Metabolic panniculitis: alpha‐1 antitrypsin deficiency panniculitis and pancreatic panniculitis

Panniculitis can be the initial presentation of both alpha‐1 antitrypsin deficiency and pancreatic disease. They can both present with abscess‐like draining nodules, but may present like other forms of panniculitis with erythematous nodules. It is important to consider these in the differential diagnosis of patients presenting with panniculitis. Alpha‐1 antitrypsin deficiency is a relatively common disorder mainly affecting the lungs and liver. It frequently goes undiagnosed, yet critical interventions can be made to minimize disease progression. Panniculitis associated with alpha‐1 antitrypsin deficiency can be difficult to treat. Pancreatic panniculitis occurs in less than 3% of patients with underlying pancreatic disease and is often associated with arthritis. Diagnosis and treatment of the underlying pancreatic disease is imperative.     

Cholecystokinin influences pancreatic trophism following total gastrectomy in rats

In rats, total gastrectomy (TG) has been shown to induce pancreatic hyperplasia and increased tissue concentrations of pancreatic trypsin and amylase, whereas lipase concentration was decreased. We performed total gastrectomy with the additional insertion of a duodenal tube in 17 rats. A central venous catheter was placed after 3 wk. The control groups consisted of sham-operated rats with a gastrotomy plus duodenal tube and a group of rats with only a duodenal tube. The rats received meal stimulation with a 6 mL liquid diet (3 mL oil, 2 mL amino acid solution, and 1 mL glucose) via duodenal tube upon recuperation. Blood samples were taken before as well as 5, 15, 30, and 60 minutes after the meal and analyzed for insulin, pancreatic glucagon, gastrin, and CCK by specific RIA techniques. Glucose tolerance was found to be impaired after total gastrectomy. Though insulin release was delayed compared to the controls, the integrated postprandial output was unchanged.     

The immunogenicity of insulin preparation. Antibody levels before and after transfer to highly purified porcine insulin

Summary Ninety-two insulin-dependent diabetics (aged 4–20 years, mean±SD: 13±4) with a duration of diabetes from 2 to 17 years (7±3) were transferred from Lente or NPH (5 × crystallised insulin) to Monotard insulin (highly purified insulin). Total serum immunoreactive insulin levels and concentrations of antibodies against insulin, porcine proinsulin, a-component and pancreatic polypeptide were determined prior to [I] and at a mean of 220 [II], 460 [III], 830 [IV], and 1170 [V] days after the change. All but two subjects had insulin antibodies (IgG) at the start, with a mean value of 2864 U/ml. There was a significant fall in the mean insulin antibody level between [I] and [II] to 2165 U/ml (p<10^-7), followed by an increase between [II] and [III] whereafter a slight decrease was observed being significant between [III] and [IV], as well as between [IV] and [V] (p<0.05); some patients showed a constant fall over the entire period, while others showed fluctuations. Total serum insulin showed a similar pattern, with a mean value of 1141 U/ml at [I] declining to 522 U/ml at [V]. The percentage fall between [I] and [V] was greater (54%) than that in the insulin antibodies (30%). Antibodies against acomponent, proinsulin and pancreatic polypeptide were present in 96%, 72% and 41% of the patients respectively before the change in therapy. There was a decline in these antibodies between each sampling (p values between <10^-3 and 10^-8) and, at the end of the investigation antibodies against a-component were above the detection limit in only 4 patients, and none of the patients showed antibodies against proinsulin or pancreatic polypeptide. Thus, removal of the impurities, including the hormonal contaminants of insulin, leads to a slow fall in antibodies to insulin and a much faster disappearance of antibodies against acomponent, proinsulin and pancreatic polypeptide.     

Detection of K-<Emphasis Type="Italic">ras</Emphasis> mutations in the plasma DNA of pancreatic cancer patients

Background In pancreatic cancers, K-ras mutations have been found frequently (80%–100%), and they could be a good marker to detect tumor DNA in the plasma. Several studies have indicated that polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) analysis of K-ras mutation was a useful method for the detection of hepatic and lymph node metastasis of pancreatic cancer. However, this method sometimes exhibited false-positive results, and the rate of K-ras mutation might thus be overestimated in these tissues. To diagnose pancreatic cancer correctly at an early stage, we attempted to detect tumor DNA in the plasma of pancreatic cancer patients using a more sensitive and specific method.Methods We examined 28 pancreatic cancer patients using a sensitive mutation-specific mismatch ligation assay for K-ras gene mutations in primary tumors and paired plasma samples.Results K-ras gene mutations were detected in 26 of the 28 (93%) pancreatic cancers. We also found the same mutations in 9 of these 26 (35%) patients in their plasma DNA. This mutation was found even in the plasma of patients with TNM stage II cancer.Conclusions Genetic alterations present in the tumors of pancreatic cancer patients can be detected in their plasma, and this approach is potentially applicable for cancer screening and the monitoring of this deadly disease.     

Relation of sweat chloride concentration to severity of lung disease in cystic fibrosis

In cystic fibrosis (CF), sweat chloride concentration has been proposed as an index of CFTR function for testing systemic drugs designed to activate mutant CFTR. This suggestion arises from the assumption that greater residual CFTR function should lead to a lower sweat chloride concentration, as well as protection against severe lung disease. This logic gives rise to the hypothesis that the lower the sweat chloride concentration, the less severe the lung disease. In order to test this hypothesis, we studied 230 patients homozygous for the DeltaF508 allele, and 34 patients with at least one allele associated with pancreatic sufficiency, born since January 1, 1955, who have pulmonary function data and sweat chloride concentrations recorded in our CF center database, and no culture positive for B. cepacia. We calculated a severity index for pulmonary disease, using an approach which takes into account all available pulmonary function data as well as the patient's current age and survival status. Patients with alleles associated with pancreatic sufficiency had significantly better survival (P = 0.0083), lower sweat chloride concentration (81.4 +/- 23.8 vs. 103.2 +/- 14.2 mEq/l, P < 0.0001), slower rate of decline of FEV(1) % predicted (-0.75 +/- 0.34 vs. -2.34 +/- 0.17% predicted per year), and a better severity index than patients homozygous for the DeltaF508 allele (median 73rd percentile vs. median 55th percentile, P = 0.0004). However, the sweat chloride concentration did not correlate with the severity index, either in the population as a whole, or in the population of patients with alleles associated with pancreatic sufficiency, who are thought to have some residual CFTR function. These data suggest that, by itself, sweat chloride concentration does not necessarily predict a milder pulmonary course in patients with cystic fibrosis.     

肝门部胆管癌的MRI及MRCP的诊断价值

目的探讨MRI及MRCP检查对肝门部胆管癌的诊断价值。方法采用0.35 T磁共振成像系统,回顾分析26例肝门部胆管癌的MRI及MRCP表现。结果 MRI显示肝门部肿块26例,增强动脉期大多数轻中度强化,延迟明显强化;肝门部胆管形态改变20例,肝内胆管扩张26例;MRCP显示肝门区胆管的空虚区,左右肝管在汇合前中断、肝内胆管呈中度或重度扩张,呈软藤征。结论肝门部胆管癌在磁共振成像上有特征性的表现,MRI及MRCP是显示胆管癌的最佳影像学方法。     

胰腺癌微环境中胰腺星状细胞(PSC)分泌的细胞因子为药物靶点的研究进展

 胰腺癌是一种发病率高、病死率高的恶性疾病,进展快、恶性程度高、预后差,其生存率一直得不到提高。肿瘤进展不仅取决于肿瘤细胞本身的生物学特性,而且与多种非肿瘤性基质细胞构成的微环境密切相关。胰腺星状细胞是产生癌周基质及其相关因子的重要细胞,近年来成为胰腺癌研究新热点。本文论述了胰腺星状细胞分泌的多种能够促使胰腺癌增殖迁移的细胞因子(TGF β,IL 6,FGF2和TGF α)及其已经发现的靶向药物,这些细胞因子有望成为药物筛选靶点。