Search PubMed⌕ Search

Biomedical subjects

K Schulmann

Publications and source records attributed to K Schulmann.

11 recordsLinked to original sources

The p53 codon 72 variation is associated with the age of onset of hereditary non-polyposis colorectal cancer (HNPCC).

The polymorphic variants at codon 72 of the p53 gene were shown to be functionally distinct in vitro, whereby the arginine (arg) variant induces apoptosis more efficiently than the proline (pro) variant. From the evidence that the DNA mismatch repair system and p53 interact to maintain genomic integrity, we hypothesized that the codon 72 variation may influence the age of onset of disease in HNPCC patients. We tested 538 patients for p53 codon 72 variants, including 167 unrelated patients with pathogenic germline mutations in MSH2 or MLH1 and colorectal carcinoma as first tumour, 126 patients with sporadic microsatellite stable colorectal cancers, and 245 healthy controls. The median age of onset was 41, 36, and 32 years for MSH2 or MLH1 mutation carriers with arg/arg, arg/pro, and pro/pro genotypes, respectively. The log rank test revealed significant differences in the age of onset between arg/arg and pro/pro individuals (p = 0.0002) and in arg/pro versus arg/arg and pro/pro individuals (p = 0.0026 and p = 0.0217, respectively). A Cox regression model indicated an additive mode of inheritance. No significant differences in age of onset were observed among different genotype carriers with microsatellite stable tumours. Our results suggest that p53 codon 72 genotypes are associated with the age of onset of colorectal carcinoma in a mismatch repair deficient background in a dose dependent manner. These findings may be relevant for preventive strategies in HNPCC.

Adaptor Proteins, Signal Transducing↗

[Diagnostic utility of capsule endoscopy in occult gastrointestinal bleeding].

BACKGROUND AND OBJECTIVE: The video-capsule endoscopy (CE) of the small intestine is a novel innovative procedure for outpatient use that can detect even small lesions of the mucosa of the small intestine. Aim of this retrospective clinical study was to evaluate the diagnostic value of CE in a clinical routine setting. PATIENTS AND METHODS: Between July 2001 and October 2002 we investigated 42 patients with suspected gastrointestinal bleeding by CE. In all patients, the previous upper and lower endoscopy work-up was normal. In some cases additional procedures such as bloodpool scintigraphy, angiography, small-bowel enteroclysis or push-enteroscopy were performed. RESULTS: CE detected relevant pathological findings in 23 out of 42 Patients (55 %). The majority of findings in the CE consisted of angiodysplasia (n = 16), ulcer and haemorrhagical erosions (n = 10), one Ulcus Dieulafoy and additional polyps of the small intestine (n = 2). In 4 cases an inflammatory small-bowel disease was detected. These findings could be confirmed by Re-endoscopy. The information provided was helpful to direct further diagnostic and treatment options. In 14 cases (33 %) CE-findings steered additional diagnostic and therapeutic steps. We conclude that CE is safe and has a high diagnostic yield. CONCLUSION: M2A video CE is likely to become an integral part of the algorithm of diagnostic of occult gastrointestinal bleeding after exclusion of other causes of anemia and negative upper and lower endoscopy work-up.

Adult↗

Endoscopically assisted video capsule endoscopy of the small bowel in patients with functional gastric outlet obstruction.

Since the introduction in 2001 of M2A video capsule imaging of the small bowel in humans, this technique has been used increasingly in patients with disorders of the small bowel. In particular the assessment of small obscure gastrointestinal bleeding sources and the detection of shallow inflammatory lesions in the small bowel, have been greatly facilitated by this novel imaging procedure. We report two cases of patients with obscure gastrointestinal bleeding, in whom normal passage of the capsule through the antroduodenal junction was inhibited. This was because of delayed gastric emptying in both patients, which was presumably caused by functional impairment of pyloric motility. To facilitate capsule transport into the small bowel, after swallowing the capsule each patient underwent unsedated upper gastrointestinal endoscopy during which the capsule was grasped with a polypectomy snare, directly transported through the pylorus, and finally released upon arrival in the second portion of the duodenum. Capsule recordings revealed the source of bleeding in both patients and their medical or surgical treatment was subsequently escalated. Capsule imaging of the small bowel facilitated by esophagogastroduodenoscopy (EGD) is safe, and can be applied when patients have functional disorders of pyloric motility.

Endoscopy, Gastrointestinal↗

Enrichment of mutant KRAS alleles in pancreatic juice by subtractive iterative polymerase chain reaction.

SUMMARY: The detection of mutant tumor genes holds great promise for an early diagnosis of primary tumors and residual malignant disease. When few tumor cells are present with an excess of nonmalignant cells of the same lineage, the excess of wild-type alleles over mutant tumor alleles presents an analytical problem. The subtractive iterative PCR (siPCR) assay presents a new approach to solving this problem. To achieve an enrichment of mutant alleles, wild-type alleles are removed by differential hybridization to complementary oligonucleotides spanning the region of the gene in which point mutations are expected. The nonbound fraction is reamplified by PCR. By iterating this process, mutant alleles can be detected in the presence of an excess of wild-type alleles with high sensitivity. To prove the feasibility of siPCR, pancreatic juice samples were analyzed for KRAS mutations. Pancreatic juice obtained from patients with pancreatic carcinoma or chronic pancreatitis during endoscopic retrograde cholangiopancreatography was analyzed for point mutations in codons 12 and 13 of the KRAS gene. In each of six samples from tumor patients, mutations in codon 12 were detected. One of nine samples from patients with chronic pancreatitis scored positive.

Alleles↗

Tumour regression in non-small-cell lung cancer following neoadjuvant therapy. Histological assessment.

In the scope of a prospective multi-centre study after neoadjuvant combined chemotherapy (carboplatin, ifosfamide, etoposide, vindesine) and radiotherapy (45 Gy) 40 resection specimens of locally advanced non-small-cell lung cancer were analysed in order to establish reproducible pathological/anatomical results of tumour regression. Resection specimens of 28 squamous cell carcinomas and 12 adenocarcinomas were investigated using serial sections of the primary lesion. The mean age of the patients was 57 years. The results were compared to spontaneous regressive changes in a control group of 50 untreated non-small-cell lung cancers. Marked scarry fibrosis in the region of the former primary tumour, concentric foci of fresh tumour necroses and surrounding foam cell clusters with transition into vascular granulation tissue could be established as characteristic features of therapy-induced tumour regression, whereas untreated carcinomas revealed necroses with adjoining vital tumour tissue. Using a three-step regression system, 3 tumours could be classified as grade I (no or only slight tumour regression), 10 tumours as grade IIA (marked but incomplete tumour regression, more than 10% vital tumour tissue), 20 tumours as grade IIB (less than 10% vital tumour tissue) and 7 tumours as grade III (complete tumour regression without vital tumour tissue). After a median follow-up period of 32.3 months in patients with grade IIB or III tumour regression ("responders") the median survival time of 27.9 months was found to be significantly longer than in patients with grade I or IIA tumour regression ("non-responders") with a median survival period of 13.7 months (log-rank test, P = 0.020). The resection specimens analysed, which were obtained 7 weeks (on average) after the end of radiochemotherapy, did not show specific changes due to preoperative therapy, but quite characteristic histological alterations in the former tumour area were registered, which had been induced by combined neoadjuvant radiation and chemotherapy. The grade of therapy-induced tumour regression could be shown to be a significant prognostic factor in non-small-cell lung cancer.

Adenocarcinoma↗

[Regression grading of neoadjuvant non-small-cell lung carcinoma treatment].

In the scope of a multi-center-study 35 resection specimens from patients with locally advanced non-small cell lung cancer after neoadjuvant chemotherapy and radiation were processed histologically and graded according to the following regression grading system: grade I: no or only slight, in general spontaneous tumor regression, grade IIa: incomplete tumor regression with more than 10% and grade IIb less than 10% vital tumor tissue as well as grade III: complete tumor regression. In 15 patients with grade II a to III tumor regression roughly concentric foci of various size with a sequence of central tumor necrosis, narrow foam cell rim, vascular granulation tissue and peripheral scar formation were demonstrated as characteristic feature of response to neoadjuvant therapy. In patients with grade IIb to III tumor regression ("responders") median survival time of 27.9 months was significantly longer than in patients with grade I to II a tumor regression ("non-responders") with a median survival time of 12.7 months.

Adult↗

[Intrauterine devices for contraception? Results of an inquiry conducted in the BRD in 1976].

The results of the 1098 responses to a questionnaire show a remarkable increase in the use of intra-uterine devices (IUD) as a method of contraception (especially in the last 3 years) in the FRG too. The main reasons for the insertion of IUD were specified as "incompatibility" with the pill or "weariness induced through constant use of the pill". IUD are also used by nulliparae. At the moment T-shaped models containing copper are most popular. The majority of insertions are performed without general anaesthesia. The optimal length of time for wearing an IUD is considered to be 2 years or more. The foremost reasons for removal of IUD are bleeding or pain. Failures (pregnancies) however, are rather frequently recorded. Most gynecologists remove the IUD if pregnancy has occurred and in this case only few of them try to maintain the pregnancy on the patients request. In 1976, the majority of gynecologists attended patients composed of 40 : 1 users of the pill : users of IUD. Numerically speaking therefore, IUD are the method which actually takes second place. In our opinion however, if attention is paid to indications and contra-indications and to the necessity for intensive education of the patient, IUD are a real alternative to the pill and to the increasing use of any type of female sterilization.

Contraception↗