Liposomal amphotericin B in hepatic candidosis

A 4 year old girl treated with a standard chemotherapy protocol for acute lymphoblastic leukaemia developed hepatic candidosis during the consolidation phase. This relapsed after a prolonged course of amphotericin B and flucytosine. An eight week course of liposomal amphotericin produced a marked clinical improvement which was sustained for one year. A subsequent relapse was associated with transformation to myelodysplastic leukaemia.     

Elevated levels of angiogenic cytokines in the plasma of cancer patients

Although in the normal healthy organism angiogenesis is a tightly regulated process, under a variety of circumstances it may contribute to disease states. These include the growth of solid tumors, the hematogenous spread of tumor cells and the growth of metastasis. Our aim was to measure the levels of 5 angiogenic cytokines in the plasma of patients with a variety of cancers, to establish a plasmatic angiogenic profile. We prospectively obtained blood samples in citrated tubes from 40 healthy individuals and 75 patients with a variety of solid tumors. Patients who had received any form of treatment in the preceeding 6 months were excluded from the study. Plasma levels of the following 5 cytokines were determined by ELISA: vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), basic fibroblast growth factor, transforming growth factor-beta and tumor necrosis factor-alpha. In some cases, additional samples were taken 4 and 15 days after surgical removal of the tumor. Our findings demonstrate, that firstly, compared to the tumor group VEGF was almost always undetectable or present at very low levels in healthy individuals; secondly, a threshold value for HGF was found to exist between the 2 groups (healthy vs. tumor); and thirdly, there was a clear relationship between plasma levels of VEGF and HGF and extension of disease (i.e., without or with metastases). The timing of blood sampling in the post-operative period was found to be critical, particularly with regard to VEGF and HGF. The existence of a systemic angiogenic profile in the plasma of cancer patients may be useful as a diagnostic and prognostic tool and may help in the future to monitor the responses of individual patients to anti-tumor and, particularly, anti-angiogenic therapy.     

Surgical anatomy of the nose

It is imperative to know the details of the anatomy of the nose before understanding any surgical procedure performed on the nose. The details presented in this article should help the experienced and the novice surgeon accomplish the difficult task of a rhinoplasty.     

The apoptotic pathway: a target for therapy in chronic lymphocytic leukemia

Cell division and apoptosis (programmed cell death) are the two major physiological processes which control the size of cell populations. Chronic lymphocytic leukaemia arises as a result of the clonal expansion of, usually B-, lymphocytes in which a dysregulation of apoptosis leads to prolonged cell survival. The same process becomes exaggerated with increasing drug resistance, the usual cause of treatment failure in this condition. The identification of points in the apoptotic pathway at which dysregulation occurs is beginning to open up new therapeutic opportunities where the conventional cytotoxic chemotherapy approach is found to fail. Although these strategies are still in their infancy they may increase understanding of the pathogenesis of the disorder and overcome the problem of drug resistance.     

Contribution of a risk factor clinic to lipid management in patients with coronary artery disease.

The progress of a cohort of 145 patients seen between June 1986 and June 1989 was reviewed. These patients had treatment prescribed by the clinic and had data recorded over serial visits; they allowed us to determine the contribution of the risk factor clinic. Eighty-six percent had coronary artery disease. Patients were given nutritional advice, partly in groups. In addition 61% were treated with drug therapy. Seventy-four percent had modified their diet before the clinic visit but only 32% received less than 30% of energy from fat; the number rose to 67% by discharge. Sixty-four percent had a body mass index of 25 or greater, falling to 53% at discharge. Mean total cholesterol of the 145 patients was 7.9, HDL cholesterol 1.06, and total:HDL cholesterol ratio 7.7 mmol/L. Changes with clinic management were: total cholesterol -19%, HDL cholesterol +11%, total:HDL cholesterol ratio -25%, LDL cholesterol -21%. Despite these changes, levels were less than optimal for patients with coronary arterial disease in at least 50% of patients at the time of discharge. Improved results can be achieved only with a more aggressive approach to drug therapy. Recent studies in patients with coronary disease provide strong support for such a change in management.     

5-HYDROXYTRYPTAMINE-INDUCED CONTRACTION OF THE MARMOSET AORTA IS MEDIATED BY A 5-HT1-LIKE RECEPTOR

1. 5-Hydroxytryptamine (5-HT) exerts both contractile and relaxant effects in the marmoset isolated aorta, actions that are unaffected by the 5-HT₂ antagonist ketanserin. The aim of the present study was to define the receptors mediating the contractile activity of 5-HT in the marmoset aorta.
2. Contractile responses were elicited in aortic rings that were either: (i) precontracted submaximally with the thromboxane A₂ agonist U44069 in order to amplify the responses; or (ii) exposed to N ^ω-nitro- L -arginine (100 μmol/L) plus LY 53857 (0.1 μmol/L; a 5-HT₂ receptor antagonist shown previously to inhibit relaxation). The effect of 5-HT on adenosine 3',5'-cyclic monophosphate (cAMP) formation was also investigated.
3. The effects of agonists and antagonists comprised: (i) agonist potencies in the order 5-carboxamidotryptamine > 5-HT > sumatriptan > 8-hydroxy-2-(di- n -propylamino)tetralin; (ii) inhibition of contractile action of 5-HT by the 5-HT_1D antagonist GR 127935; (iii) a contractile response to methysergide; (iv) a lack of effect of tropisetron, an antagonist of 5-HT₃ and 5-HT₄ receptors; and (v) inhibition of forskolin-stimulated cAMP formation by 5-HT (in the presence of LY 53857), indicative of negative coupling to adenylate cyclase.
4. The above effects fulfil the criteria for a 5-HT₁-like receptor. In view of the previous finding that this contractile response is insensitive to ketanserin, it is concluded that the contractile effects of 5-HT in the marmoset aorta are mediated exclusively by a 5-HT₁-like receptor.