Franco Pacini

General and cancer specific mortality of a population based cohort of patients with inflammatory bowel disease: the Florence study

Background—A population based epidemiological study identified all the patients diagnosed with ulcerative colitis (UC) or Crohn’s disease (CD) resident in the Florence area in the period 1978–1992. Aims—To assess the mortality of unselected patients with inflammatory bowel disease (IBD) in a Mediterranean country. Methods—Overall, 920 patients (689 UC and 231 CD) were followed until death or end of follow up (31 December 1996). Information on vital status was available for all except eight patients (0.9%); 70 deaths were identified (23 in patients with CD and 47 in patients with UC). Expected deaths were estimated on the basis of five year age group, gender, and calendar year national mortality rates. Standardised mortality ratios (SMR) and 95% confidence intervals were calculated. Results—General mortality was significantly lower than expected in UC (SMR 0.6; 95% confidence interval 0.4 to 0.8), due to a reduced number of cardiovascular and, possibly, smoking related deaths. Cancers of the respiratory tract were significantly reduced in UC but tended to be increased in patients with CD. These latter patients had not only an increased cancer mortality but also a 40% increased risk of dying for all causes already evident in the first five year follow up period and persisting thereafter. In contrast, in patients with UC, SMRs were initially very low but tended to increase steadily over the follow up period. Gastrointestinal deaths were particularly increased in patients with CD, but only moderately in those with UC. Overall, there was some evidence of a twofold increased mortality for colorectal cancer, the risk being highest for rectal cancers in patients with UC. A non-significant excess of deaths due to haemolymphopoietic malignancies and suicides was also observed. Conclusions—This study, the first in a Mediterranean country, supports the existence of two divergent mortality patterns for patients with UC and CD, possibly explained by differences in smoking habits and by a greater severity of CD.

Intermittent therapy with high-dose 5-aminosalicylic acid enemas for maintaining remission in ulcerative proctosigmoiditis

Sixty patients who had presented recently with a relapse of mild to moderate ulcerative colitis with rectosigmoid involvement were randomly assigned to treatment with either 5-aminosalicylic acid enemas (N=29) or oral sulfasalazine (N=31). All patients were in remission, which was documented by clinical, histologic, and endoscopic criteria. Five-aminosalicylic acid treatment was administered on an intermittent schedule, consisting of 4 gm daily for the first seven days of each month; sulfasalazine was given as continuous therapy (2 gm daily as oral tablets). The study period was 2 years. Overall, 9 relapses occurred in the 5-aminosalicylic acid group and 12 occurred in the sulfasalazine group. The actuarial relapse rate at 12 months was 20 percent in the 5-aminosalicylic acid group and 24 percent in the sulfasalazine group; at 24 months, these rates were 37 and 43 percent, respectively. The actuarial relapse curves of the two groups were very similar. The relapse severity was also similar between the two groups. These results show that the authors proposed schedule of maintenance treatment with high-dose 5-aminosalicylic acid enemas is effective in subjects with rectosigmoiditis. This form of intermittent therapy may therefore be proposed for maintaining remission in patients who are refractory to oral and/or rectal treatment with sulfasalazine and steroids or who are intolerant or allergic to sulfasalazine. Treatment with 5-aminosalicylic acid enemas for seven days each month can also constitute an alternative for patients who favor the intermittent schedule over the classic continuous regimen of oral administrations.

Susceptibility to Refractory Ulcerative Colitis Is Associated with Polymorphism in the hMLH1 Mismatch Repair Gene

The hMLH1 gene lies in the linkage susceptibility region to inflammatory bowel disease (IBD) on 3p21. A single nucleotide polymorphism, 655A>G, in exon 8 of the gene causes an I219V change in the MLH1 protein. To test whether hMLH1 may confer susceptibility to ulcerative colitis (UC), we investigated an association between the 655A>G polymorphism and the disease. DNA-based technologies were used to analyze the 655A>G polymorphism in 201 UC patients and 126 healthy ethnically matched controls. The comparison of the allelic frequencies of the 655A>G polymorphism in UC patients and healthy controls did not show significant differences. However, genotype frequencies at the hMLH1 655 position were found to be significantly different when patients with and without refractory UC were compared. This was mainly attributable to a higher level of homozygosity for the G allele in refractory UC patients. Almost 5 times as many (4.9 times) refractory UC patients carried the GG genotype compared with nonrefractory patients (P < 0.0001). The present study provides evidence that the hMLH1 gene is involved in genetic susceptibility to refractory UC. If confirmed by other studies, the GG genotype at position 655 of the hMLH1 gene may represent a useful predictive factor for the clinical management of UC patients.

Neutron Stars in Supernova Remnants

I briefly summarize some facts and ideas concerning the presence of neutron stars in Supernova remnants. While sources similar to the Crab Nebula require the presence of a central energetic object, shell-type remnants such as Cas A are compatible with the presence of neutron stars releasing a weak relativistic wind.

Genetic and inflammatory bowel disease (IBD): is there a relationship between polymorhism of hMLH1 gene and different subtype of ulcerative colitis (UC)?

Genetic and inflammatory bowel disease (IBD): is there a relationship between polymorhism of hMLH1 gene and different subtype of ulcerative colitis (UC)?

Some Problems in the Theory of Isolated Pulsars

In this lecture I will briefly summarize some of the many problems which have confronted (or still puzzle) theorists since the discovery of pulsars, more than 20 years ago. I refer the reader interested in this subject to a recent paper by Srinivasan (1989), to a review by Ruderman (1987) and to the references contained in them. My main topics will be: n n1. n nthe magnetospheric model: basic theory versus real life. n n n n n2. n nthe radiation process, including the implications of the possible recent detection of the ( mathop{e}limits^{ - } - mathop{e}limits^{ + } ) annihilation line from the Crab pulsar. n n n n n3. n nrelativistic winds and plerionic SN Remnants.

High energy phenomena in the supernova 1987A and its hypothetical central pulsar

The presence of a substantial flux of hard X-rays (≳ 20 KeV) from SN 1987 A has been widely interpreted as due to down-compotonization of nuclear gamma ray lines from Co56 taking place in the expanding envelope. This is supported by the parallel detection of the nuclear lines and by the fact that the hard X-rays have started to decay in the Fall of 1988, as expected. n nThe presence and persistence of a softer X-ray flux in the range 6–20 KeV cannot be interpreted along the same lines and can perhaps be ascribed to non-thermal radiation from a central pulsar-powered nebula. We will discuss the requirements and expectations of this model, as well as the significance of the 0.5 millisecond optical pulsar which has been recently reported to exist in SN 1987 A.