Interstitial and vascular pancreas rejection in relation to graft survival

To examine the incidence of interstitial and vascular rejection in pancreas allografts and its impact on graft survival, we studied 36 percutaneous pancreas biopsies and 10 pancreas transplantectomy specimens from 32 patients who had undergone simultaneous pancreas-kidney transplantation. Interstitial rejection (IR) was predominantly found in the biopsies, while vascular rejection (VR) was most prominent in the transplantectomies. Pancreas graft survival was significantly decreased for pancreas grafts that had suffered from vascular rejection when compared to those with only interstitial rejection. Potential rejection markers, i. e., serum amylase, glucose, creatinine, and urinary amylase, did not correlate with histological signs of rejection, although increased levels of serum amylase were, in all but one case, associated with rejection.We conclude that a percutaneous pancreas biopsy remains the most reliable method to determine pancreas rejection, and that by distinguishing between IR andVR, a pancreas biopsy may provide important diagnostic as well as prognostic information. Received: 6 March 1997 Received after revision: 5 June 1997 Accepted: 30 June 1997     

Maxillary sinusitis in adults: an evaluation of placebo-controlled double-blind trials

BACKGROUND: In general practice, acute sinusitis is frequently diagnosed and treated with antibiotics. OBJECTIVE: This study aimed to determine the evidence for the effectiveness of antibiotic treatment in acute maxillary sinusitis in adults by assessing the methodological quality of placebo-controlled double-blind randomized trials. METHOD: An evaluation by four raters through a 35-item scoring-scale for internal and external validity of all placebo-controlled double-blind randomized trials on acute sinusitis found between January 1966 and July 1996. RESULTS: Eighty-five trials were excluded because they were not placebo-controlled, double-blind, randomized, or were carried out in patients with chronic sinusitis or in children. The three remaining trials were performed in different populations (one in general practice) between 1973 and 1978. Only one study claimed superiority of antibiotic treatment. Different inclusion criteria and major outcome measures were used by the authors. The reliability of major outcome events was reported poorly or not at all and in two studies outcome measures were clinically inappropriate. The studies scored 30-62% of the maximum attainable score for internal validity and 10-20% for external validity. CONCLUSION: The effectiveness of antibiotic treatment in acute maxillary sinusitis in a general practice population is not based sufficiently on evidence.      

Toe temperature versus transcutaneous oxygen tension monitoring during acute circulatory failure

Measurements of toe temperature and transcutaneous PO₂ (P_tcO₂) have been both suggested for non-invasive assessment of peripheral blood flow in acute circulatory failure. The underlying principle of the two methods is that cutaneous vasoconstriction occurs early when tissue perfusion is altered. In 15 patients, we compared the two measurements during cardiogenic shock (27 measurements) or septic shock (29 measurements). Toe-ambiant temperature gradient and P_tcO₂ correlated well together (r=0.66, p(0.001) especially in hyperkinetic septic shock (r=0.79, p(0.001). In cardiogenic shock, toe-ambiant temperature correlated well with cardiac index (r=0.63), stroke index (r=0.64) and oxygen transport (r=0.65), and these correlations were stronger than for P_tcO₂. In septic shock, both techniques were poor indicators of blood flow indexes but P_tcO₂ rather correlated with arterial pressure (r=0.66) and left ventricular work (r=0.66). Trend evaluation of data revealed in cardiogenic shock that the increase in toe temperature usually preceded the increase in P_tcO₂. Since measurement of P_tcO₂ is technically more complicated, correlates less well with standard hemodynamic parameters and later reflects cardiovascular improvement, it has no advantage over measurement of toe temperature in circulatory shock. In cardiogenic shock, measurements of toe temperature can reliably track cardiac output changes. In septic states, however, non-invasive assessment of skin perfusion is of limited interest.     

Forced oscillation technique. Reference values for total respiratory resistance obtained with the Siemens Siregnost FD5.

Total respiratory resistance (Rrs) was measured by the application of a sine wave of airflow to the mouth at an oscillation frequency of 10 Hz. The instrument used was the Siemens Siregnost FD5. The Rrs data were correlated with height, age, sex, and weight in 73 patients and 29 healthy subjects. The patients took part in a rehabilitation program for restoration of their locomotion function. Both groups had normal lung function (VC, FEV1) and no signs of pulmonary disease. The only important determining factor for the value of the Rrs was height. The mean Rrs of 102 subjects was 0.29 +/- 0.08 kPa.1-1.s. Other studies gave values between 0.23 +/- 0.05 and 0.32 +/- 0.10 kPa.1-1.s.     

Sialic acid concentrations in the urine of men with and without renal stones

Summary It has been suggested that urinary sialidase may play a role in the formation of renal stones. The present study was therefore undertaken to compare spectrophotometrically the different types of sialic acid concentrations and sialidase activities in fresh first morning urine specimens of men (21–65 years) with (13) and without (9) calcium oxalate renal stones. Although the free urinary sialic acid concentrations of the two groups of men were statistically about the same (P=0.0614), the total (P=0.003) and bound (P=0.0012) urinary sialic acid concentrations differed significantly. Both the total and bound sialic acid concentrations were lower in the urine specimens of the stone patients than in their healthy counterparts. This decrease in urinary sialic acid concentrations was firstly thought to be the result of elevated breakdown enzymes of sialic acid, which would favour the production of pyruvate. However, spectrophotometric determinations of the endogenous pyruvate concentrations of the two types of urine specimens did not differ significantly (P=0.0708). Secondly, the decrease in total urinary total sialic acid concentration of stone patients, could be attributed to less sialic acid synthesis or less renal excretion. Therefore, the same experiments were repeated using serum of 13 patients and 9 healthy men. Conversely, the total (P=0.4425) and bound (P=0.2850) serum sialic acid concentrations were found to be similar in the two types of subjects. However, the free serum sialic acid concentration of stone patients was significantly lower than in the healthy subjects (P=0.0062). This phenomenon is also reflected in the average ratio for serum free: bound sialic acid in healthy and stone patients, 1:7.9 and 1:18.7 respectively (P=0.0009). The lower free serum sialic acid concentration may lead to lower renal excretions of sialic acid. This may explain the decrease in total urinary sialic acid concentration in stone patients. The lower bound urinary sialic acid concentrations in patients was also reflected in the urinary free: bound sialic acid ratio for healthy (1:2.3) and stone patients (1:1.3). The difference between these two groups of men was highly significant (P=0.0001). This phenomenon might be explained by the urinary sialidase activities, which was spectrophotometrically determined at 334 nm at 37°C of 11 patients with stones and 17 healthy men. The ages of both groups of men were the same (P=0.326). An increase in urinary sialidase activity was observed with the stone patients (P=0.00001) when compared to specimens of healthy men. This might explain the decrease in urinary bound sialic acid concentration of the stone group. It seems from these results that the urinary concentration of sialic acid and the activity of urinary sialidase, may play a role in the pathogenesis of the multifactorial disease, urolithiasis.     

Decrease of inorganic blood sulfate following treatment with selected antirheumatic drugs: potential consequence for articular cartilage

The elimination kinetics of inorganic blood sulfate in mice was followed for four hours after a single, oral administration of an antirheumatic drug. Sodium salicylate, aspirin, diflunisal and benorylate, all in a dose of 1.25 mmol/kg, reduced the sulfate level to the less than half that of control. This phenomenon was also demonstrated by phenylbutazone, oxyphenbutazone (both 1 mmol/kg), chloroquine diphosphate (0.6 mmol/kg) and tiaprofenic acid (0.02-0.35 mmol/kg). Niflumic acid (1.08 mmol/kg), piroxicam (0.03 mmol/kg), indomethacin (6.10(-3) mmol/kg), diclofenac (5.10(-3) mmol/kg), ketoprofen (0.2 mmol/kg), naproxen (0.08 mmol/kg) and ibuprofen (0.24 mmol/kg) possessed no sulfate lowering properties. The potential relevance of the use of sulfate lowering drugs for articular cartilage integrity is discussed in the light of what is already known about this subject.     

Nonsteroidal cardiotonics. 3. New 4,5-dihydro-6-(1H-indol-5-yl)pyridazin-3(2H)-ones and related compounds with positive inotropic activities

A series of substituted indolyldihydropyridazinones and related compounds 1-18 were synthesized and evaluated for positive inotropic activity. In rats, most of these indole derivatives produced a dose-related increase in myocardial contractility with little effect on heart rate and blood pressure. Compound 13, 4,5-dihydro-5-methyl-6-(2-pyridin-4-yl-1H-indol-5-yl)pyrazin-3(2H) -one (BM 50.0430), was further investigated in cats. The increase in contractility in this animal model was not mediated via stimulation of beta-adrenergic receptors. After oral administration of 1 mg/kg to conscious dogs, compound 13 and pimobendan were still active after 6.5 h. However, the cardiotonic effect of 13 was at least 2-fold that of pimobendan after this period of time. The structural requirements necessary for optimal cardiotonic activity within this novel class of indole derivatives are a heterocyclic aromatic ring in position 2, a hydrogen or a methyl group in position 3, and a dihydropyridazinone ring system in position 5 of the indole.     

Volumetrical measurements in vestibular schwannoma, the influence of slice thickness and patient's repositioning.

OBJECTIVE: Conservative treatment in vestibular schwannomas is mainly dependent on optimal tumor size determination. The first objective of this study was to establish interobserver and intraobserver variability and the accuracy and reproducibility of three different measurement methods: one bidimensional and two volumetrical. The second objective was to evaluate the influence of the use of different magnetic resonance imaging (MRI) slice thickness and the influence of patient's repositioning on the measurements' outcome. STUDY DESIGN: Two consecutive studies have been prospectively performed, both mainly concerning volumetrical measurements. SETTING: Both studies were performed in a tertiary academic, multidisciplinary center. PATIENTS: In the first study, 19 patients were included between March 1996 and May 2002, with a total of 52 scans. The second study comprised 14 patients. All patients in the first study had at least two MRI examinations performed according to a standard protocol (T1-weighted gadolinium-enhanced, slice thickness of 3 mm, and interslice gap of 0.3 mm). The population in the second study underwent a conservative wait and scan (W&S) treatment. METHODS: Both studies are discussed separately. In the first study, all scans were measured by four investigators, two of whom performed the measurements twice using three different methods. The first method concerns a manually performed bidimensional surface measurement along the petrous pyramid. The second method concerns a semiautomatic volumetrical measurement on a computer, relying on contour detection, and the last method concerns a fully automatic volume reconstruction also performed on a computer using different gray shade scales.All 14 patients included in the second study underwent three magnetic examinations. Three different T1-weighted gadolinium-enhanced sequences were used: the first using a slice thickness of 1 mm, the second again with 1-mm slice thickness but after having repositioned the patient. In the third sequence, a slice thickness of 3 mm was used. All scans were measured by two investigators using the three different methods, as described previously. RESULTS: The manual surface method shows large intraobserver variability, and its reproducibility is significantly lower compared with volume measurements. Because of a relatively large systematic error in small tumors, sensitivity of growth detection is low. Both volumetrical methods are hardly interobserver- and intraobserver-dependent, and the gray shade method turned out to be the most accurate. Radiologic progression is only significant at a volume increase of at least 50%. The influence of patient repositioning is negligible, whereas the use of 1-mm slice thickness seems to be superior to a 3-mm slice thickness. CONCLUSION: The volumetrical gray shade method is the most accurate method to detect early tumor progression. As tumor increase of at least 50% is needed to be able to speak of statistically significant tumor growth, the absence of radiologic progression does not mean that there is no tumor growth. Repositioning of the patient has no influence on the measurements' outcome, whereas for optimal magnetic resonance imaging examinations, a 1-mm slice thickness protocol seems to be superior.