Multi-residue screening of veterinary drugs in egg, fish and meat using high-resolution liquid chromatography accurate mass time-of-flight mass spectrometry.

The last 2 years multi-compound methods are gaining ground as screening methods. In this study a high-resolution liquid chromatography combined with time-of-flight mass spectrometry (HRLC-ToF-MS) is tested for the screening of about 100 veterinary drugs in three matrices, meat, fish and egg. While the results are satisfactory for 70-90% of the veterinary drugs, a more efficient sample preparation or extract purification is required for quantitative analysis of all analytes in more difficult matrices like egg. The average mass measurement error of the ToF-MS for the veterinary drugs spiked at concentrations ranging from 4 to 400 microg/kg, is 3.0 ppm (median 2.5 ppm) with little difference between the three matrices, but slightly decreases with increasing concentration. The SigmaFit value, a new feature for isotope pattern matching, also decreases with increasing concentration and, in addition, shows an increase with increasing matrix complexity. While the average SigmaFit value is 0.04, the median is 0.01 indicating some high individual deviations. As with the mass measurement error, the highest deviations are found in those regions of the chromatogram where most compounds elute from the column, be it analytes or matrix compounds. The median repeatability of the method ranges from 8% to 15%, decreasing with increasing concentration, while the median reproducibility ranges from 15% to 20% with little difference between matrices and concentrations. The median accuracy is in between 70% and 100% with a few compounds showing higher values due to matrix interference. The squared regression coefficient is >0.99 for 92% of the compounds showing a good overall linearity for most compounds. The detection capability, CCbeta, is within 2 times the associated validation level for >90% of the compounds studied. By changing a few conditions in the analyses protocol and analysing a number of blank samples, it was determined that the method is robust as well as specific. Finally, an alternative validation strategy is proposed and tested for screening methods. While the results calculated for repeatability, within-lab reproducibility and CCbeta show a good comparison for the matrices meat and fish, and a reasonable comparison for the matrix egg, only 27 analyses are required to obtain these results versus 63 analysis in the traditional, 2002/657/EC, approach. This alternative is suggested as a cost-effective validation procedure for screening methods.

Comprehensive screening and quantification of veterinary drugs in milk using UPLC-ToF-MS.

Ultra-performance liquid chromatography combined with time-of-flight mass spectrometry (UPLC-ToF-MS) has been used for screening and quantification of more than 100 veterinary drugs in milk. The veterinary drugs represent different classes including benzimidazoles, macrolides, penicillins, quinolones, sulphonamides, pyrimidines, tetracylines, nitroimidazoles, tranquillizers, ionophores, amphenicols and non-steroidal anti-inflammatory agents (NSAIDs). After protein precipitation, centrifugation and solid-phase extraction (SPE), the extracts were analysed by UPLC-ToF-MS. From the acquired full scan data the drug-specific ions were extracted for construction of the chromatograms and evaluation of the results. The analytical method was validated according to the EU guidelines (2002/657/EC) for a quantitative screening method. At the concentration level of interest (MRL level) the results for repeatability (%RSD < 20% for 86% of the compounds), reproducibility (%RSD < 40% for 96% of the compounds) and the accuracy (80-120% for 88% of the compounds) were satisfactory. Evaluation of the CCbeta values and the linearity results demonstrates that the developed method shows adequate sensitivity and linearity to provide quantitative results. Furthermore, the method is accurate enough to differentiate between suspected and negative samples or drug concentrations below or above the MRL. A set of 100 samples of raw milk were screened for residues. No suspected (positive) results were obtained except for the included blind reference sample containing sulphamethazine (88 microg/l) that tested positive for this compound. UPLC-ToF-MS combines high resolution for both LC and MS with high mass accuracy which is very powerful for the multi-compound analysis of veterinary drugs. The technique seems to be powerful enough for the analysis of not only veterinary drugs but also organic contaminants like pesticides, mycotoxins and plant toxins in one single method.

[The aortocaval fistula, a rare complication of an aneurysm of the abdominal aorta]. / De aortocavale fistel, een zeldzame complicatie van een aneurysma van de abdominale aorta.

Four patients, 3 men aged 73, 60 and 81 years with hemodynamic instability and 1 man aged 80 with abdominal symptoms and breathlessness appeared to have an arteriovenous fistula secondary to spontaneous rupture of an atherosclerotic aneurysm: between the aorta and the V. cava inferior or between the A. and the left V. iliaca communis. One patient died, one patient had postoperative decompensatio cordis, one suffered a deep vein thrombosis and the 4th recovered without symptoms. The presence of an aortocaval fistula has to be considered in patients with a symptomatic abdominal aneurysm with a harsh bruit heard over the abdomen, signs of high venous pressure and peripheral hypoperfusion. When no rupture of the aneurysm is found at laparotomy in symptomatic patients, the presence of a fistula is rare, but has to be considered. Furthermore, a fistula can be the underlying cause of therapy-resistant heart failure or acute renal dysfunction. Pre-operative identification can lead to decrease of morbidity and mortality of the phenomenon.

The clinical features of bipolar depression: a comparison with matched major depressive disorder patients.

BACKGROUND: Despite a resurgence of interest in the treatment of bipolar depression, there have been few controlled studies of the clinical characteristics of this condition. Identification of any distinctive clinical "signatures" of bipolar depression would be helpful in determining treatment options in the clinical setting. METHOD: From a cohort of 270 inpatients and outpatients assessed in detail during a DSM-IV major depressive episode, 39 bipolar I disorder patients were identified and closely matched with 39 major depressive disorder patients for gender, age, and the presence or absence of DSM-IV melancholic subtype. Patients were compared on a broad range of parameters including the Hamilton Rating Scale for Depression (depression severity), 54 depressive symptoms, the Newcastle Endogenous Depression Diagnostic Index, 3 family history items, 2 physical health items, the CORE scale (psychomotor disturbance), and 5 history items. RESULTS: Although the bipolar patients were no more severely depressed than the major depressive disorder controls, they were more likely to demonstrate psychomotor-retarded melancholic and atypical depressive features and to have had previous episodes of psychotic depression. These findings were largely duplicated even when the population was confined to those with DSM-IV melancholia. CONCLUSION: The clinical admixture of psychomotor-retarded melancholic signs and symptoms, "atypical" features, and (less frequently) psychosis may provide a "bipolar signature" in clinical scenarios when there is uncertainty concerning the polarity of a depressive presentation.

Randomized trial of stripping versus high ligation combined with sclerotherapy in the treatment of the incompetent greater saphenous vein.

This prospective randomized study compared the treatment of greater saphenous vein insufficiency by stripping and local avulsions of varicose veins with high ligation of the saphenofemoral junction (crossectomy) combined with sclerocompression therapy. Of 156 consecutive patients, 89 legs were randomly allocated to stripping and 92 to high ligation. At follow-up of 3 months and 1, 2, and 3 years after treatment, clinical and Doppler ultrasound results, and complaints and cosmetic results, as judged by the patient and the surgeon, were scored. At 3 years, 69 limbs in the stripping group (78%) and 73 limbs in the ligation group (79%) were available to follow-up. The cosmetic results, both judged by the patient and the surgeon, were significantly better (P < 0.05) in the stripped limbs than in the limbs with high ligation and sclerotherapy. Clinical and Doppler ultrasound evidence of reverse flow in the saphenous vein was significantly less (P < 0.001) after the stripping operation. The results of treatment of isolated saphenous vein insufficiency by stripping operation, therefore, were superior to those obtained by high ligation combined with sclerotherapy.

Photoplethysmography in the diagnosis of superficial venous valvular incompetence.

Photoplethysmography was compared with clinical investigation combined with Doppler ultrasonography in the diagnosis of superficial venous valvular incompetence of the lower limb. In 268 consecutive patients, 536 limbs were investigated. A total of 22.1 per cent of the photoplethysmographic investigations were uninterpretable because they did not allow reliable determination of the refilling time. Agreement between clinical investigation combined with Doppler ultrasonography and photoplethysmography was found to be poor (kappa = 0.30). These results suggest that photoplethysmography is not the non-invasive method of choice for routine evaluation of superficial venous valvular incompetence of the leg.

Surgical implications of drug-induced rhabdomyolysis.

Four cases are described of acute non-traumatic rhabdomyolysis with subsequent development of a compartmental syndrome, requiring extensive fasciotomies. All the patients were young male alcoholics who were taking benzodiazepines as part of an addiction treatment programme. In this risk group clinicians should be aware of two serious complications of non-traumatic rhabdomyolysis: acute renal failure and compartmental syndrome.

Rapid evolution of a mycotic aneurysm of the abdominal aorta due to Salmonella.

The case history is presented of a patient admitted with a Salmonella infection and the development of a mycotic aortic aneurysm within two weeks. The patient could be successfully treated by resection of the aneurysm, primary prosthetic in-situ grafting and antibiotics.

A prospective study of ultrasonography in the diagnosis of appendicitis.

The diagnosis of appendicitis is frequently difficult. We studied prospectively the diagnostic accuracy and clinical impact of abdominal ultrasonography in 111 consecutive patients thought to have appendicitis. Ultrasonography was performed with small high-resolution, linear-array transducers, with the abdomen compressed to displace or compress bowel and fat. Among 52 patients later shown in surgery to have appendicitis, ultrasonography was unequivocally positive in 39 (sensitivity, 75 percent). Of 31 patients in whom appendicitis was definitely excluded, none had a positive ultrasound examination (specificity, 100 percent). The sensitivity in those with a perforated appendix (28.5 percent) was much lower than in those with acute nonperforating appendicitis (80.5 percent) or appendiceal mass (89 percent), but the low sensitivity did not influence clinical management, since the need for surgery in patients with a perforated appendix was clinically obvious. Ultrasonography resulted in changes in the proposed management in 29 of the 111 patients (26 percent). It also led to the correct diagnosis in the 16 patients who were found to have a disease other than appendicitis. We conclude that ultrasonography is a useful aid in the diagnosis of appendicitis.

Radiation appendicitis: demonstration with graded compression US.

In a patient who had received presurgical radiation therapy for extensive rectal carcinoma, ultrasonography with graded compression disclosed an inflamed appendix. The patient had no clinical signs of acute appendicitis. At laparotomy for resection of the rectal carcinoma, the appendix appeared grossly abnormal and was removed. Pathologic examination showed severe radiation enteritis of the appendix. The sonographic appearance of radiation appendicitis closely resembled that of acute appendicitis.