Activity of beta-lactamase in Pseudomonas aeruginosa as studied by HPLC

Mutants with increased resistance were selected from a clinical isolate of Pseudomonas aeruginosa using ceftazidime, piperacillin and carbenicillin. The MICs of these antibiotics and of ticarcillin were determined for the parent strain and for the selected mutants. Subsequently, cell-free extracts of the strains were prepared and the rates of hydrolysis of several beta-lactam substrates by the extracts were determined by HPLC procedures. It appeared possible to determine beta-lactamase activities in the crude cell extracts at the low substrate concentrations which may be attainable in the periplasm of Gram-negative bacteria. It is concluded that the increased drug MICs for mutants selected with ceftazidime or piperacillin, but not for those selected with carbenicillin, were caused by increased chromosomal beta-lactamase activity.     

Relaxation times of choline, creatine and N-acetyl aspartate in human cerebral white matter at 1.5 T

Several studies have investigated the T1 and T2 relaxation time of choline, creatine and N-acetyl aspartate in cerebral white matter in normal human subjects. However, these studies demonstrate a large variation in T1 and T2 values. In the present study, relaxation times of choline, creatine and N-acetyl aspartate were determined in cerebral white matter in 15 control subjects (age 21 +/- 2 y, mean +/- SD) at 1.5 T. Using PRESS, seven or eight data points were obtained to fit the T1 and T2 relaxation curves to, respectively. The mean voxel size was 14 cm3. The T1 relaxation times of choline, creatine and N-acetyl aspartate were 1091 +/- 132 (mean +/- SD), 1363 +/- 137 and 1276 +/- 132 ms. The T2 relaxation times were 352 +/- 52, 219 +/- 29 and 336 +/- 46 ms, respectively.     

Carcinoid tumors of the intestines: developments in the Netherlands for diagnosis and palliative treatment

Carcinoid tumours in the intestine are slowly growing neuroendocrine tumours. Patients as a rule report symptoms of the carcinoid syndrome: attacks of diarrhoea and of flushing. When the earliest symptoms manifest themselves, metastases are already present, virtually always localized in the liver. At a late stage, heart failure may occur, difficult to treat and caused by fibrosis of the tricuspid valve in the presence of protractedly raised blood serotonin levels. To diagnose carcinoid tumours, use is made of radioactive substances binding to hormone receptors such as 131I-MIBG and 111-In-octreotide. When multiple metastases exist, only palliative treatment is possible. The drugs used are the somatostatin analog octreotide, interferon alpha, radioactive MIBG and non-radioactive MIBG; these drugs may also be used in combination. The therapies mentioned have approximately the same effect: symptoms improve in 60-80%, while 30-50% show a biochemical response, i.e. decrease of the number of breakdown products in the urine of the hormones produced by the tumour; tumour size decreases in 0-12%.     

A comparison in cosmetic outcome between per-operative interstitial breast implants and delayed interstitial breast implants after external beam radiotherapy.

BACKGROUND AND PURPOSE: Interstitial implants for brachytherapy boost in the breast conserving therapy of breast cancer can be performed in two ways; implants during the tumor excision (per-operative implants) or after the external beam therapy (delayed interstitial implants). Differences in cosmetic outcome were investigated. PATIENTS AND METHODS: Cosmetic results in 47 patients having a per-operative implant were compared to 123 patients having a delayed interstitial implant in a matched case-control study. Cosmesis was scored on a four-point-scale varying from 0 (excellent) to 3 (poor). RESULTS: After mean follow-up of 63 months, three observers found no difference in cosmetic outcome between the two groups after adjustment for variables found to be related with cosmesis (difference in mean score 0.50, P=0.26). Implant volume at 100% isodose was not found to differ (P=0.084) between the per-operative group (mean 102 cm3, S.D. 34 cm3) and the delayed group (mean 93 cm3, S.D. 29 cm3). CONCLUSIONS: Performing per-operative implants has not led to smaller implants. The method of performing brachytherapy does not result in marked differences in cosmetic outcome.     

Cerebral metabolic changes in patients with a symptomatic occlusion of the internal carotid artery: a longitudinal 1H magnetic resonance spectroscopy study

The objective of this 1H magnetic resonance spectroscopy study was to investigate the time course of the brain metabolites N-acetyl-aspartate (NAA), choline, and lactate in patients with transient or minor disabling neurological deficits associated with an occlusion of the internal carotid artery (ICA). Fifty patients had had symptoms of hemispheric ischemia, and 16 had suffered symptoms of retinal ischemia. Single-voxel proton spectra were obtained from uninfarcted cerebral regions on three occasions: 0-6, 6-12, and 12-18 months after symptoms. Reference values were obtained from 29 control subjects. In the 0-6 month period, patients with hemispheric ischemia showed a significantly lower NAA/creatine ratio in the hemisphere ipsilateral to the ICA occlusion, compared with control subjects and patients with retinal ischemia, and a significantly higher choline/creatine ratio, compared with control subjects. The prevalence of lactate did not differ significantly between patient groups. In the following time periods, the NAA/creatine ratio in patients with hemispheric ischemia tended to return to control values and no longer differed from that in patients with retinal ischemia; the choline/creatine ratio decreased significantly and returned to control values. These results demonstrate that cerebral metabolism is altered in patients with an ICA occlusion who have had a hemispheric ischemic event, but returns (choline) or tends to return (NAA) to control values over time. The metabolic changes occur primarily in the hemisphere ipsilateral to the symptomatic ICA occlusion and are related to the occurrence of the hemispheric ischemic event.     

Relationship between myeloperoxidase promotor polymorphism and disease severity in sarcoidosis

Previously, we demonstrated that the number of polymorphonuclear neutrophils (PMNs) in bronchoalveolar lavage fluid (BALF) is useful in distinguishing sarcoidosis patients with a favorable outcome from those having a more severe course of disease. Neutrophils contain the oxidant-generating enzyme myeloperoxidase (MPO). Cellular levels of MPO can be influenced by functional promotor polymorphisms, ?463G/A and ?129G/A, which may modify disease severity.     

ANCA and anti-GBM antibodies in diagnosis and follow-up of vasculitic disease

In the last decade, serological detection of anti-neutrophil cytoplasmic antibodies (ANCA) and of anti-glomerular basement membrane (GBM) antibodies has tremendously facilitated the diagnosis of small vessel vasculitides. Once diagnosed, these diseases have proven to be treatable. However, in contrast to anti-GBM disease, ANCA-associated vasculitides are chronic diseases with a high relapse rate. Since morbidity in ANCA-associated vasculitides is dictated by the frequency and severity of relapses, much health benefit would be achieved if a relapse could be prevented or early treatment started. Increases in ANCA titers and persistently high ANCA levels indicate a high risk of relapse and warrant clinical evaluation of the patient for signs of relapse. This review will focus on the value of ANCA and anti-GBM antibody testing in diagnosis and on the importance of these tests in follow-up of disease.