteriography, and regular postoperative monitoring of Doppler-derived ankle/brachial indices. Adherence to these principles led to a limb salvage rate of 97% in 38 patients with such injuries.

Results of venous reconstruction after civilian vascular trauma.

The treatment of venous injuries remains controversial. In an attempt to evaluate the results of current management of venous injuries, we retrospectively reviewed our experience between 1979 and 1984. During this period 142 patients had sustained injuries to 158 veins in the neck (31 patients), abdomen (45 patients), upper extremity (20 patients), and lower extremity (62 patients). Overall, 90 venous injuries (61%) were repaired, including 83% of caval and iliac vein injuries and 90% of injuries to the common femoral, superficial femoral, and popliteal veins. There was no morbidity after repair of 73 major veins. Morbidity occurred in four of 11 patients after ligation of major veins (edema in two patients and above-knee amputation in two others). Both ligation (N = 51) and repair (N = 17) of lesser veins (jugular, brachial, profunda femoral, tibial, and minor abdominal veins) resulted in no morbidity. Overall mortality was 6% with all deaths occurring in patients with abdominal venous trauma. These data indicate that repair of venous injuries can be performed without morbidity and that minor veins can be ligated without adverse sequelae. However, in view of the morbidity associated with ligation of major veins, efforts to restore flow to these injured vessels appear appropriate unless contraindicated by life-threatening injury.

Optimal limb salvage in penetrating civilian vascular trauma.

To evaluate current treatment of peripheral vascular trauma, we reviewed our recent experience with noniatrogenic penetrating vascular injuries of the extremities. Between 1979 and 1984, 139 patients sustained 204 vascular injuries inflicted by single gunshots (64%), stabbings (24%), and shotguns (12%). Eighty-four percent of patients underwent preoperative arteriography, which revealed occult arterial injury in 13 patients (9%). Compartmental hypertension necessitated fasciotomy in 19% of patients and was required more often after combined arterial and venous injuries (29%) than after isolated arterial injury (14%). Arterial continuity was restored by interposition grafting with reversed saphenous vein (62%), end-to-end anastomosis (19%), vein patch angioplasty (8%), or primary repair (4%). After arterial repair, completion angiography detected the need for revision in 8% of patients. Arterial ligation was performed in 7% of injuries and was only used in the treatment of tibial and distal profunda femoris injuries. Forty-five percent of patients sustained concomitant venous injury; 64% of all venous injuries and 90% of femoropopliteal venous injuries were repaired. No deaths occurred, and a single patient required amputation. We conclude that a protocol of preoperative arteriography, liberal. use of fasciotomy, frequent use of autologous interposition grafts, repair of major venous injuries, and routine use of completion arteriography can result in limb salvage rates that approach 100% after penetrating vascular trauma to the extremities.

Subclavian steal despite ipsilateral vertebral occlusion.

In the classic subclavian steal syndrome, vertebrobasilar insufficiency is caused by reverse flow in the vertebral artery ipsilateral to a subclavian stenosis or occlusion. We present two patients with vertebrobasilar insufficiency and ipsilateral vertebral and subclavian occlusive disease. The postulated mechanism of vertebrobasilar insufficiency is reverse flow in collateral neck vessels. In both patients, symptoms were relieved by carotid subclavian bypass. Thus, vertebral occlusion ipsilateral to a subclavian stenosis does not preclude subclavian steal syndrome.

Ankle bypass: should we go the distance?

This report reviewed the results of 47 distal arterial reconstructions to or below the level of the malleolus. The operations were performed by the techniques of popliteal-to-distal bypass (20 procedures) and in situ bypass (27 procedures). Seventy-five percent of patients had gangrene of ischemic ulceration, and all procedures were performed for limb salvage. Seventy-three percent of all patients were diabetic. The patency rates for popliteal-to-distal bypass with reversed saphenous vein were 92 percent at 24 months and 57 percent at 60 months, with a limb salvage rate of 70 percent at 60 months; the patency rates for popliteal-to-distal bypass with PTFE were 53 percent at 12 months and 0 at 36 months, with a limb salvage rate of 53 percent at 36 months; and the patency rate for in situ saphenous vein bypass was 96 percent at 24 months, with a limb salvage rate of 80 percent at 24 months. Early results are promising for ankle bypass using the techniques of popliteal-to-distal and in situ bypass.

Jejunal interposition for recurrent gastroesophageal reflux in children.

There is limited experience with surgical treatment for recurrent gastroesophageal reflux after an antireflux procedure. In four pediatric patients with recurrent reflux after surgical therapy, interposition of an isoperistaltic segment of jejunum produced excellent short-term results. Further follow-up is needed as experience broadens. At the present time, this procedure merits consideration in patients with recurrent gastroesophageal reflux.

Abdominal aortic aneurysm: the case for elective resection.

Abdominal aortic aneurysms are one of the more common problems faced by the vascular surgeon. A review of 898 aneurysms resected at the University of Rochester from 1955 to 1982 revealed a sequential decrease in mortality for elective surgery from 13% in 1955 to 1965, to 8.4% from 1966 to 1973, and 5.6% in the last 8 years. Mortality for resection of ruptured aneurysms remained high (70%). The incidence of ruptured aneurysms has not changed significantly in the last 16 years. For 1980 and 1981 we calculated the hospital costs of surgical treatment of abdominal aortic aneurysms. The mean total cost after elective resection was +10,114 compared with +18,223 after rupture. Increased costs after rupture reflected both a longer stay and more intensive and expensive medical care. Using discharge data from U.S. hospitals in 1979, we extrapolated our cost and mortality data to a national level. Assuming a mortality rate for elective resection of 5% and a mortality rate for resection after rupture of 50%, we estimated that in 1979 +50 million and over 2000 lives could have been saved if patients with abdominal aortic aneurysms had been identified and subjected to elective resection. The incidence of ruptured abdominal aortic aneurysms remains unacceptably high. Mortality from this disease can best be reduced by increased physician awareness and prompt surgical referral.(ABSTRACT TRUNCATED AT 250 WORDS)