The effect of thiazide and loop diuretics on urinary levels of free deoxypyridinoline: an osteoclastic bone-resorption marker.

WHAT IS KNOWN AND OBJECTIVE: Diuretics can cause changes in calcium levels due to renal effects. Moreover, calcium levels can also vary as a result of changes in intestinal absorption and in the activity of osteoclastic cells. A marker of osteoclastic bone-resorption activity is the level of urinary free deoxypyridinoline (FDP). Deoxypyridinoline (DP) acts as a cross-link between adjacent collagen chains to provide structural rigidity. Our aim was to investigate the association between use of thiazides and loop diuretics and urinary levels FDP. METHODS: In this follow-up study, data were obtained from the Rotterdam Study, a large population-based prospective cohort study. For a subset of 658 participants, urinary levels of FDP were measured at baseline. Linear regression analysis was performed to assess the association between the use of thiazides and loop diuretics and the urinary levels of FDP. RESULTS: In women, current use of loop diuretics for less than 42 days was associated with an increased level of urinary FDP (+3·43 nmol deoxypyridinoline per mmol urinary creatinine; 95% CI 1·85; 5·02) compared with no use. However, use for a period of more than 42 days was not associated with an increased level of FDP, nor was past use of loop diuretics. For thiazide diuretics, no statistically significant associations were found. WHAT IS NEW AND CONCLUSION: In women, short-term use of loop diuretics is associated with an increased level of FDP, reflecting increased bone resorption by osteoclasts. As the difference disappears with longer term use, the clinical significance is unclear and the value of FDP as a biomarker in this setting is not established. The molecular mechanism for the observed differences in bone fracture rates with use of diuretics remains unclear.

Out of hospital treatment of acute pulmonary embolism in patients with a low NT-proBNP level.

BACKGROUND: Low NT-proBNP levels are associated with an uncomplicated course in patients with pulmonary embolism (PE). The aim of this multicenter management study was to investigate the safety of home treatment of patients with PE with low (< 500 pg mL(-1)) NT-proBNP. METHODS AND RESULTS: Hemodynamically stable outpatients with acute PE and NT-proBNP level < 500 pg mL(-1) were included. Patients were discharged immediately from the emergency room or within a maximum of 24 h after admission. The primary study objective was the absence of mortality during the first 10 days of treatment. Secondary objectives were the incidence of re-admission due to PE or its treatment and the patient's satisfaction during the first 10 days of treatment as well as the incidence of serious adverse events during the 3-month follow-up period. Of 351 patients, 152 (43%) fulfilled the inclusion criteria and were treated as outpatients. No deaths, major bleedings or recurrent venous thromboembolism occurred in the first 10 days of treatment or in the follow-up period of 3 months in these patients. Seven patients required readmission in the first 10 days: three because of complaints that could be related to PE and four due to an illness unrelated to PE. The HADS-A anxiety score did not change significantly between day 0 and day 10. The PSQ-18 showed a high score for satisfaction with home treatment. CONCLUSION: Out of hospital treatment is safe in hemodynamically stable patients with PE with low (< 500 pg mL(-1)) NT-proBNP levels. Approximately 45% of patients with PE can be treated in an outpatient setting. Patients do not consider out of hospital treatment as inconvenient and have no increase in anxiety scores. CLINICAL TRIAL REGISTRATION INFORMATION: http://clinicaltrials.gov/ct2/show/NCT00455819.

Improved cardiovascular risk profile in patients referred to a specialised vascular outpatient clinic: a cohort study.

We carried out a prospective cohort study in patients referred to our vascular outpatient clinic to see how their cardiovascular risk profile developed. The classical risk factors were compared at first visit and one year later. The adapted Framingham Heart Risk Score (FHRS) and the Heart SCORE (HS) were used to compare the cardiovascular risks. There was a decline of 9 and 5 mmHg in mean systolic blood pressure in the hypertension group and in the group with atherosclerotic disease, respectively. On average 0.6 and 0.8 antihypertensive agents were added. In the hypertension group mean LDL-level decreased from 3.2 to 2.4 mmol/l. For the secondary prevention group mean LDL-cholesterol decreased from 3.3 to 2.1 mmol/l. In the hypertension group, the 10-year relative risk of myocardial infarction (FHRS) decreased by 28% (95% CI 25-30). The 10-year relative risk on a fatal cardiovascular event (HS) decreased by 33% (95% CI 31-36). The absolute risk decreased by 3.3% (95% CI 2.0-4.6) and 1.4% (95% CI 0.5-2.3) by using the HS. We conclude that the cardiovascular risk profile of our patients significantly improved as shown by the FHRS or the HS. These benefits were reached by a decreasing number of smokers, better blood pressure control and a lower LDL-cholesterol.

[Accelerated elimination using hemoperfusion in a patient with phenobarbital intoxication]. / Versnelde eliminatie door hemoperfusie bij een patiënte met fenobarbitalintoxicatie.

A 44-year-old female was found comatose after attempting suicide. Toxicological screening showed phenobarbital intoxication. The patient was treated symptomatically. After ten days her serum level of phenobarbital still had not decreased and she was not clinically recovered. The patient was transferred to another hospital for hemoperfusion to decrease the level of phenobarbital. After hemoperfusion the level of phenobarbital dropped significantly and the patient recovered neurologically. Phenobarbital has a long elimination half-life and for this reason it is advisable to use means to accelerate clearance until the clinical condition of the patient shows improvement. Multiple-dose activated charcoal effects the elimination of phenobarbital. If elimination needs to be speeded up, then hemoperfusion can be considered. If this technique is unavailable, hemodialysis is a good alternative.

[Retroperitoneal bleeding caused by renal angiomyolipoma]. / Retroperitoneale bloeding uit een renaal angiomyolipoma.

An 81-year-old woman presented with left-flank pain, anaemia and a fast irregular pulse while using oral anticoagulation. Diagnostic investigation revealed retroperitoneal bleeding caused by a medium-sized renal angiomyolipoma. Angiomyolipoma was also found in the contralateral kidney. No tuberous sclerosis was ascertained. Bleeding stopped after discontinuation of anticoagulant therapy. Renal angiomyolipoma is an uncommon benign tumour which is frequently associated with tuberous sclerosis. Spontaneous retroperitoneal bleeding is a potentially life-threatening complication. This type of tumour is usually found incidentally on radiological examination.

Combination of a normal D-dimer concentration and a non-high pretest clinical probability score is a safe strategy to exclude deep venous thrombosis.

BACKGROUND: Serial ultrasonography is reliable for the diagnosis of deep venous thrombosis in symptomatic patients, but the low prevalence of thrombosis in this group renders the approach costly and inconvenient to patients. We studied the clinical validity of the combination of a pretest clinical probability score and a D-dimer test in the initial evaluation of patients suspected of deep venous thrombosis. METHODS AND RESULTS: Patients with a normal D-dimer concentration (<500 fibrin equivalent units [FEU] microg/L) and a non-high probability score (<3) had no further testing. Patients with a normal D-dimer concentration and a high probability score (> or =3) underwent one ultrasonogram. Serial ultrasonography was performed in patients with an abnormal D-dimer concentration. Patients were followed for 3 months. A total of 812 patients were evaluable for efficacy. Only 1 of 176 patients (0.6%; 95% CI, 0.02% to 3.1%) with a normal D-dimer concentration and a non-high probability score developed thrombosis during follow-up. A normal D-dimer concentration and a high probability score were found in 39 patients; 3 of them (7.7%; 95% CI, 1.6% to 20.9%) had thrombosis at presentation, and one (2.8%; 95% CI, 0.07% to 14. 5%) developed pulmonary embolism during follow-up. In 306 of 597 patients (51.3%) with an abnormal D-dimer concentration, thrombosis was detected by serial ultrasonography. Six patients (2.1%; 95% CI, 0.8% to 4. 4%) developed thrombosis during follow-up. No deaths due to thromboembolism occurred during follow-up. The total need for ultrasonography was reduced by 29%. CONCLUSION: The combination of a non-high pretest clinical probability score and a normal D-dimer concentration is a safe strategy to rule out deep venous thrombosis and to withhold anticoagulation.

The role of the spleen in pancreas transplantation.

Early graft thrombosis and rejection of the graft are the two major causes of graft failure in pancreas transplantation. Inclusion of the spleen in the pancreatic graft has been purported as a possible solution to both complications, but severe graft-versus-host disease led to abolishment of this procedure. By irradiating the donor spleen ex vivo during cold storage, we successfully prevented graft-versus-host disease, allowing us to evaluate the advantages of clinical pancreaticosplenic transplantation. This study reports our experience with 12 pancreaticosplenic transplantations. Using Doppler flow measurements, we have been able to examine the hemodynamic advantages. Our results confirm the purported benefit. Vascular resistance indices in the pancreatic graft are significantly lower when the donor spleen is included. This, however, did not lower the incidence of thrombosis (2 out of 12 cases) in our study. Serial radionuclide studies with 99mTc-hexamethyl propylene amine oxime were performed for further evaluation of graft perfusion. With time the spleen uptake diminishes, compatible with atrophy of the organ. This was confirmed histologically. No indication of an immunologic advantage of transplanting the pancreas together with the spleen was found. All patients went through severe rejection crises. A transient reduction in platelet count (55-88%, mean 71%) of preoperative values was observed. This platelet drop is not seen in patients with a pancreas without spleen transplantation. We conclude that in pancreas transplantation, inclusion of the irradiated spleen has no obvious advantages for early graft thrombosis and rejection of the graft.

Compliance and reactivity of the peripheral venous system in chronic intermittent hemodialysis.

A reduced venous compliance and/or inadequate venoconstriction could impair hemodynamics during hemodialysis. Therefore, compliance and reactivity of the peripheral venous system were assessed in hemodialysis patients and controls using strain gauge plethysmography. Reactivity of the venous system towards an efferent sympathetic stimulus was assessed using a cold pressor test. Results showed that venous compliance was reduced in hypertensive hemodialysis patients compared to normotensive dialysis patients (P = 0.013) and normotensive controls (P = 0.004). After one dosage with a directly acting venodilator (nitroglycerin 5 mg s.l.) and 3 days of treatment with an alpha 1-sympathicolytic agent (Doxazosin 2 mg), venous compliance remained unaltered in hypertensive dialysis patients. During the cold pressor test, the blood pressure response, rise in noradrenaline levels and decline in venous compliance were normal in hemodialysis patients. However, their response to the Valsalva manoeuver was significantly impaired (P = 0.011) compared to healthy controls. We conclude that hypertension, not renal failure, causes the reduction of peripheral venous compliance in hemodialysis patients, for which structural factors might be responsible. Despite the existence of autonomous neuropathy, the reaction of the peripheral venous system towards an efferent sympathetic stimulus is intact in hemodialysis patients.

Perfusion imaging of pancreas allografts using technetium-99m hexamethyl propylene amine oxime.

The vascular integrity and major changes in perfusion can be determined by visual interpretation of radionuclide flow studies. We studied the potential of a new radiopharmaceutical technetium-99m hexamethyl propylene amine oxime (99mTc-HMPAO) in the particular setting of pancreas transplantation. Perfusion was measured by perfusion indices (PI). Changes in graft perfusion were estimated by three independent observers. A predefined scale from 0 to 4 was used, with 0 representing no visualisation of the graft and 4 denoting sharp countour delineation and distinct demarcation from the background. In order to investigate the relation between perfusion of the pancreas graft and its exocrine function, we measured the amylase excretion rate (AER) in the urine, expressed in units per hour. It is concluded that 99mTc-HMPAO is a suitable radiopharmaceutical for pancreas allograft imaging. For the assessment of the vascular integrity in the direct postoperative period, the scintigram is very reliable. Although a correlation between exocrine function of the graft and the perfusion score was not established, it is possible to make a clear sorting of AER measurements into different groups.

Reperfusion injury of pancreas allografts: relation to islet cell function.

It is unknown to what extent preservation and/or reperfusion may damage islet cells in pancreas allografts. In this study, the release of insulin after reperfusion was used as a marker of injury to the islet cell and compared with the best insulin secretory response (ISR) after glucagon stimulation over a period of 100 days after pancreas transplantation.

The relationship between cause of death of the kidney donor and the presence of ischemic lesions in the kidney.

Chronic ischemic lesions in the donor kidney amplify the nephrotoxic effects of cyclosporine A. With increasing age, the presence of chronic ischemic lesions in the kidney increases, and data concerning the fate of kidney grafts from older donors are conflicting. Kidney from donors with an intracerebral bleed do less well compared to kidneys from other donors. Systematic data on the relationship between donor age, cause of death and severity of chronic ischemic lesions are lacking. This study was performed to investigate this relationship.

Detection of latent human cytomegalovirus in organ tissue and the correlation with serological status.

The presence of human cytomegalovirus (HCMV) genome in spleen tissue was studied by using DNA hybridization techniques in seropositive and seronegative organ donors without clinical or laboratory confirmed HCMV infection. The serum samples of these patients were screened by latex agglutination test (LA) and enzyme linked immuno sorbent assay (ELISA) for the presence of HCMV antibodies, and confirmed by immunoblotting technique (IB). For the detection of HCMV sequences in spleen tissue dot blot DNA hybridization (DBH) using probes derived from immediate-early and late regions (ES and BH fragment respectively) of the HCMV genome were used. Samples positive in DBH were further tested by in situ DNA hybridization (ISH) using the ES probe. The number of spleen tissue specimens positive for HCMV nucleic acids indicated that HCMV may be present in human beings, even without serological evidence.

The impact of ischemic lesions in the donor kidney, donor age, recipient age and HLA (A, B, C, DR, DQ) matching on clinical course after kidney grafting.

It is generally accepted that HLA matching improves graft survival. However, there is no consensus on whether this improvement is reflected on daily clinical course. Clinical course after renal transplantation depends on many factors, such as donor age, recipient age, ischemic score in the kidney, and HLA matching. The relative contribution of these factors is unknown. Because management of the recipients in the various centers differs considerably, only a single centre study would reveal the relative contribution of all these factors. Therefore, in our centre we studied the influence of these parameters on the clinical course after renal allografting.

Prevalence of Helicobacter pylori antibodies in patients on chronic intermittent haemodialysis.

The presence of IgG antibodies against Helicobacter pylori in haemodialysis patients was studied. Furthermore the presence of antibodies in different age cohorts was compared with a population of patients suffering from non-ulcer dyspepsia and healthy blood donors. Antibodies were present in 43% of the haemodialysis patients. In the younger age groups the presence was low compared with the control populations; this difference was not present in the older age cohorts. There was an increasing prevalence of antibodies with rising age. We did not find a correlation between the height of the blood urea levels, before and after haemodialysis, and the presence of antibodies against H. pylori. In conclusion, a high blood urea level does not seem to be a risk factor, per se, for acquiring H. pylori, and the presence of the microorganism probably does not contribute, to a large extent, to the frequent dyspeptic complaints in haemodialysis patients.

Estimation of the fractional catabolic rate constants for the elimination of cytosolic liver enzymes from plasma.

Pathological elevations of the plasma activities of liver enzymes are not simply related to the quantitative release of such enzymes from the liver. Several enzymatic indices, such as the well-known de Ritis quotient, may be determined by differences in the time course of hepatic enzyme release, rather than reflecting true differences in the released quantities of various enzymes. A more quantitative use of enzymatic data is hampered by the fact that the fractional catabolic rate constants for the elimination of enzyme activities from plasma are unknown. In the present study, three of these constants are estimated by comparison of the time-activity curves in plasma with the corresponding curve of a simultaneously released, more slowly eliminated reference enzyme. This method can be applied in patients with an acute short period of hepatic enzyme release. Values obtained for the cytosolic isoforms of lactate dehydrogenase, AST and ALT are: fractional catabolic rate constant (lactate dehydrogenase isoenzyme 5) = 0.13 +/- 0.01 hr-1, fractional catabolic rate constant (cytosolic AST) = 0.088 +/- 0.016 hr-1 and fractional catabolic rate constant (cytosolic ALT) = 0.034 +/- 0.004 hr-1 (mean +/- S.E., n = 10). These values are much higher than the apparent disappearance rate constants, because of extravascular return of activity and tailing release of enzymes during the major part of the elimination phase. It is shown that these results are consistent with earlier published data on the disappearance rates from plasma of lactate dehydrogenase, AST and ALT after acute liver injury. Cumulative release of various cytosolic enzymes occurred in proportion to the corresponding activities in human control livers.