Characterization of the major susceptibility region for psoriasis at chromosome 6p21.3.

Psoriasis is a common inflammatory skin condition caused by genetic and environmental factors. Recent genome-wide linkage analyses have identified a locus encoding susceptibility to psoriasis and placed this gene in the 12 cM interval between markers D6S426 and D6S276 on chromosome 6p21.3. This is a broad region and encompasses the human major histocompatibility complex. We have sought to localize the susceptibility gene more precisely by exploiting the linkage, haplotype, and linkage disequilibrium information available through genotyping 118 affected sib pairs, their parents and other affected family members. A total of 14 highly polymorphic markers were genotyped, combining anonymous loci with the class I genes HLA-B and -C distributed across a genetic interval of approximately 14 cM including the entire major histocompatibility complex. Through the application of higher density mapping within the major histocompatibility complex, we identified those regions most commonly shared identical by descent in patients with psoriasis. Using the transmission-disequilibrium test, we found significant evidence of linkage and allelic association across an interval defined by the markers tn62 (p = 1.0 x 10(-7)), HLA-B (p = 4.0 x 10(-7)), and HLA-C (p = 2.7 x 10(-9)), a region encompassed within a 285 kb genomic DNA fragment. Hence these studies contribute to the refinement of the localization of a major psoriasis susceptibility gene and place the critical region near to HLA-C.     

Changing role for preoperative embolisation in the management of arteriovenous malformations of the brain

BACKGROUND: The aim of this study was to analyse the results of the use of preoperative embolisation in the management of arteriovenous malformations of the brain at one institution between 1989 and 1999. METHODS: Two hundred and fifty consecutive cases of angiographically confirmed arteriovenous malformations underwent surgery by one surgeon. Cases of dural or spinal arteriovenous malformations have been excluded. Forty-five cases underwent preoperative embolisation. Embolisation was mostly by particulate embolic material delivered 4 to 6 days before the intended surgery. The incidence of embolisation declined from 21 cases of the first 50 arteriovenous malformation cases surgically treated to five in the last 50 cases. For arteriovenous malformations of less than 3 cm, only the first two temporal quintiles had embolised cases; six in the first and three in the second. Outcome was measured by the Modified Rankin Scale. RESULTS: By 12 months (or last follow up, if less than this time has elapsed) following surgery, 1.6% of patients had died, 2.4% had a Modified Rankin scale score of 4 or 5, 6.4% had a Modified Rankin scale score of 3, 8.4% had a Modified Rankin scale score of 2, 14.4% had a Modified Rankin scale score of 1, and 66.8% were without neurological deficit. There was no difference in outcomes in each of the temporal quintiles. The four deaths were related to intraoperative haemorrhage, ruptured aneurysm, acute myocardial infarction or unrelated infection. Angiographic cure was achieved in 244 of 246 surviving cases. The two cases with residual arteriovenous malformations underwent focussed irradiation. Permanent morbidity could be attributable to embolisation, intraoperative events (resection functional brain, arteriovenous malformation rupture, aneurysm rupture or myocardial infarction) or postoperative events (arterio-capillary-venous hypertensive syndrome or infection). Of these 29 patients 14 had undergone embolisation. Mortality and major morbidity (Modified Rankin scale score greater than 2 due to treatment) occurred in 8.8% undergoing embolisation compared with 1.9% not embolised. The cause for major morbidity in these four embolised cases was intraoperative or postoperative haemorrhage. CONCLUSIONS: These results reflect that cases selected for embolisation were those at most risk from intraoperative haemorrhage. Arteriovenous malformations that are less than 3 cm in maximal diameter should only rarely be considered for preoperative embolisation because of their low surgical morbidity. In the presence of a significant deep perforating artery contribution that cannot be effectively embolised the risks of operative haemorrhage is high irrespective of the effectiveness of embolising ancillary non-perforating arteries.     

The diagnostic yield of intravenous urography.

BACKGROUND: Intravenous urography (IVU) is considered an integral imaging component of the nephro-urological work-up in a wide array of clinical settings. At our institution there is an open-access policy with regard to requesting IVU studies. METHODS: In a prospective, blinded observational study we undertook to assess the diagnostic yield of IVU with respect to the source of referral (i.e. Urology, Nephrology, GP, A & E, other speciality) and the presenting features, such as renal colic, haematuria, bladder outflow obstruction, recurrent urinary tract infection (UTI) etc. Two hundred consecutive patients were evaluated. RESULTS: Overall, 23% of tests were positive. There was a highly significant difference in diagnostic yield between the groups (P<0.001 for both referral source and test indication). A positive result was most likely after referral by a kidney specialist (37.1%) and when the test indication was renal colic (42%) or haematuria (32%). The yield was <15% in all other circumstances, with 94.9% and 92.1% of GP- and other hospital speciality-initiated IVUs being negative. When investigating recurrent UTI, 91.7% of tests were negative and 86.2% were negative when the indication was bladder outflow obstruction. CONCLUSIONS: It is suggested that an open access policy for IVU is not justified, especially when cost and the risk associated with contrast media and radiation exposure are taken into account. Our study supports the abandonment of routine IVU in the investigation of UTI and bladder outflow obstruction.     

Chronic toxicity and hazard assessment of an inorganic mixture simulating irrigation drainwater to razorback sucker and bonytail

We conducted two 90 day chronic toxicity studies with two endangered fish, razorback sucker and bonytail. Swim‐up larvae were exposed in a reconstituted water simulating the middle Green River. The toxicant mixture simulated the environmental ratio and concentrations of inorganics reported in a Department of the Interior study for the mouth of Ashley Creek on the Green River, and was composed of nine elements. The mixture was tested at 1X, 2X, 4X, 8X, and 16X where X was the measured environmental concentration (2 μg/L arsenic, 630 μg/L boron, 10 μg/L copper, 5 μg/L molybdenum, 51 μg/L selenate, 8 μg/L selenite, 33 μg/L uranium, 2 μg/L vanadium, and 20 μg/L zinc). Razorback sucker had reduced survival after 60 days exposure to the inorganic mixture at 8X, whereas growth was reduced after 30 and 60 days at 2X and after 90 days at 4X. Bonytail had reduced survival after 30 days exposure at 16X, whereas growth was reduced after 30, 60, and 90 days at 8X. Swimming performance of razorback sucker and bonytail were reduced after 60 and 90 days of exposure at 8X. Whole‐body residues of copper, selenium, and zinc increased in a concentration‐response manner and seemed to be regulated at 90 days of exposure at 4X and lower treatments for razorback sucker, and at 8X and lower for bonytail. Adverse effects occurred in fish with whole‐body residues of copper, selenium, and zinc similar to those causing similar effects in other fish species. Comparison of adverse effect concentrations with measured environmental concentrations showed a high hazard to the two endangered fish. Irrigation activities may be a contributing factor to the decline of these endangered fishes in the middle Green River. ©2000 John Wiley & Sons, Inc. Environ Toxicol 15: 48–64, 2000     

Risks of brain tumour following treatment for cancer in childhood: Modification by genetic factors,radiotherapy and chemotherapy

A cohort of 4,400 persons treated for various cancers of childhood in France and the UK was followed up over an extended period to assess risks of subsequent brain tumour in relation to the radiotherapy and chemotherapy that the children received for their first cancer. Elevated risks of subsequent brain tumours were associated with first central nervous system (CNS) tumour (two-sided p =0.0002) and neurofibromatosis (two-sided p =0.001). There was also elevated brain tumour risk (two-sided p =0.003) associated with ionising radiation exposure, the risk being concentrated among benign and unspecified brain tumours. The radiation-related risk of benign and unspecified brain tumours was significantly higher than that of malignant brain tumours (two-sided p≤ 0.05); there was no significant change of malignant brain tumour risk with ionising radiation dose (two-sided p > 0.2). In general, there were no strong associations between alkylating agent dose and brain tumour risk. The only significant association between brain tumour risk and alkylating agent dose was in relation to compounds used (bleomycin, chloraminophen) that are thought not to deliver substantial doses to the brain; the statistical significance of the trend with dose depended on a single case, and thus must be considered a weak result. Int. J. Cancer 78:269–275, 1998. Published 1998 Wiley-Liss, Inc.     

Relationship of physical performance to maturation in perimenarchal girls

The relationship of physical performance to maturation, characterized by the onset of menarche, was examined annually from 1989 to 1992 among 61 healthy, active perimenarchal girls from 10 to 14 years. Within each age group, differences in selected physical performance variables between and among three maturity groups, early, average, and late, were compared. Subjects categorized as having early or late maturation were those whose age at menarche was minus or plus, respectively, one standard deviation from the mean age at menarche 12.70 + 0.99 yr (range 10.29–14.65). Subjects demonstrated steady progression with age in breast and pubic hair development. Weight, estimated lean body weight and fat weights, and stature increased significantly with age and maturation. With the exceptions of flexibility, bent arm hang, standing vertical jump, and relative maximum oxygen uptake, the performance measures of running speed, functional strength, explosive strength, static strength, upper body power, and aerobic power improved significantly with age and maturation. Generally more mature subjects tended to perform significantly better than the less mature, but there are fewer significant performance differences between and among maturation groups within specific age groups. Therefore, whereas more mature 10- and 14-year-old females may, within the same age group, have only a very slight advantage in some physical performance abilities over their less mature age mates, more mature females aged 11, 12, and 13 years have a greater physical performance advantage. Am. J. Hum. Biol. 9:163–171, 1997. © 1997 Wiley-Liss, Inc.