Rising incidence of type 1 diabetes in Scottish children, 1984-93. The Scottish Study Group for the Care of Young Diabetics

OBJECTIVES: To calculate the incidence of type 1 diabetes in Scottish children aged less than 15 years between 1984 and 1993; to examine changes in incidence; and to calculate the prevalence of diabetes at the end of this period. DESIGN: Three data sources were used to construct the Scottish Study Group for the Care of Young Diabetics register: active reporting of all new cases; reports from the Scottish Morbidity Register 1; and local registers. SUBJECTS: All children resident in Scotland diagnosed with primary insulin dependent diabetes mellitus when less than 15 years of age between 1984 and 1993. MAIN OUTCOME MEASURES: Annual incidence and prevalence rate for Scotland; time trend in incidence over the 10 years; differences in incidence between the three different age groups; and completeness of the register. RESULTS: The average annual incidence for Scotland was 23.9/100,000 children. The prevalence rate was 1.5/1000 in 1993. A total of 2326 cases was identified from the three sources. Capture-recapture analysis suggests a case ascertainment of 98.6%. The annual incidence rates increased at a rate of 2% each year (rate ratio = 1.02, 95% confidence interval (CI) 1.01 to 1.03). The incidence was higher in boys than girls (rate ratio = 1.08, 95% CI 1.00 to 1.18), and the incidence rates increased with age: 15.3/100,000/year for age 0-4 years, 24.4/ 100,000/year for age 5-9 years, and 31.9/ 100,000/year for age 10-14 years. CONCLUSIONS: The incidence of type 1 diabetes in Scotland is increasing and the prevalence is relatively high. These findings have important implications for health service resource allocation. The Scottish Study Group for the Care of Young Diabetics' register provides a base for monitoring and research.     

Analyses of mutation and loss of heterozygosity of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human gastric cancer

Mutations in the transforming growth factor beta type II receptor (TGFbetaRII) gene have been detected in several human cancer types exhibiting microsatellite instability. Using intron primers previously reported for examination of the entire coding region of the TGFbetaRII gene, 29 sporadic gastric cancers were screened with non-radioactive single strand conformation polymorphism and subsequent DNA sequencing analysis. Mutations of the TGFbetaRII gene were detected in three out of 29 tumors (10%). Two cases showed deletions in a polyadenine tract in both alleles and was positively associated with replication error. One case had an insertion of GA dinucleotide sequence in one allele. Mutations of the TGFbetaRII gene were restricted to exon 3 and other coding regions were not affected. Loss of heterozygosity was detected by analyzing a polymorphic site in intron 2. Three out of nine (33%) informative cases, which were all of intestinal type and advanced cases, showed loss of heterozygosity but neither TGFbetaRII mutation nor replication error was found in these cases. Immunoreactivity of TGFbetaRII in tumor tissues was reduced to a different extent in the gastric cancer with genetically abnormal transforming growth factor. Although the numbers studied are small, homozygous (A)10 deletion or loss of heterozygosity of TGFbetaRII is involved in tumorigenesis and progression of at least some part of sporadic gastric cancer.      

Toxic cardiogenic shock in a patient receiving weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin

A 54-year-old man was treated with weekly 24-h infusion of high-dose 5-fluorouracil (2600 mg/m2) and leucovorin (100 mg/m2) for metastatic colon cancer. At first, he tolerated the treatment well and no significant toxicity was identified. After a total of eight courses of treatment, a stable disease was observed, but mild shortness of breath was found on occasion. The patient had no previous history of cardiac disease and the heart performance assessed by left ventricular ejection fraction before treatment was normal. Unfortunately, acute pulmonary edema with lethal cardiogenic shock occurred during the ninth course of treatment, in spite of intensive medical treatment. The chest X-ray showed extreme cardiomegaly. Repeated assessment of his heart function by echocardiogram and ventricular ejection fraction revealed a very poor cardiac performance. Toxic cardiogenic shock during weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin is extremely rare. To the best of our knowledge, no case has been reported in the English literature. We report a case and the relevant literature about the incidence, clinical picture and possible pathophysiology on 5-fluorouracil-related cardioxicity is reviewed.      

Correlation between basic fibroblast growth factor immunostaining of stromal cells and stromelysin-3 mRNA expression in human breast carcinoma.

We examined the localization of basic fibroblast growth factor (bFGF) in a series of human breast carcinomas using immunohistochemistry. Staining was observed in tumour cells in 15 out of 54 (28%) tumours and in the adjacent stroma in 34 out of 54 (63%) tumours examined. No correlation was observed between positive staining of these two compartments. The relationship between bFGF staining and expression of the metalloprotease stromelysin-3, and between bFGF and microvessel density, was examined. A statistically significant correlation (P < 0.003) was observed between bFGF staining of the stromal compartment and high expression of stromelysin-3 (ST-3; MMP-11) metalloprotease mRNA by stromal cells. In contrast, no correlation was observed between bFGF and intratumour microvessel density (IMD). These results raise the possibility that bFGF may be involved in the induction of stromelysin-3 mRNA expression in breast cancer stroma.     

术前口服依他昔布对妇科手术后病人自控镇痛的影响

目的:观察妇科开腹手术患者术前给予依他昔布120mg对术后自控镇痛(PCA)吗啡用量的影响及其副作用。方法:随机选取全麻下接受妇科开腹全子宫(双附件)切除患者40例,术前分别给予安慰剂或依他昔布120mg口服。在手术后观察24h患者PCA吗啡用量,同时记录患者的疼痛评分和满意度评分,并观察不良反应。结果:术后PCA吗啡24h消耗量在依他昔布组为9.4±7.6mg,显著低于安慰剂组15.7±8.9mg。两组患者24h内对PCA的按压次数依他昔布组也低于安慰剂组(P<0.05)。其中术后3、6、8和12hPCA吗啡消耗量在两组间无显著差异。两组患者术后24h疼痛评分和对镇痛治疗的满意度也无差异。两组患者不良反应的发生率亦无差别。结论:在妇科开腹手术患者术前应用依他昔布120mg可使患者术后PCA吗啡消耗量降低,且在术后12h后下降明显。未发现与依他昔布应用相关的副作用。     

Effects of phencyclidine on acoustic startle and prepulse inhibition in neuronal nitric oxide synthase deficient mice.

Prepulse inhibition of acoustic startle is a behavioural response, which is used to estimate sensorimotor gating deficits in schizophrenia. Recent studies show that several behavioural effects of the psychotomimetic drug, phencyclidine (PCP), in rodents are blocked by nitric oxide synthase (NOS) inhibitors suggesting that NO plays an important role in the pharmacological effects of PCP. The present study was conducted to examine the effects of PCP on prepulse inhibition in neuronal NOS (nNOS) deficient mice. PCP treatment caused a significant and dose-related increase in prepulse inhibition in nNOS-/- mice whereas prepulse inhibition was not significantly affected in +/+ and +/- mice. Basal prepulse inhibition level did not differ significantly between the groups. Furthermore, PCP caused a dose-related decrease in startle response reactivity in +/+ mice but did not significantly affect this measure in +/- and -/- mice. Basal startle response level did not differ between +/+ and +/- but was significantly lower in -/- mice. It is concluded that nNOS plays a role in the NO-sensitive effects of PCP.     

Survival for rectal cancer patients and international comparisons.

BACKGROUND: Population-based cancer registry data are important because they reflect routine care, present long-term follow-up, can show differences in treatment, outcomes and health care over time, and can be used for comparisons between regions and countries. PATIENTS AND METHODS: Details of all cancer patients in the Munich region are recorded by the Munich Cancer Registry. Rectal cancer patients with an invasive primary tumor diagnosed between 1996 and 1998 were included in this analysis (n=936). Observed and relative survival are presented. Observed survival was also investigated with a Cox proportional hazards regression model. RESULTS: Median follow-up time of survivors was 5.7 years. Five-year relative survival for the whole sample was 62.2%. International Union Against Cancer (UICC) stage was the most important prognostic factor in the multivariate analysis. Compared with the 1992-1999 Surveillance Epidemiology and End Results (SEER) data (62.4%), relative survival for each disease stage and the whole sample were very similar. In comparison with other European registries, Munich patients had slightly higher survival rates per stage (for example, 5-year relative survival in UICC III was 58.3% in Munich, 54.6% in South East Netherlands, 33.3% in Modena and 47.4% in Cote d'Or); however, more patients in Munich were in higher disease stages with worse prognoses, indicating poorer early detection. CONCLUSIONS: These results indicate that treatment of rectal cancer in Munich is good, but early detection could be improved. Cancer registries should publish their population-based stage data to ensure quality of care and provide regular feedback to health-care workers and decision makers. Comparisons between countries without stage data should be conducted cautiously.