Hereditary Haemorrhagic Telangiectasia (HHT) Marked by ACVRL1C1120T Variant Displays Hypopigmented Naevi and Frequent Bleeding Episodes if CYP2C9 Co-Mutated: Clinical Notes & Rationale of Patient Registry.

Hereditary haemorrhagic telangiectasia (HHT) exhibits considerable phenotypic heterogeneity. Therefore, precise mutation screening and evaluation of patient risk must be determined in every HHT family. We present an HHT-2 case with an initial life-threatening bleeding episode that led to identification of a relatively large HHT family. Exome sequencing of the family members determined HHT-associated ACVRL1C1120T variant resulting in Arg374Trp substitution at the Ser/Thr-kinase domain region. The affected members display typical epistaxis symptomatology from early childhood resulting in sideropoenia. In addition, the HHT patients also displayed dermatology findings such as facial teleangiectasias and trunk/limb white spots representing post-inflammatory hypopigmentation. Interestingly, co-segregating with modifying cytochrome P450 (CYP2C) variant in the HHT patients led to NSAID intolerance marked by increased frequency of bleeding episodes. No arterial-venous malformation of the visceral organs and brain or association with cancer were observed. The heterogeneity of clinical presentation and the role of other variants support the need of regular patient monitoring and development of a nation-wide patient registry.

Laparoscopic pyeloplasty and pyelopyelostomy for ureteropelvic junction obstruction in a duplicated collecting system.

Ureteropelvic junction obstruction can be associated with renal anomalies. We present a case of symptomatic ureteropelvic junction obstruction associated with a duplicated collecting system that was successfully treated by laparoscopic pyeloplasty and concomitant pyelopyelostomy. The operative time was 210 minutes, and the blood loss was 20 mL. The inpatient stay was 4.5 days, and the patient returned to work after 28 days. Subsequent renograms confirmed improvement in renal function and resolution of obstruction. After 1 year, the patient remained asymptomatic. This is a feasible minimally invasive procedure for this condition that requires advanced reconstructive and intracorporeal suturing skills.

Tumorigenicity, oncogene transfection, and radiosensitivity.

PURPOSE: Reports that the incorporation of exogenous oncogenes confer radioresistance have excited interest and controversy. We investigate whether human cell lines transformed to a malignant phenotype by gamma-rays or by chemicals became radioresistant. MATERIALS AND METHODS: Rodent intestinal epithelial cells immortalized by the HPV virus, human immortalized bronchoepithelial cells and their malignant counterparts transformed by alpha-particles, uroepithelial cells and their malignant counterparts transformed either by alpha-particles or methylcholanthrine-4, and osteosarcoma cells and their nonmalignant counterparts into which the Rb gene had been introduced were used. Dose response curves for all of these cell lines were obtained by exposure to cesium 137 gamma-rays at a dose-rate of 1.18 Gy/min. RESULTS: There was a dramatic increase in resistance to gamma-rays when H-ras was transfected into rodent intestinal epithelial cells. By contrast, in the case of the three human cell lines used, no consistent or significant change of radiosensitivity occurred when normal cells were transformed to a malignant state by alpha-particles or by a chemical carcinogen. CONCLUSIONS: Experiments involving the introduction of foreign oncogenes to cause tumorigenicity and accompanying radioresistance do not have direct relevance in human tumors. In a number of different instances, the conversion to malignancy by means that more closely reflect what happens in practice (i.e., by radiation or a chemical carcinogen) is not necessarily accompanied by an increased radioresistance to low doses of radiation.

Taxol in combination with acute and low dose rate irradiation.

Taxol is an investigational antineoplastic agent which acts by stabilizing microtubules, thereby preventing normal mitosis. It is believed to block cells in the G2/M phase of the cell cycle. The drug is a natural product isolated from the yew, Taxus brevifolia. We have used a cell line derived from human cervical carcinoma to investigate the combination of Taxol with high and low dose rate 137Cs irradiation. An additive effect for Taxol plus radiation was observed; supra-additivity or synergism is not suggested by our data. In the cell line studied, drug concentrations that accumulate cells to some degree in the G2/M phase of the cycle lead to cell lethality, so that no radiosensitizing effect is possible. We have also shown that the cytotoxic effect of Taxol is not limited to the G2/M phase of the cell cycle. In the clinic, Taxol shows promise both as a chemotherapeutic agent and as a possible adjunct to radiation. The present work demonstrates the need for further studies of Taxol plus radiation with a variety of human cell lines of normal and malignant origin.

Protein deposits on individual hydrophilic contact lenses: effects of water and ionicity.

Chemical procedures have been developed for eluting deposits from individual hydrophilic contact lenses using combinations of solvents. Total protein was determined as a function of the FDA-proposed classification system for hydrogel lenses. Group IV lenses (high water content, ionic matrix polymers) contained the greatest amount of protein deposits, while group I lenses (low water content, non-ionic polymers) contained the least. Group II lenses (high water content, non-ionic polymers) showed an affinity for protein greater than groups I and III (low water content, ionic polymer) but significantly less than group IV. The necessary basic conditions for maximal protein contamination of hydrophilic contact lenses seems to be created through a combination of an ionic polymer existing in a polar, high water content milieu.

Potentially lethal damage repair in cell lines of radioresistant human tumours and normal skin fibroblasts.

Radiation cell survival data were obtained in vitro for three cell lines isolated from human tumours traditionally considered to be radioresistant--two melanomas and one osteosarcoma--as well as from a diploid skin fibroblast cell line. One melanoma cell line was much more radioresistant than the other, while the osteosarcoma and fibroblast cell lines were more radiosensitive than either. For cells growing exponentially, little potentially lethal damage repair (PLDR) could be demonstrated by comparing survival data for cells in which subculture was delayed by 6 h with those sub-cultured immediately after treatment. For the malignant cells in plateau phase, which in these cells might be better termed 'slowed growth phase', since an appreciable fraction of the cells are still cycling, a small amount of PLDR was observed, but not as much as reported by other investigators in the literature. The normal fibroblasts, which achieved a truer plateau phase in terms of noncycling cells, showed a significantly larger amount of PLDR than the tumour cells.