Persevering syndrome of inappropriate antidiuretic hormone secretion after traumatic brain injury.

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a known cause of hyponatremia, caused by excessive ADH secretion which, in turn, leads to water retention. SIADH has been associated with multiple etiologies, one of which is traumatic brain injury (TBI). Most cases of SIADH after TBI describe a course in which hyponatraemia develops several days to weeks after the trauma and then resolves within a few weeks. We demonstrate a case of SIADH after TBI, which persisted several years after initial presentation, but eventually did resolve spontaneously after five years.

Simultaneous determination of fentanyl and midazolam using high-performance liquid chromatography with ultraviolet detection.

When measuring fentanyl and midazolam simultaneously in the same plasma sample with standard high-performance liquid chromatography-ultraviolet (HPLC-UV) detection, overlap of the fentanyl peak by the midazolam peak occurs, which makes fentanyl determination impossible. We tested the hypothesis that by acidifying the methanol mobile phase with 0.02% perchloric acid, 70%, it would be possible to separate both peaks. The UV detector was set at 200 nm. Calibration curves for fentanyl (range 0-2000 pg/ml) and midazolam (range 0-400 ng/ml) were linear (r>0.99). The detection limits were 200 pg/ml (fentanyl) and 10 ng/ml (midazolam). Precision and accuracy for intra- and inter-assay variability as well as in-line validation with quality control samples (QCS) were acceptable (<15 and 20%, respectively), except for fentanyl QCS of 200 pg/ml (17.8% precision). Although less sensitive than gas chromatography-mass spectrometry (GC-MS), reliable measurements of fentanyl, simultaneously with midazolam, can be performed with this HPLC-UV system.

Differences in fluid and solute transport between diabetic and nondiabetic patients at the onset of CAPD.

Loss of transcapillary ultrafiltration (TCUF) can occur during continuous ambulatory peritoneal dialysis (CAPD) and may be caused by exposure to the high glucose concentrations in the dialysate, leading to glycation of water channels in the endothelial cells of the peritoneal microvessels. If this hypothesis is correct, diabetic patients should have lower TCUF rates at the onset of CAPD than nondiabetic controls. Such a difference should disappear during longer-duration CAPD because of the continuous glucose exposure in both groups, induced by the high glucose concentrations in the dialysate. Therefore, the standard peritoneal permeability analysis of 11 diabetic (mean age 48 years, range 33-70 years) and 11 nondiabetic patients (mean age 49 years, range 36-69 years) matched for sex, age, and duration of CAPD were studied shortly after the onset of CAPD treatment (mean duration 162 vs 131 days) and one year later. No differences were found in solute transport or protein clearances between the two groups at the onset of CAPD. The TCUF rate was lower in the diabetic patients: 0.9 mL/min (0.09-2.25) versus 1.51 mL/min (0.97-2.44), p = 0.01. The other parameters of fluid transport were not different. The mean osmotic pressure gradient, exerted by albumin and glucose, was 1.72 mmHg in the diabetic patients and 5.44 mmHg in the controls (p = 0.0004). No differences were found in peritoneal permeability, including TCUF, after one year between the two groups. In conclusion, the TCUF rate was lower in diabetic patients compared to nondiabetics only shortly after the onset of CAPD. These results suggest that long-term exposure to high glucose concentrations in diabetics prior to CAPD may cause changes in capillary wall aquaporins, similar to long-term exposure to high glucose concentrations in the dialysate in CAPD.

Validation and nephrotoxicity of a simplified once-daily aminoglycoside dosing schedule and guidelines for monitoring therapy.

There is no established dosing schedule for once-daily aminoglycoside dosing regimens, and accepted guidelines for monitoring therapy are lacking. We derived a simplified schedule from the Hull and Sarubbi (J. H. Hull and F. A. Sarubbi, Ann. Intern. Med. 85:183-189, 1976) nomogram, for which efficacy and safety in a once-daily dosing regimen were previously demonstrated, and prospectively followed serum aminoglycoside levels in patients. The standard treatment was gentamicin or tobramycin at 4 mg/kg of body weight given intravenously once daily. When the renal function was decreased, the daily dose was reduced, as follows: for an estimated creatinine clearance of between 50 and 80 ml/min, the daily dose was 3.25 mg/kg, for an estimated creatinine clearance of between 30 and 50 ml/min, the daily dose was 2.5 mg/kg, and for an estimated creatinine clearance of below 30 ml/min, the daily dose was 2 mg/kg. A total of 221 patients were studied (184 received gentamicin and 37 received tobramycin). First trough levels above 2 mg/liter were recorded in 11% of the patients, and they all had a baseline creatinine clearance below 50 ml/min, or a substantial decrease in clearance between enrollment and the day that the trough level was obtained. A peak level below 6 mg/liter was recorded in 6% of the patients, and half of them received the lowest daily dose. Twenty-five of the 179 evaluable patients (14%; 95% confidence interval, 9 to 19%) fulfilled the criteria for nephrotoxicity. In a multiple regression analysis, the duration of treatment and the use of other nephrotoxic antibiotics or high-dose furosemide, but not trough levels, were significant risk factors. Since the meaning of low peak levels is unclear and since most studies with multiple daily regimens confirm the lack of an association between trough levels and toxicity, we believe that monitoring of serum drug levels can be restricted to monitoring of trough levels in patients with a creatinine clearance below 50 ml/min or with a deteriorating renal function.

Relationship of steady state and ambulatory blood pressure variability to left ventricular mass and urinary albumin excretion in essential hypertension.

A relationship exists between blood pressure and cardiovascular morbidity and mortality. Recent data suggest that the variability of blood pressure is also related to hypertensive target organ damage. We studied the relationship of ambulatory daytime and night-time and supine beat-to-beat Finapres blood pressure variability to left ventricular mass index (LVMI) and urinary albumin excretion (albumin/creatinine ration: ACR) in 33 hypertensive patients, untreated for more than 3 months. In a multiple stepwise regression model the strongest relationship with the LVMI existed for night-time systolic pressure (R = 0.46, multiple regression coefficient: 0.90 +/- 0.26 P < .01) and daytime diastolic blood pressure variability (multiple R increased to 0.60, multiple regression coefficient 3.16 +/- 1.18, P < .05). Log ACR had the strongest relationship to ambulatory systolic daytime pressure (R = 0.40, multiple regression coefficient 0.0093 +/- 0.0040, P < .05) and the variability of diastolic Finapres blood pressure (multiple R increased to 0.52, multiple regression coefficient 0.081 +/- 0.0036, P < .05). Both ambulatory and steady state blood pressure variability are related to early hypertensive target organ damage. This relationship exists independent of the height of blood pressure .

Office, nurse, basal and ambulatory blood pressure as predictors of hypertensive target organ damage in male and female patients.

The objective of this study was to assess the value of two substitutes for ambulatory blood pressure (BP) monitoring: nurse-measured BP and BP measured by an automated device during 1 h resting in the clinic (basal BP). Hypertensive patients in an academic out-patients clinic were selected consecutively. We compared the relation of indices of early target organ damage (echocardiographically determined left ventricular mass index (LVMI) and urinary albumin excretion (expressed as albumin/creatinine ratio: ACR) to physician measured and nurse measured basal and ambulatory BP. The relation of BP to LVMI and the logACR were also studied for both sexes separately. Sixty-two patients (28 men, 34 women) were included, all untreated for >3 months. Systolic office BP was not significantly related to the LVMI (r2 = 0.04, P > 0.05), whereas nurse measured (r2 = 0.11, P < 0.05), basal (r2 = 0.13, P < 0.01) and ambulatory daytime (r2 = 0.13, P < 0.05) and night time (r2 = 0.17, p < 0.001) SBP did have a significant relation to LVMI. There was no difference in the relation of office, nurse, basal or ambulatory BP to logACR. In contrast to the highly significant relation of SBP to LVMI for male patients (day: r2 = 0.29, P < 0.01, night: r2 = 0.46, P < 0.001) this relation was non-existent for female patients (day: r2 = 0.09, P > 0.05, night: r2 = 0.02, P > 0.05). The relation between BP and logACR did not differ between the sexes. We conclude that: (1) to some degree nurse measured and basal BP may be considered as better predictors of early hypertensive target organ damage than physician measured BP; and (2) there is a pronounced sex difference in the relation of BP to left ventricular mass.

[Sarcoidosis of the heart]. / Sarcoïdose van het hart.

In 2 patients arrhythmias and conduction disorders were the first symptoms at presentation of cardiac sarcoidosis. One patient with severe conduction disorders showed normalisation of the EKG during steroid treatment. The other patient developed an overall cardiomyopathy and the arrhythmia was treated with conventional drugs. The frequency of cardiac involvement in sarcoidosis is much higher than that of clinical symptoms of sarcoid heart disease. Cardiac sarcoidosis is increasingly diagnosed in the last few decades. In most cases, it presents with sudden death, arrhythmia, conduction disorders or cardiomyopathy. The main diagnostic pathological feature is evidence of noncaseating granulomas, but mononuclear cell infiltration and focal interstitial fibrosis have also been found. The basal part of the interventricular septum is particularly prone to involvement. If conventional therapy in clinically important cases proves inadequate, steroid therapy should be added. It is recommended to make an EKG in every patient presenting with sarcoidosis even in the absence of cardiac symptoms. Sarcoid heart disease should be considered in every patient with diagnostic sarcoidosis and heart disease but also in every case of difficult heart disease without an obvious aetiology. Because of the relatively early age at onset, life expectancy is shortened.

Intrabiliary rupture of a hydatid cyst of the liver with concomitant intraperitoneal rupture into the lesser sac.

A case is reported of a young man of Moroccan origin, admitted with fever, aerobilia and an epigastric mass. Laparotomy revealed a suppurated hydatid cyst extending from the left lobe of the liver, which had ruptured into the left hepatic duct and intraperitoneally, into the lesser sac. A left hepatic lobectomy was performed. Gas producing micro-organisms were cultured from the cyst contents whereas no viable scolices were demonstrated. Medical therapy with mebendazole was instituted postoperatively. Six months later, the patient underwent subtotal pancreaticoduodenectomy because of an obstructive, lymphoblastic non-Hodgkin lymphoma in the ampullary region. One year after the initial operation, there were no signs of recurrence of the hydatid disease.