Comparative genomic hybridization (CGH) of augmentation cystoplasties

OBJECTIVE: Tumors arising within augmentation cystoplasties are aggressive, have poor prognosis and the majority are not detected at follow-up cystoscopy. Genetic changes in tumors precede morphological abnormalities. Therefore, the aim of this study was to investigate whether genetic abnormalities detected by comparative genomic hybridization (CGH) could be used to identify those patients with augmentation cystoplasties at increased risk of tumorigenesis. METHODS: Bladder biopsy samples were obtained from 16 augmentation cystoplasty patients both distant from and near to the enterovesical anastomosis. CGH was used to detect genetic abnormalities in DNA extracted from the biopsies, archival specimens of two augmentation cystoplasties and two de novo bladder adenocarcinomas. RESULTS: A greater number of amplifications on 2p, 3q, 8q, 9p, 17p, 18pq and 20pq, were observed in bladder biopsies obtained near to the enterovesical anastomosis compared to those taken distant to the suture line. CGH of archival augmentation cystoplasty tumor DNA indicated abnormalities at several loci with amplifications at 2q, 5q, 10p and 21pq, while deletions occurred at 5p and 16p. CONCLUSIONS: The results of this study suggest that the urothelium adjacent to the bladder and/or bowel anastomosis in augmentation cystoplasties is genetically unstable. Furthermore, longitudinal studies are required to establish whether or not patients exhibiting genetic instability following augmentation cystoplasty are at greater risk of developing tumors than those with genetically stable epithelia.     

How are nations trying to prevent suicide? An analysis of national suicide prevention strategies

Recent increases in suicide rates internationally have focused attention on suicide as an important area of public health concern. In this review, strategies developed by various countries to halt this trend are compared. Nine out of 15 countries respond to enquiry about the state of development of suicide prevention strategies and programmes. Comprehensive strategies have been or are being developed by Finland, Norway, Australia, New Zealand and Sweden. The organization of these strategies differs between countries. The interventions have similar targets and are presented in detail. There are some similarities in strategy content but evident differences in organization. Further developments should not only be based on research, but also consider the diverse experiences of other countries, and they should incorporate appropriate structures for monitoring and evaluation.     

Management of superficial G2 (pTa and pT1) bladder cancer

A total of 143 patients with superficial G2 (pTa, pT1) bladder cancer (48 G2pTa; 95 G2pT1) presenting between 1970 through 1987 were reviewed. Of 48 patients with G2pTa followed for up to eighteen years, G3 recurrence developed only in 1 (2.0%), and invasive cancer (greater than pT2) developed only in 2 (4.2%). They both received radiotherapy and have responded completely. There have been no cancer-related deaths. In contrast, in the 95 patients in whom the basement membrane had been breached (pT1), higher grade tumor (G3) developed in 11 (11.5%), and 15 (16%) had recurrences with invasion of muscle (greater than pT2). Among these there were 7 (7.3%) cancer-related deaths.     

Effects of arginine vasopressin (AVP) infusions on circulating concentrations of platelet AVP, factor VIII: C and von Willebrand factor

To study the possible role of arginine vasopressin (AVP) in the control of haemostasis AVP infusions at 3 doses (0.1, 0.2 and 0.3 mU/kg/min) were performed in 6 male volunteers. Both plasma and platelet AVP concentrations rose in a dose-related manner. At doses of 0.2 and 0.3 mU/kg/min there was an increase in the plasma concentrations of both plasma Factor VIII and von Willebrand factor. The data support the hypothesis that AVP, by interacting with platelets and stimulating factor VIII and von Willebrand factor release, plays a role in the control of haemostasis.     

Traumatic intratemporal facial nerve injury: management rationale for preservation of function

A retrospective review of 29 cases of intratemporal facial nerve injuries included 18 temporal bone fractures, 7 gunshot wounds, and 4 iatrogenic complications. Surgical exploration confirmed involvement of the fallopian canal in the perigeniculate region in 14 longitudinal and 3 transverse or mixed fractures of the petrous pyramid. Gunshot and iatrogenic injuries usually occurred within the tympanic and vertical segments of the facial canal and at the stylomastoid foramen. When hearing is salvageable, the middle fossa approach provides the best access to the perigeniculate region of the facial nerve. In the presence of severe sensorineural hearing loss, the transmastoid-translabyrinthine approach is the most appropriate for total facial nerve exploration. Grade I to III results can be anticipated in timely decompression of lesions caused by edema or intraneural hemorrhage. Undetectable at the time of surgery, stretch and compression injuries with disruption of the endoneural tubules often lead to suboptimal results. Moderate-to-severe dysfunction (Grade IV), with slight weakness and synkinesis, is the outcome to be expected from the use of interpositional grafts.     

Variability in hand surface representations in areas 3b and 1 in adult owl and squirrel monkeys

Detailed microelectrode maps of the hand representation were derived in cortical areas 3b and 1 from a series of normal adult owl and squirrel monkeys. While overlap relationships were maintained, and all maps were internally topographic, many map features varied significantly when examined in detail. Variable features of the hand representations among different monkeys included a) the overall shapes and sizes of hand surface representations; b) the actual and proportional areas of representations of different skin surfaces and the cortical magnifications of representations of specific skin surfaces, which commonly varied severalfold in area 3b and manyfold in area 1; c) the topographic relationships among skin surface representations, with skin surfaces that were represented adjacently in some monkeys represented in locations many hundreds of microns apart in others; d) the internal orderliness of representations; e) the completeness of representations of the dorsal hand surfaces; and f) the skin surfaces represented along the borders of the hand representation. Owl monkey maps were, in general, internally more strictly topographic than squirrel monkey maps. In both species, area 3b was more strictly topographic and less variable than was area 1. The degree of individual variability revealed in these experiments is difficult to reconcile with the hypothesis that details of cortical maps are ontogenetically specified during a period in early life. Instead, we propose that differences in the details of cortical map structure are the consequence of individual differences in lifelong use of the hands. This conclusion is consistent with earlier studies of the consequences of peripheral nerve transection and digital amputation, which revealed that cortical maps are dynamically maintained and are alterable as a function of use or nerve injury in these monkeys (Merzenich et al., '83a,b, '84a; Merzenich, '86; Jenkins et al., '84; Jenkins and Merzenich, '87).     

Central fat predicts deterioration of insulin secretion index and fasting glycaemia: 6-year follow-up of subjects at varying risk of Type 2 diabetes mellitus.

AIMS: To examine the relationships between body composition and changes in fasting glycaemia, and in indices of insulin secretion and insulin action over 6 years in females with a family history of Type 2 diabetes with or without prior gestational diabetes ('at risk' group, AR) and control females (control group, C). METHODS: At baseline and at follow-up, an oral glucose tolerance test and dual energy X-ray absorptiometry assessment of body composition were performed. Indices of insulin resistance (HOMA R') and insulin secretion (HOMA beta') were obtained from fasting insulin and glucose concentrations. RESULTS: At baseline, the groups were similar for age, body mass index, fasting levels of plasma glucose and insulin, HOMA R' and HOMA beta'. Despite similar total body fatness, AR had significantly greater waist circumference and central fat (both P < 0.02) compared with C. At follow-up there was a significant increase in central adiposity only in AR, and the fasting plasma glucose (FPG) level was higher in AR compared with C (5.0 +/- 0.2 vs. 4.3 +/- 0.2 mmol/l, P = 0.02). This rise in plasma glucose in AR was related to a decline in HOMA beta' (r = 0.45, P = 0.0065). Both the baseline and the increments in total and central abdominal fat mass were associated with the time-related decline in HOMA beta'. CONCLUSIONS: Six years after initial assessment, AR showed deterioration in FPG levels due predominantly to a decline in insulin secretion index without major change in insulin resistance index. Importantly, baseline body fatness (especially central adiposity), as well as increases in fatness with time, were the major predictors of the subsequent decline of insulin secretion index and the consequent rise in FPG.