Prognostic indicators for gastrointestinal stromal tumours: a clinicopathological and immunohistochemical study of 108 resected cases of the stomach

AIMS: Whether immunohistochemical markers increase accuracy in predicting prognosis for gastrointestinal stromal tumours (GISTs) remains uncertain. However, past studies have used only small, heterogeneous patient groups. Our aim was to test previously studied and more novel morphological features as well as four immunohistochemical markers as prognostic indicators amongst a large cohort of surgically resected, gastric GISTs. METHODS AND RESULTS: Tissues from 127 gastric mesenchymal tumours were collected retrospectively and subjected to repeat histological assessment and immunophenotyping. Further immunohistochemistry was performed for Ki67, p53, Bcl-2 and cyclin D1. Complete follow-up data were collected for 108 patients with immunophenotyped diagnoses of GIST (i.e. c-kit+ tumours). At the census point, 52 patients were alive, 24 had died from their GISTs and the remainder of other causes. Univariate analysis showed the following predicted for shorter disease-specific survival: size > or =50 mm; necrosis, no intratumoral lymphocytes; mitotic count > or =5/50 high power fields; Ki67 labelling index > or =5%; p53 immunopositivity. Of these variables, multivariate analyses showed only mitotic count and, to a lesser extent, Ki67 labelling to be independent prognostic indicators. CONCLUSIONS: Mitotic count remains the best predictor of outcome following surgical resection of gastric GISTs. Ki67 immunohistochemistry does not provide better prognostication and p53, Bcl-2 and cyclin D1 immunohistochemistry provide no additional prognostication.     

Reaching to ipsilateral or contralateral targets: within-hemisphere visuomotor processing cannot explain hemispatial differences in motor control

Aiming movements made to visual targets on the same side of the body as the reaching hand typically show advantages as compared to aiming movements made to targets on the opposite side of the body midline in the contralateral visual field. These advantages for ipsilateral reaches include shorter reaction time, higher peak velocity, shorter duration and greater endpoint accuracy. It is commonly hypothesized that such advantages are related to the efficiency of intrahemispheric processing, since, for example, a left-sided target would be initially processed in the visual cortex of the right hemisphere and that same hemisphere controls the motor output to the left hand. We tested this hypothesis by examining the kinematics of aiming movements made by 26 right-handed subjects to visual targets briefly presented in either the left or the right visual field. In one block of trials, the subjects aimed their finger directly towards the target; in the other block, subjects were required to aim their movement to the mirror symmetrical position on the opposite side of the fixation light from the target. For the three kinematic measures in which hemispatial differences were obtained (peak velocity, duration and percentage of movement time spent in deceleration), the advantages were related to the side to which the motor response was directed and not to the side where the target was presented. In addition, these effects tended to be larger in the right hand than in the left, particularly for the percentage of the movement time spent in deceleration. The results are interpreted in terms of models of biomechanical constraints on contralateral movements, which are independent of the hemispace of target presentation.     

Premixed rapid-setting calcium phosphate composites for bone repair

Although calcium phosphate cement (CPC) is promising for bone repair, its clinical use requires on site powder-liquid mixing. To shorten surgical time and improve graft properties, it is desirable to develop premixed CPC in which the paste remains stable during storage and hardens only after placement into the defect. The objective of this study was to develop premixed CPC with rapid setting when immersed in a physiological solution. Premixed CPCs were formulated using the following approach: Premixed CPC = CPC powder + nonaqueous liquid + gelling agent + hardening accelerator. Three premixed CPCs were developed: CPC-monocalcium phosphate monohydrate (MCPM), CPC-chitosan, and CPC-tartaric. Setting time for these new premixed CPCs ranged from 5.3 to 7.9 min, significantly faster than 61.7 min for a premixed control CPC reported previously (p < 0.05). SEM revealed the formation of nano-sized needle-like hydroxyapatite crystals after 1 d immersion and crystal growth after 7 d. Diametral tensile strength for premixed CPCs at 7 d ranged from 2.8 to 6.4 MPa, comparable to reported strengths for cancellous bone and sintered porous hydroxyapatite implants. Osteoblast cells attained a normal polygonal morphology on CPC-MCPM and CPC-chitosan with cytoplasmic extensions adhering to the nano-hydroxyapatite crystals. In summary, fast-setting premixed CPCs were developed to avoid the powder-liquid mixing in surgery. The pastes hardened rapidly once immersed in physiological solution and formed hydroxyapatite. The cements had strengths matching those of cancellous bone and sintered porous hydroxyapatite and non-cytotoxicity similar to conventional non-premixed CPC.     

Tuberculous tenosynovitis

Tuberculous tenosynovitis is rare and may be overlooked as a cause of chronic tenosynovitis. This report presents a case of a young woman with tuberculosis tenosynovitis of the wrist, and highlights the clinical, imaging, histological, and laboratory features most commonly seen in this disease.     

Dominantly inherited renal adysplasia

We are reporting on 7 families with both unilateral and bilateral renal agenesis (or severe dysplasia). This condition, termed hereditary renal adysplasia (HRA) [Buchta et al, 1973], is an autosomal dominant trait with incomplete penetrance and variable expression. Review of the literature on familial renal agenesis suggests that HRA is more common than previously supposed and may account for most recurrences of bilateral renal agenesis (BRA), even when the parents are normal. There are no consistent phenotypic differences between sporadic and familial renal agenesis. Associated non-urogenital anomalies, although more frequent in sporadic cases, have been reported in HRA. Use of several approaches, including the Weinberg Proband Method, segregation analysis, and empiric risk estimation, leads to the conclusion that autosomal dominant inheritance is the most likely pattern of transmission for most cases of renal agenesis. Penetrance is between 50% and 90%. Ultrasound study of the kidneys of parents, sibs, and other relatives is recommended in all families in which there is an individual with unilateral or bilateral renal agenesis. The empiric risk for recurrence of BRA in sibs has been estimated at 3.5% [Carter, et al, 1979] but in the offspring of affected or obligate heterozygotes for HRA, the empiric risk of bilateral severe renal adysplasia is 15-20%.     

Association between a complex insertion/deletion polymorphism in NOD1 (CARD4) and susceptibility to inflammatory bowel disease

The identification of the role of genetic variants within NOD2 (CARD15) in Crohn's disease and ulcerative colitis susceptibility highlight the role of the innate immune system in inflammatory bowel disease (IBD) pathogenesis. NOD1 (CARD4) is located on chromosome 7p14.3, in a region of known linkage to IBD and encodes an intracellular bacterial pathogen-associated molecular pattern receptor that is closely related to NOD2. We have identified strong association between haplotypes in the terminal exons of NOD1 and IBD (multi-allelic P = 0.0000003) in a panel of 556 IBD trios. The deletion allele of a complex functional NOD1 indel polymorphism (ND(1) + 32656*1) was significantly associated with early-onset IBD (P = 0.0003) in unrelated cases and controls. ND1 + 32656*1 was also associated with extra-intestinal manifestations of IBD (P = 0.04). These findings in two independent populations provide strong evidence for a role for NOD1 variants in IBD susceptibility and reinforce the role of the innate immune system in IBD pathogenesis.     

Hospitalisations due to falls in older persons

This paper describes hospitalisations due to falls among people aged 65 years and over resident in the Eastern Region of Ireland. Of the 2,029 hospitalisations recorded for 2002, 78% were female and 68% were aged 75 years and over. Fractures accounted for 1,697 or 84% of cases with nearly half of them (841) sustained to the hip. Females were more likely to have a limb fracture whereas males were more likely to have a head injury. The total inpatient costs of the 2,029 hospitalisations were estimated at 10.6 million euros. Hip fractures were the costliest injuries as they accounted for 7.4 million euros (70%) of inpatient costs. There are also substantial additional costs implications for hip fractures as they constituted the majority (56%) of cases transferred to nursing/convalescent homes or long-stay health facilities. In keeping with an ageing population, the problem of injuries in older people is likely to increase over time and as falls are the dominant cause of those injuries, all acute and long-stay health facilities need to develop and implement fall prevention strategies for older people.     

Effect of creatine supplementation on metabolism and performance in humans during intermittent sprint cycling

This double blind study investigated the effect of oral creatine supplementation (CrS) on 4 × 20 s of maximal sprinting on an air-braked cycle ergometer. Each sprint was separated by 20 s of recovery. A group of 16 triathletes [mean age 26.6 (SD 5.1) years. mean body mass 77.0 (SD 5.8) kg, mean body fat 12.9 (SD 4.6)%, maximal oxygen uptake 4.86 (SD 0.7) l · min⁻¹] performed an initial 4 × 20 s trial after a muscle biopsy sample had been taken at rest. The subjects were then matched on their total intramuscular creatine content (TCr) before being randomly assigned to groups to take by mouth either a creatine supplement (CRE) or a placebo (CON) before a second 4 × 20 s trial. A muscle biopsy sample was also taken immediately before this second trial. The CrS of 100 g comprised 4 × 5 g for 5 days. The initial mean TCr were 112.5 (SD 8.7) and 112.5 (SD 10.7) mmol · kg⁻¹ dry mass for CRE and CON, respectively. After creatine loading and placebo ingestion respectively, CRE [128.7 (SD 11.8) mmol · kg⁻¹ dry mass] had a greater (P=0.01) TCr than CON [112.0 (SD 10.0) mmol · kg⁻¹ dry mass]. While the increase in free creatine for CRE was statistically significant (P=0.034), this was not so for the changes in phosphocreatine content [trial 1: 75.7 (SD 6.9), trial 2: 84.7 (SD 11.0) mmol · kg⁻¹ dry mass, P=0.091]. There were no significant differences between CRE and CON for citrate synthase activity (P=0.163). There was a tendency towards improved performance in terms of 1 s peak power (in watts P=0.07; in watts per kilogram P=0.05), 5 s peak power (in watts P=0.08) and fatigue index (P=0.08) after CrS for sprint 1 of the second trial. However, there was no improvement for mean power (in watts P=0.15; in watts per kilogram P=0.1) in sprint 1 or for any performance values in subsequent sprints. Our results suggest that, while CrS elevates the intramuscular stores of free creatine, this does not have an ergogenic effect on 4 × 20 s all-out cycle sprints with intervening 20-s rest periods. Accepted: 2 October 2000