p53 Accumulation Is a Prognostic Factor in Intestinal-Type Gastric Carcinoma but Not in the Diffuse Type

Background: The prognostic value of p53 nuclear accumulation in gastric cancer is still unclear, as shown by the discordant results still reported in the literature. In this study, we evaluated the correlation between p53 accumulation and long-term survival of patients resected for intestinal and diffuse-type gastric cancer.Methods: Eighty-three patients with carcinoma of the intestinal type and 53 patients with carcinoma of the diffuse type were included in the study. Immunohistochemical staining of the paraffin sections was performed by using monoclonal antibody DO1; cases were considered positive when nuclear immunostaining was observed in 10% or more of the tumor cells. Prognostic significance of different variables was investigated by univariate and multivariate analysis.Results: p53 positivity was found in 51.8% of intestinal-type and 50.9% of diffuse-type cases. No significant correlation between the rate of p53 overexpression and age, sex, tumor location, tumor size, depth of invasion, lymph node involvement, distant metastases, and surgical radicality was found in the two groups of patients. A statistically significant difference in survival rate was observed between p53-negative and p53-positive cases in the intestinal type (P < .05), confirmed by multivariate analysis (P < .005; relative risk = 3.09). On the contrary, no correlation with survival was found in diffuse-type cases according to p53 overexpression.Conclusions: These results suggest that the immunohistochemical detection of p53 accumulation is a useful indicator of poor prognosis in the intestinal but not in the diffuse type of gastric cancer, and are indicative of distinct molecular pathways and pattern of progression in the two histotypes.     

Risk factors for rape, physical assault, and posttraumatic stress disorder in women: examination of differential multivariate relationships

The National Women's Study, a 2-year, three-wave longitudinal investigation, employed a national probability sample of 3,006 adult women to: (a) identify separate risk factors for rape and physical assault, and (b) identify separate risk factors associated with post-rape posttraumatic stress disorder (PTSD) and post-physical assault PTSD. This investigation differed from previous studies in that it prospectively examined risk factors at the multivariate, as opposed to univariate level. Overall, past victimization, young age, and a diagnosis of active PTSD increased women's risk of being raped. By contrast, past victimization, minority ethnic status, active depression, and drug use were associated with increased risk of being physically assaulted. Risk factors for PTSD following rape included a history of depression, alcohol abuse, or experienced injury during the rape. However, risk factors for PTSD following physical assault included only a history of depression and lower education.     

Hypothesis: is low prenatal vitamin D a risk-modifying factor for schizophrenia?

The central nervous system is increasingly being recognised as a target organ for vitamin D via its wide-ranging steroid hormonal effects and via the induction of various proteins such as nerve growth factor. This paper proposes that low maternal vitamin D may impact adversely on the developing foetal brain, leaving the affected offspring at increased risk of adult-onset schizophrenia. The hypothesis can parsimoniously explain diverse epidemiological features of schizophrenia, such as the excess of winter births, increased rates of schizophrenia in dark-skinned migrants to cold climates, the increased rate of schizophrenia births in urban versus rural setting, and the association between prenatal famine and schizophrenia. Studies that will allow rejection of the hypothesis are proposed.     

Potentiation of glutamatergic agonist-induced inositol phosphate formation by basic fibroblast growth factor is related to developmental features in hippocampal cultures: neuronal survival and glial cell proliferation

We investigated the modulation by growth factors of phospholipase C (PLC)-linked glutamate receptors during in vitro development of hippocampal cultures. In defined medium, glial cells represent between 3 and 14% of total cell number. When we added basic fibroblast growth factor (bFGF) 2 h after plating, we found: (i) a neuroprotection from naturally occurring death for up to 5 days; (ii) a proliferation of glial cells from day 3; and (iii) a potentiation of quisqualate (QA)-induced inositol phosphate (IP) formation from 1 to 10 days in vitro (DIV) and 1S, 3R-amino-cyclopentane-1,3-dicarboxylate (ACPD) response from 3 to 10 DIV. The antimitotic cytosine-beta,D-arabinofuranoside (AraC) blocked glial cell proliferation induced by bFGF, but not neuroprotection. Under these conditions, the early potentiation of the QA response (1-3 DIV) was not changed, while the ACPD and late QA response potentiations were prevented (5-10 DIV). Epidermal growth factor was not neuroprotective but it induced both glial cell proliferation and late QA or ACPD potentiation. Surprisingly, the early bFGF-potentiated QA-induced IP response was blocked by 6, 7-dinitro-quinoxaline-2,3-dione (DNQX), suggesting the participation of ionotropic (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate (KA) receptors. The delayed bFGF-potentiated ACPD-induced IP response is inhibited by (S)-alpha-methyl-4-carboxyphenylglycine (MCPG), indicating possible activation of glial metabotropic receptors. These results suggest that, in hippocampal cultures, bFGF modulates AMPA and metabotropic glutamate receptors linked to the IP cascade, possibly in relation to the regulation of neuronal survival and glial cell proliferation, respectively.     

A study on the role of the family and other risk factors in HCV transmission

Background/aims: To understand the intrafamilial transmission and the existing risk factors related to HCV infection in subjects confirmed anti-HCV positive, their sexual partners and household contacts in Friuli, North-East Italy. Methods: We enrolled all the subjects that were consecutively identified as HCV positive during routine laboratory testing in six health districts and their household contacts. From each subject we obtained a blood sample, demographic data and a medical history including the existence of risk factors for HCV. Antibodies to HCV were detected employing a commercially available second-generation enzyme immunoassay (EIA); positive serum specimens were retested using a second-generation recombinant immunoblot assay (RIBA-2). Results: We recruited 743 subjects, 229 first subjects identified as HCV positive and 514 household contacts. There were no statistically significant differences in positivity among household contacts. Analysing intracouple transmission we found no significant differences by gender in couples both with and without parenteral risk factors. We found, both with univariate and multivariate analysis, as statistically significant risk factors in all the subjects: age older than 60, blood transfusions (particularly those performed before 1984), surgical procedures such as abortion and/or uterine curettage, history of HBV infection, intravenous drug use, and tattooing. Conclusions: Our results stress the low relevance of sexual transmission in the intrafamilial context, the importance of abortion and/or uterine curettage, the important role of blood transfusions in the past, a higher prevalence of HCV infection within a household of a HCV positive member compared to all other existing data in the area.     

Assisted suicide and its implications for occupational therapy

Many people's lives have been extended by the miracles of modern medicine and technology. However, although the use of these new technologies and drugs may keep people alive longer, the question arises about the quality of that extended life. This paper reviews one physician's apparent preoccupation with assisted suicide in order to introduce the controversy regarding the ethical, moral and legal implications of physician-assisted suicide in the USA. We discuss the arguments in favour of and against assisted suicide in the context of quality of life, individual autonomy versus communal responsibility, and professional autonomy. Occupational therapy, in particular, may be ethically challenged since one can argue that its aim is to help people lead a meaningful and purposeful life despite severe performance deficits. Copyright © 1999 Whurr Publishers Ltd.     

The a- and b-wave latencies as a prognostic indicator of neovascularisation in central retinal vein occlusion

To evaluate the prognostic value of ERG in cases of central retinal vein occlusion (CRVO) regarding the development of neovascularisation (NV), we studied 20 patients with unilateral CRVO. Half of them were allocated in the perfused group and the other 10 finally developed NV and were allocated in the non-perfused group. Flash ERG was recorded from all patients. Our findings suggest that b-wave latency is the most reliable parameter in predicting NV, followed by the a-wave latency. The b/a wave amplitude of ERG ratio does not seem to be suitable for clinical use. This revised version was published online in July 2006 with corrections to the Cover Date.     

How often is extracorporeal membrane oxygenation needed in cases of congenital diaphragmatic hernia?

Some newborns with congenital diaphragmatic hernia (CDH) and severe pulmonary hypertension cannot be saved by conventional treatment and may obtain some benefit from extracorporeal membrane oxygenation (ECMO) as a bridging measure until adequate hematosis is possible. Early prediction of the insufficiency of optimal assistance is still unclear; we reviewed our recent experience with CDH patients in an attempt to evaluate the real need for ECMO in our institution. Between 1987 and 1994, 47 newborns with CDH manifested in the first 24 h were treated with maximal ventilatory assistance (including high-frequency ventilation in 12 cases) and vasoactive drugs prior to surgical repair. In order to summarize the ventilatory and blood-gas parameters, we determined oxygenation index (OI) and ventilatory index (VI) and compared the results in survivors and nonsurvivors. Overall survival was 60% (2 cases of Fryns' syndrome were excluded from analysis). OI was 10.3±5.7 (mean ± SD) for survivors and 46.2 ± 37.8 for nonsurvivors (P < 0.01). VI was 460.9±303 and 1,532±500.6, respectively (P <0.01). Bayesian analysis and receiver operating characteristic curves enabled us to select a threshold value of OI of 20 as the best means of predicting survival in our current conditions (sensitivity: 0.7, specificity: 0.83). The generally accepted figure of 40 had a sensitivity of 1 but a specificity of only 0.44. For VI, the best threshold value was 1,100 (sensitivity: 0.93, specificity: 0.94), whereas the generally used figure of 1,000 had 0.89 and 1, respectively. According to our results, with our current management conditions, approximately 50% of our CDH patients might have obtained some benefit from ECMO.     

Long-term lowering of blood pressure after carotid and vertebrobasilar ischemic stroke

We followed up 107 patients experiencing a first-ever ischemic stroke after having been affected by essential hypertension for at least one year, in order to analyze the phenomenon of post-stroke blood pressure lowering. Of the 82 patients still surviving after three months of follow-up, 44 (54%) had normal arterial blood pressure values. There were no significant differences between these normotensive patients and the 38 with high blood pressure in terms of cerebrovascular risk factors or disability, but blood pressure normalized in 34 of the 54 patients experiencing a carotid stroke (63%) and in only 10 of the 28 experiencing vertebrobasilar stroke (36%) (p=0.035). These data may offer a starting point for further studies of the neurogenesis of arterial hypertension.

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Sommario Al fine di analizzare il fenomeno della normalizzazione della pressione arteriosa dopo ictus cerebrale in pazienti prima ipertesi, abbiamo osservato 107 soggetti con primo ictus ischemico, che erano già precedentemente affetti da ipertensione arteriosa da almeno un anno. Degli 82 (77%) sopravvissuti a tre mesi di follow-up, 44 (54%) hanno mostrato una normalizzazione della pressione arteriosa. L'incidenza di fattori di rischio per malattia cerebrovascolare e disabilità grave non è risultata significativamente diversa nel gruppo degli ipertesi rispetto ai normotesi. Tuttavia la normalizzazione della pressione arteriosa è stata osservata in 34 dei 54 pazienti con ictus carotideo (63%) e solo in 10 dei 28 con ictus vertebrobasilare (36%) (p=0.035). Riteniamo che tali dati offrano uno spunto per ulteriori ricerche sulla genesi neurogena dell'ipertensione arteriosa essenziale.

     

Cerebellar astrocytomas in children

Cerebellar astrocytomas, as a group, carry a more favorable prognosis than most other brain tumors, because these neoplasms generally are histologically benign and amenable to extensive resection. However, it is clear that a number of factors have an impact on prognosis. In particular, resection extent has been strongly associated with progression-free survival: patients undergoing gross total resection appear to have a substantially better prognosis than those undergoing incomplete resection. Brainstem invasion, which is the factor that most often precludes a complete resection, has also been associated with a less favorable prognosis. In addition, histological features indicative of malignancy are clearly associated with a poor outcome.In contrast to the above observations, which have been established convincingly in the literature, a number of issues regarding cerebellar astrocytomas remain unresolved. First, the correlation between histology and prognosis among patients with low-grade cerebellar astrocytomas is uncertain: in some series, pilocytic astrocytomas have been associated with a better prognosis than non-pilocytic tumors, but in other studies, no such relationship has been observed. Second, the role of radiotherapy after incomplete resection of a low-grade cerebellar astrocytoma remains problematic. In view of the lack of convincing data in this regard, many groups, including our own, defer radiotherapy until there is evidence of progressive disease that is surgically unresectable. Finally, the frequency of follow-up in patients with cerebellar astrocytomas remains largely empirical. Although most recurrences are detected within a few years after initial surgery, late recurrences are well known, which raises the question of when and if such patients should be regarded as cured of their disease. Long-term multi-institutional natural history studies are in progress to address the above issues.