Nocardia farcinica: life-threatening chorioiditis under systemic immunosuppression

BACKGROUND: Immunosuppressed patients occasionally suffer from a multifocal infection with Nocardia. It is important to distinguish Nocardia farcinica from Nocardia asteroides, because of different sensitivity against antibiotics. PATIENT AND METHODS: A 40-year-old patient with polycystic renal disease successfully underwent a kidney transplantation without complications. Immunosuppression consisted of: corticosteroids, azathioprin and ciclosporin A. Ten weeks later he developed acute choroiditis with consecutive retinal detachment and neovascular glaucoma in one eye. In addition, 14 weeks after transplantation CT scans revealed multiple cerebral abscesses. RESULTS: In the course of the disease Nocardia farcinica (N. f.) was identified by cerebral stereotactic biopsy of a cerebral lesion, histological examination of the enucleated globe and sputum culture. Histologically filamentous, eosinophilic organisms were found. Microbiology identified aerobic actinomycetes in cultures and Nocardia farcinica by PCR. Therapeutically the combination of vancomycin, ampicillin, and sulbactam was successful. CONCLUSION: In immunosuppressed patients Nocardia farcinica can become life-threatening. One of the first manifestations may be a choroiditis. Infection of the respiratory tract followed by hematogenous spread is the common way of systemic nocardiosis. Biopsy followed by identification of species by PCR is recommended because of the specific therapeutic strategies associated with each species.     

Nystagmus in suprasellar tumors: recent advances in diagnosis and therapy

Congenital and acquired nystagmus, particularly pendular and jerk nystagmus, see-saw nystagmus and spasmus nutans, may be the presenting sign of a suprasellar mass lesion.(1) The large variety of different suprasellar mass lesions requiring quite different therapeutic measures necessitates exact histological diagnosis for optimal therapeutic strategy planning.(2) Stereotactic tumor biopsy has become a well-established diagnostic approach, combining minimal surgical trauma with a high degree of diagnostic safety. Particularly in the two most frequent suprasellar mass lesions - craniopharyngiomas and pilocytic astrocytomas - accurately planned stereotactic drainage of tumor cysts combined with radiotherapy and/or stereotactic radiosurgery allows successful decompression and tumor control as well as maximum preservation of visual and endocrinological functions when compared with conventional surgical procedures.(2-11)     

Fluvoxamine augmentation of olanzapine in chronic schizophrenia: pharmacokinetic interactions and clinical effects

Olanzapine is a substrate of the cytochrome P450 enzyme (CYP) 1A2. In this study, pharmacokinetic interactions and clinical effects of adding the CYP1A2 inhibitor fluvoxamine to steady-state olanzapine was examined in patients suffering from schizophrenia. Eight patients had been treated for at least 3 months with 10 to 20 mg/day olanzapine. Fluvoxamine (100 mg/day) was added (week 0) to the olanzapine treatment and continued for 8 weeks. Concentrations of olanzapine and its metabolite N-desmethylolanzapine and of fluvoxamine were analyzed at weeks 0, 1, 4, and 8. Addition of fluvoxamine resulted in a 12% to 112% ( < 0.01) increase of olanzapine from 31 +/- SD 15 ng/mL (week 0) to 56 +/- 31 ng/mL (week 8) in all patients. N-desmethylolanzapine concentrations were not significantly changed ( > 0.05). Fluvoxamine concentrations were 48 +/- 26 ng/mL on week 1 and 83 +/- 47 ng/mL on week 8. It is concluded that fluvoxamine affects olanzapine degradation and thus increases olanzapine concentrations. Although the combination was well tolerated in this sample and the negative symptom response appeared to be favorable in at least five patients, the combination therapy of olanzapine and fluvoxamine should be used cautiously and should be controlled by therapeutic drug monitoring to avoid olanzapine-induced side effects or intoxications.     

Intravascular granulocyte aggregates caused by the selectin-binding carbohydrate fucoidin in pig kidneys

1. Renal postischaemic reperfusion injury constitutes a significant problem after kidney transplantation. The polysaccharide fucoidin improves postischaemic function in lamb hearts, presumably by blocking selectin-mediated leucocyte adhesion. 2. In the present study, eight pairs of ischaemic pig kidneys were reperfused in an ex vivo model with autologous blood with or without fucoidin (100 mg/L). 3. Fucoidin resulted in a significant decrease in renal blood flow (45 +/- 5 vs 178 +/- 22 mL/min per 100 g; P < 0.001) and increased vascular resistance (3.80 +/- 0.07 vs 0.60 +/- 0.12 mmHg/mL per min per 100 g; P < 0.001). 4. Histological examination revealed granulocyte emboli in afferent glomerular arteries in five of six fucoidin-treated kidneys and in one of six controls (Fisher's exact test; P < 0.001). 5. In vitro experiments with human granulocytes showed that large granulocyte aggregates were induced by fucoidin at concentrations similar to those used in reperfused kidneys, whereas slightly lower doses of fucoidin prevented l-selectin-dependent homotypic granulocyte adhesion. 6. The formation of embolizing granulocyte aggregates defines a narrow therapeutic range for fucoidin and calls into question its experimental use as an inhibitor of selectin-mediated leucocyte adhesion.     

Tissue-specific regulation of canine intestinal and hepatic phenol and morphine UDP-glucuronosyltransferases by beta-naphthoflavone in comparison with humans

UDP-glucuronosyltransferases (UGTs) are regulated in a species- and tissue-dependent manner by endogenous and environmental factors. The present study was undertaken to further our knowledge about regulation of UGTs in dogs, a species widely used in preclinical safety evaluation. beta-Naphthoflavone (BNF) was selected as a known aryl hydrocarbon receptor agonist and antioxidant-type inducer. The latter group of inducers is intensively investigated as dietary chemoprotectants against colon cancer. Dog UGTs were investigated in comparison with related human UGTs by examples, (i) expression of dog UGT1A6, the first sequenced dog phenol UGT, and (ii) morphine UGT activities, responsible for intestinal and hepatic first-pass metabolism of morphine. The following results were obtained: (i) dog UGT1A6 was found to be constitutively expressed in liver and marginally increased by BNF treatment. Expression was low in small intestine but ca. 6-fold higher in colon than for example in jejunum. Conjugation of 4-methylumbelliferone, one of the substrates of dog UGT1A6, was also enhanced 7-fold in colonic compared to jejunal microsomes. (ii) Compared to the corresponding human tissues, canine 3-O- and 6-O-morphine UGT activities were found to be >10-fold higher in dog liver and ca. 10-fold lower in small intestinal microsomes. Small intestinal morphine and 4-hydroxybiphenyl UGT activities appeared to be moderately (2- to 3-fold) induced by oral treatment with BNF. (iii) In contrast to dogs, morphine UGT activities were found to be similar in homogenates from human enterocytes and liver. The results suggest marked differences in tissue-specific regulation of canine vs. human hepatic and intestinal phenol or morphine UGTs.     

Isobolographic analysis of non-depolarising muscle relaxant interactions at their receptor site

Administration of certain combinations of non-depolarising muscle relaxants produces greater than expected neuromuscular blockade. Synergistic effects may be explained by drug interactions with the postsynaptic muscle nicotinic acetylcholine receptor. To investigate this hypothesis, the adult mouse muscle nicotinic acetylcholine receptor (alpha(2)beta delta epsilon) was heterologously expressed in Xenopus laevis oocytes and activated by the application of acetylcholine (10 microM). The effects of five individually applied muscle relaxants and six combinations of structurally similar and dissimilar compounds were studied. Drug combinations containing equipotent concentrations of two agents were tested and dose-response curves were determined. All compounds tested alone and in combination produced rapid and readily reversible, concentration-dependent inhibition. Isobolographic and fractional analyses indicated additive interactions for all six tested combinations. These findings suggest that synergistic neuromuscular blocking effects, observed for the administration of certain combinations of muscle relaxants, do not result from purely postsynaptic binding events at the muscle nicotinic acetylcholine receptor, but rather from differential actions on pre- and postsynaptic sites.