Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome characterised by the development of retinal and central nervous system haemangioblastomas, renal cell carcinoma (RCC), phaeochromocytoma and pancreatic tumours. The VHL disease gene maps to chromosome 3p25-p26. To investigate the mechanism of tumourigenesis in VHL disease, we analysed 24 paired blood/tumour DNA samples from 20 VHL patients for allele loss on chromosome 3p and in the region of tumour suppressor genes on chromosomes 5, 11, 13, 17 and 22. Nine out of 24 tumours showed loss of heterozygosity (LOH) at at least one locus on chromosome 3p and in each case the LOH included the region to which the VHL gene has been mapped. Chromosome 3p allele loss was found in four tumour types (RCC, haemangioblastoma, phaeochromocytoma and pancreatic tumour) suggesting a common mechanism of tumourigenesis in all types of tumour in VHL disease. The smallest region of overlap was between D3S1038 and D3S18, a region that corresponds to the target region for the VHL gene from genetic linkage studies. The parental origin of the chromosome 3p25-p26 allele loss could be determined in seven tumours from seven familial cases; in each tumour, the allele lost had been inherited from the unaffected parent. Our results suggest that the VHL disease gene functions as a recessive tumour suppressor gene and that inactivation of both alleles of the VHL gene is the critical event in the pathogenesis of VHL neoplasms. Four VHL tumours showed LOH on other chromosomes (5q21, 13q, 17q) indicating that homozygous VHL gene mutations may be required but may not be sufficient for tumourigenesis in VHL disease.

A series of novel ammonium derivatives were synthesized and examined for their antimicrobial efficacy. Comparison of antimicrobial spectrum revealed that compounds 9, 11, 16 and 23 had strong potential against pathogens in vitro. Cytotoxicity results showed compound 9 to be least toxic, it is non-toxic to A549 and U87 cells in MTT assay and exhibits marginal toxicity (15-20%) to human erythrocytes at a concentration of 1000 μg/ml as compared to 100% lysis of cells by 31.25 μg/ml of the standard drug amphotericin B. This compound has MIC values in the range of 1.95-31.25 μg/disc in DDA against different pathogens and may considered to be an important lead antimicrobial molecule for further exploration.

• High-flow nasal oxygen therapy (HFNOT) provides a valuable triad of humidity, high FI O2 , and improved patient compliance.

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