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Biomedical subjects

P Richter

Publications and source records attributed to P Richter.

At least 19 recordsLinked to original sources

Treatment of bendamustine and prednisone in patients with newly diagnosed multiple myeloma results in superior complete response rate, prolonged time to treatment failure and improved quality of life compared to treatment with melphalan and prednisone--a randomized phase III study of the East German Study Group of Hematology and Oncology (OSHO).

PURPOSE: This randomized phase III study compared bendamustine and prednisone (BP) to standard melphalan and prednisone (MP) treatment in previously untreated patients with multiple Myeloma (MM). PATIENTS AND METHODS: To be included, patients had to have histologically and cytologically proven stage II with progressive diseases or stage III MM. They were randomly assigned to receive BP (n=68) or MP (n=63). The primary endpoint was the time to treatment failure (TTF). Secondary endpoints included survival, remission rate, toxicity and quality of life. RESULTS: The overall response rate was 75% in the BP and 70% in the MP group. A significantly higher number of patients treated with BP achieved a complete remission than did patients receiving MP (32 vs. 13%; P=0.007), and the maximum response was achieved more rapidly in patients treated with BP compared to those receiving MP (6.8 vs. 8.7 cycles; P<0.02). TTF and remission duration were significantly longer in the BP group. Patients receiving BP had higher QoL scores and reported pain less frequently than patients receiving MP. CONCLUSION: BP is superior to MP with respect to complete remission rate, TTF, cycles needed to achieve maximum remission and quality of life and should be considered the new standard in first-line treatment of MM patients not eligible for transplantation.

Adult↗

Germline MSH2 and MLH1 mutational spectrum including large rearrangements in HNPCC families from Poland (update study).

Germline mutations in the DNA mismatch repair genes MSH2 and MLH1 account for a significant proportion of hereditary non-polyposis colorectal cancer (HNPCC) families. One approach by which development of an efficient DNA-testing procedure can be implemented is to describe the nature and frequency of common mutations in particular ethnic groups. Two hundred and twenty-six patients from families matching the Amsterdam II diagnostic criteria or suspected HNPCC criteria were screened for MSH2 and MLH1 germline mutations. Fifty different pathogenic mutations were found, 25 in MSH2 and 25 in MLH1. Twenty-four of these had not previously been described in other populations. Among our 78 families with MSH2 or MLH1 mutations, 54 (69.2%) were affected by recurrent mutations including 38 found at least twice in our own series. Two of the most frequent alterations were a substitution of A to T at the splice donor site of intron 5 of MSH2 and a missense change (A681T) of MLH1 found in 10 and eight families, respectively. Among large deletions detected by the multiplex ligation-dependent probe amplification assay, exon 9 deletions in the MSH2 gene were found in two families. Our results indicate that a screening protocol specific for the Polish population that is limited to the detection of all reported mutations will result in the identification of the majority of changes present in MLH1 and MSH2 genes in Polish HNPCC kindreds.

Adaptor Proteins, Signal Transducing↗

The incidence of sleep apnea in patients with stroke or transient ischemic attack.

Disorders of breathing during sleep are defined as cessation or reduction of air flow thorough the upper airway, accompanied by a decrease of oxygen saturation. The results of many studies underline the association between sleep-disordered breathing (SDB) and cerebrovascular disorders. SDB, mostly obstructive sleep apnea syndrome (OSAS), is believed to be an independent risk factor of stroke and is related to poor outcome and increased long-term stroke mortality. The present study evaluated the frequency of SDB in patients with stroke or transient ischemic attack transient ischemic attack. We studied 43 patients (mean age 68.5 +/-11.0), which included 35 males and 8 females, with acute stroke (n=37) and transient ischemic attack (n=6). The assessment included body mass index (BMI), age, cardiovascular risk factors, and localization of stroke. All patients underwent all-night screening for SDB with a portable 8-channel recorder. The apnea/hypopnea index (AHI) for the whole group was 13.3 +/-15.2. AHI <5 was found in 16 patients. Overall, SDB was present in 27 (62.8%) patients with stroke and transient ischemic attack, stratified into those with AHI 5-10, (10 patients), 10-20 (8 patients), and AHI>20 (9 patients). In 15 patients, there was an increase in AHI >or=5 on assuming the supine position. The patients' mean BMI was 27.8 +/-4.7. The analysis of BMI, age, and localization of stroke was not sufficient to identify patients with high risk for SDB. We submit that overnight screening for SDB should be routinely performed in every patient after stroke and transient ischemic attack and it should become a diagnostic tool in neurological departments.

Aged↗

Bendamustine, vincristine and prednisone (BOP) versus cyclophosphamide, vincristine and prednisone (COP) in advanced indolent non-Hodgkin's lymphoma and mantle cell lymphoma: results of a randomised phase III trial (OSHO# 19).

PURPOSE: The purpose of this study was to compare the efficacy and toxicity of bendamustine, vincristine + prednisone (BOP) with a standard regimen of cyclophosphamide, vincristine + prednisone (COP) in patients with previously untreated advanced indolent non-Hodgkin's lymphoma (NHL) and mantle cell lymphoma. METHODS: A total of 164 patients with follicular lymphoma (grade 1/2), mantle cell lymphoma or lymphoplasmacytic lymphoma (immunocytoma) was randomised to treatment with vincristine 2 mg (day 1) and prednisone 100 mg/m2 (days 1-5) + bendamustine 60 mg/m2 (days 1-5) or + cyclophosphamide 400 mg/m2 (days 1-5) for a total of eight 21-day cycles. RESULTS: The rate of complete remission was 22% with BOP and 20% with COP. The projected 5-year survival rate was 61% with BOP and 46% with COP. The BOP-associated 5-year survival advantage almost reached significance in the subgroup of patients who responded to therapy (74% vs. 56%; P = 0.05), and did reach significance in responders who did not receive interferon maintenance therapy (70% vs. 47%; P = 0.03). Toxicity was acceptable in both treatment groups, although alopecia and leucopenia were more severe with COP. CONCLUSIONS: Bendamustine can efficaciously and safely replace cyclophosphamide, as used in standard COP therapy, for the treatment of patients with indolent NHL and mantle cell lymphoma. Long-term survival data suggest a clinically significant benefit for patients treated with BOP.

Adult↗

[Rare cause of long QT and resuscitation-requiring torsade de pointes tachycardia].

A 62 year old patient underwent an intraoperative pancreas biopsy because of a pancreas head process. On 13(th) and 20(th) postoperative day a short syncope episode occurred. On that days calcium blood levels were 1,82 and 1,74 mmol/l, respectively. On 13(th) postoperative day QT(c) interval was 565 ms. On 26(th) postoperative day the patient was resuscitated because of torsade de pointes tachycardia. His actual calcium blood level was 1,47 mmol/l and QT(c) interval 627 ms. An extensive diagnostic work-up revealed no evidence of cardiac disease. After calcium substitution QT interval normalised. During a follow-up period of 16 months the patient remained without symptoms.

Calcium↗

[Simultaneous analysis of t(X;18) by FISH- und SYT/SSX-RT-PCR in synovial sarcoma].

Synovial sarcoma diagnosis and differential diagnostic distinction from other spindle cell sarcomas may be difficult. In these cases the detection of the t(X;18) translocation by FISH and RT-PCR is diagnostically extremely helpful. This study was aimed at the question whether or not simultaneous use of both methods is required for evidence of t(X;18) translocation.Paraffin-embedded tumour specimens from 53 patients were included in the study which were considered to be possible synovial sarcomas on the basis of histological aspect and immunohistochemical profile. Detection of t(X;18) was performed using FISH and RT-PCR simultaneously. Nuclei and amplifiable RNA could be isolated from 39 of the 53 included cases (75%). In 72% of these 39 cases FISH and RT-PCR showed identical negative or positive results. The remainder of the cases (28%) showed either a typical PCR product or a positive FISH signal.In conclusions FISH could be confirmed by typical PCR products and is therefore qualified as an internal quality control. Nevertheless tumour biological and methodical reasons have an important influence on both methods. Consequently in difficult cases simultaneous FISH and RT-PCR analysis is necessary for a clear evidence of t(X;18) translocation.

Chromosomes, Human, Pair 18↗

Bifocal esophageal and rectal cancer palliatively treated with argon plasma coagulation.

Primary multiple neoplasms make a serious diagnostic and therapeutic problem. They occur infrequently; however, they must be considered in the diagnosis as the detection of simultaneous neoplastic foci requires change of therapeutic approach. We present a case of a patient with synchronous esophageal and rectal cancer treated at the Department of Surgery. Because of the advanced neoplastic process and concomitant diseases, the patient was qualified for minimally invasive procedures with recanalization using argon plasma coagulation to avoid injuring palliative procedures and to improve quality of life. The patient died of the primary disease without symptoms of gastrointestinal tract obstruction.

Adenocarcinoma↗

Determination of tar, nicotine, and carbon monoxide yields in the mainstream smoke of selected international cigarettes.

OBJECTIVE: Survey of nicotine, tar, and carbon monoxide (CO) smoke deliveries from 77 cigarette brands purchased in 35 countries was conducted using a standardised machine smoking method. The goal of this study was to determine regional variations and differences in the tar, nicotine, and CO smoke yields of a cigarette brand manufactured by a leading transnational corporation and of non-US locally popular cigarette brands. DESIGN: The majority of the cigarettes were purchased in each of the participating countries by delegate members of the World Health Organization and forwarded to the Centers for Disease Control and Prevention for analysis. Smoke deliveries were determined using a standardised smoking machine method and subsequent gravimetric and gas chromatography analysis. RESULTS: The smoke deliveries varied widely. Mainstream smoke deliveries varied from 6.8 to 21.6 mg tar/cigarette, 0.5 to 1.6 mg nicotine/cigarette, and 5.9 to 17.4 mg CO/cigarette. In addition to the smoke deliveries, the cigarettes were examined to determine physical parameters such as filter composition, length, and ventilation levels. CONCLUSION: Analysis of the smoke deliveries suggested that cigarettes from the Eastern Mediterranean, Southeast Asia, and Western Pacific WHO regions tended to have higher tar, nicotine, and CO smoke deliveries than did brands from the European, American, or African WHO regions surveyed.

Air Pollutants↗

Gravitaxis and graviperception in flagellates.

There is strong evidence that gravitactic orientation in flagellates and ciliates is mediated by an active physiological gravireceptor rather than by passive alignment of the cells in the water column. In flagellates the threshold for graviorientation was found to be at 0.12 x g on a slow rotating centrifuge during the IML-2 mission on the Shuttle Columbia and a subsequent parabolic rocket flight (TEXUS). During the IML-2 mission no adaptation to microgravity was observed over the duration of the space flight, while gravitaxis was lost in a terrestrial closed environmental system over the period of almost two years. Sedimenting statoliths are not likely to be involved in graviperception because of the small size of the cells and their rotation around the longitudinal axis during forward locomotion. Instead the whole cytoplasmic content of the cell, being heavier than the surrounding aqueous medium (1.05 g/ml), exerts a pressure on the lower membrane. This force activates stretch-sensitive calcium specific ion channels which can be inhibited by the addition of gadolinium which therefore abolishes gravitaxis. The channels seem to mainly allow calcium ions to pass since gravitaxis is blocked by the addition of the calcium ionophore A23187 and by vanadate which blocks the Ca-ATPase in the cytoplasmic membrane. Recently, a gene for a mechanosensitive channel, originally sequenced for Saccharomyces, was identified in Euglena by PCR. The increase in intracellular free calcium during reorientation can be visualized by the fluorophore Calcium Crimson using laser excitation and image intensification. This result was confirmed during recent parabolic flights. The gated calcium changes the membrane potential across the membrane which may be the trigger for the reorientation of the flagellum. cAMP plays a role as a secondary messenger. Photosynthetic flagellates are suitable candidates for life support systems since they absorb CO2 and produce oxygen. Preliminary experiments are discussed.

Acceleration↗

Proliferative activity in primary ovarian carcinoid tumors.

The proliferative potential of six primary ovarian carcinoids with different clinical outcome and histogenetic origin was examined immunohistochemically. The results showed that two cases with extremely high level of proliferative activity were associated with metastatic spread. In the remaining tumors, the examined factor was found to be at low level comparable with excellent prognosis of typical carcinoids in other locations. The preliminary results showed a possibility of a prognosis prediction according to typing of the ovarian carcinoids into two categories, i.e., tumors of low and intermediate malignancy. Topoisomerase II-alpha and Ki-67 are suitable markers giving valuable information about this phenomenon.

Aged↗

[Victims of Nazi euthanasia, the so-called T4 action. First results of a project at the German Federal Archives to disclose records of killed patients].

In 1990, previously unknown documents dated from the Nazi era were found in Berlin. They had been preserved in the central archives of the Ministry for State Security (MfS), the secret service of the now former German Democratic Republic (GDR). Nearly 30,000 psychiatric patient files turned out to comprise the smaller part of the records of patients who had been murdered in the 1940/41 "T4 action". More than 70,000 patients of psychiatric asylums were killed by gas in this first campaign of extermination during Nazism, and their files were believed to have been lost. Based on a project to be funded by the German Research Association, this paper offers a brief survey of the developments in historical research about Nazi "euthanasia" and the theories interpreting historical information. The paper will also present a research project dedicated to the memory of the victims of the "T4 action" and to the rediscovered files now conserved in the German Federal Archives in Berlin. The aim is to offer a systematic analysis of 3,000 records in an effort to contribute to the perception of the victims as individuals. The analysis will also include an examination of the selection criteria stipulated by the Nazi psychiatrists (hereditary illness, incurability, and incapacity to work productively) to select patients for extermination. In this way, the decision-making process, criteria, and motives that led to the killing should become more clear. This empirical analysis will help to answer questions concerning the proportion of eugenic and economic motivations and the Nazi rationale behind the extermination campaigns. The project will build upon an earlier preliminary study of a nonrepresentative sample of 185 files. As a preliminary result, it can be said that most of the victims had been hospitalised over long terms and classified as schizophrenic or feeble-minded. A third of the patients killed were considered invalid and not working, and almost 50% were described as working "mechanically". Five per cent of the victims were working "productively".

Crime Victims↗

[The role of infection and inflammation in the pathogenesis of atherosclerosis].

Pathogenesis of the atherosclerotic process is deemed as multifactorial. To the most important risk factors, besides certain family predisposition, there belongs hypercholesterolemia, arterial hypertension, obesity, diabetes mellitus, smoking and others. In the last years there are more and more data about the role of inflammation and infection in the whole development of atherosclerosis. The witness for this hypothesis is the findings of high parameters of inflammation in involved vessels as well as in the blood of atherosclerosis suffering persons. Opinions about the inflammation theory appear from the 90th. Local sterile inflammation in the subendotelium of the middle and big arteries has been proved to consist of specific immune reaction (activation of the T-lymphocytes) as well as nonspecific characteristic by elevated monocytes in the artery wall during the whole process of atherogenesis. Inflammation in the plaque can trigger and hold several factors engaged in the atherosclerotic process, such as oxidized LDL cholesterol, elevated production of various superoxides, activated macrophages, activated T-lymphocytes, cytokines (IL-1, IL-6, interferon gamma) and lipoprotein Lp (a). In this inflammation process levels of CRP (acute phase protein), fibrinogen and erythrocyte sedimentation are elevated as a reaction of the organism to nonspecific chronic infections. Because of this it is thought that elevated fibrinogen and erythrocyte sedimentation are markers of the cardiovascular risk. Some papers deal with antiinflammatory effects of statins, because these lower CRP levels so they also lower atherosclerotic risk through not only lowering of cholesterol levels. Also asprine, as an antiinflammation agent, changing the CRP levels, would be of benefit for patients with vascular disease because its antiaggregation and antiinflammatory effects. ACE inhibitors are also antiinflamatory through blocking of tissue production of angiotensin II (artery wall and atherosclerotic plaque). Enzymatic inhibitors changing angiotensin can also have a partial antiinflammatory effect. The infection theory is supported also by tracing of some microorganisms in the atherosclerotic plaque or in the blood, as e.g. Helicobacter pylori or Chlamydia pneumoniae; to the autoimmune origin is indicated the presence of the specific immunity reaction against heat shock proteins (HSP) or oxidized LDL. This infection theory offers new therapy possibilities. Therefore eradication for example by antibiotics can lead to stabilization of the atherosclerotic plaque with positive consequences, as it was discovered by many studies.

Animals↗

Anorectal sphincter function and rectal barostat study in patients following transanal endoscopic microsurgery.

BACKGROUND AND AIMS: This study evaluated the effect of transanal endoscopic microsurgery (TEM) on anorectal sphincter functions and determined the risk factors for anorectal dysfunctions (including incontinence). PATIENTS AND METHODS: A study group of 33 patients with small, mobile rectal tumors (adenoma and carcinoma) located up to 12 cm from the anal verge underwent anorectal motility studies (using pull-through anorectal manometry and rectal barostat) and endoanal ultrasound prior to surgery and 3 weeks and 6 months after TEM; controls were 20 healthy volunteers. RESULTS: Resting and squeeze anal pressures were reduced 3 weeks after TEM. Resting anal pressure remained reduced 6 months after surgery; the changes were related to low preoperative levels and to the internal anal sphincter defects rather than to the procedure duration or the type of surgery. High-pressure zone length and vector volume were decreased 3 weeks after TEM and restored 6 months later. Rectoanal inhibitory reflex, reflex sphincter contraction, rectoanal pressure gradients, threshold and maximal tolerable volume of rectal sensitivity, and compliance were significantly changed 3 weeks after TEM; only rectal wall compliance remained low at 6 months. The rectoanal inhibitory reflex, reflex sphincter contraction, rectal sensitivity, and compliance were related to the extent and type of excision (partial or full thickness). Anal ultrasound revealed internal anal sphincter defects in 29% of patients studied 3 weeks after TEM. Only 76% of patients were fully continent. Disturbed anorectal function (including partial fecal incontinence) was observed in up to 50% of patients at 3 weeks. Partial and moderate anorectal dysfunction was found in 21% patients 6 months after surgery. The main risk factors of anorectal dysfunctions following TEM included: postoperative internal anal sphincter defects, low preoperative resting anal pressure, disturbed rectoanal coordination, extent (>50% of wall circumference) and the depth (full thickness) of tumor excision. CONCLUSION: TEM has a relevant but temporary effect on anorectal motility. As a result of TEM procedures 21% of the patients had disturbed anorectal functions, mostly due to the extent or depth of tumor excision (influencing rectal compliance and rectoanal coordination), and to the sphincter defects lowering resting anal pressure. Preoperative anorectal motility studies and anal ultrasound allow the identification of patients with the risk of postoperative anorectal dysfunctions.

Adenocarcinoma↗

Chemotherapy for mobilisation of Ph-negative progenitor cells from patients with CML: impact of different mobilisation regimens.

Mobilised peripheral blood stem cells are widely used for autografting in patients with chronic myeloid leukaemia (CML) and it is generally thought that a high proportion of Ph-negative progenitor cells in the graft is desirable. We report here the results of 91 stem cell mobilisations performed with various chemotherapy regimens followed by G-CSF. We show that mobilisation of Ph-negative cells is possible after diagnosis as well as in advanced stages of the disease. The yield of Ph-negative cells is highly dependent on the chemotherapy regimen: while the combination of idarubicin and cytarabin for 3-5 days (IC3-5) mobilised Ph-negative cells in most patients, high-dose cyclophosphamide was ineffective. Mobilisation of Ph-negative progenitor cells after IC3 was at least as effective as after IC5; however, less apheresis sessions were required, and toxicity was much reduced after IC3. Compared to historical controls, IC was equally effective as the widely used ICE/miniICE (idarubicin, cytarabin, etoposide) protocol. No correlation was found between graft quality and the cytogenetic response to subsequent treatment with interferon-alpha. We conclude that IC3 is an effective and well-tolerated regimen for mobilising Ph-negative cells that compares well with more aggressive approaches such as IC5 and ICE/miniICE.

Adolescent↗

Radiofrequency energy modification of the atrioventricular junction in patients with atrial fibrillation: modes of ventricular response under autonomic blockade and long-term effect.

The short- and long-term effect of radiofrequency (RF) modification of the AV junction on ventricular rate and left ventricular function and the different types of ventricular response during energy application under autonomic nervous blockade were assessed in 28 patients with medically refractory atrial fibrillation. During the successful RF application, ventricular rate slowed progressively (type I response, ten patients) or accelerated at first and then slowed (type II response, 11 patients). Type II response was associated with a more anterior ablation site compared to Type I response. A primary successful outcome was achieved in 21 patients. Inadvertent complete AV block developed in three patients, while in four patients AV nodal ablation was performed after an unsuccessful modification attempt. During 6-month follow-up, the ventricular rate was adequately controlled in only four patients. Among the 16 patients with a recurrence of uncontrolled AF were all 10 patients with type I response and 6 of 11 patients with type II response. One patient died suddenly 10 weeks after the procedure.

Aged↗