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Biomedical subjects

H W von Heyden

Publications and source records attributed to H W von Heyden.

At least 19 recordsLinked to original sources
PubMed2001

[Adjuvant chemotherapy in breast cancer--is omission an error?].

Adjuvant chemotherapy in women with breast cancer is currently regarded as standard procedure. An efficacy of 10-20% can only be viewed as modest, even if a statistically significant prolonging of disease-free interval and overall survival has been established. The value of this mode of therapy is questionable because 80-90% of patients are subjected to chemotherapy with no effect, i.e. they would either have remained well regardless, or they are primarily resistant. In both cases, they are prone to suffering significant side effects. The cost-benefit ratio also needs to be taken into consideration. It is therefore recommended that the therapeutic effect is depicted in absolute percentages and not in relative percentages and absolute numbers. Only rendering the results as absolute percentages allows a true comparison between the small number of patients who benefit and the vast majority who do not. Even if this mode of therapy is regularly implemented worldwide by doctors, requested by patients and understandably backed by industry, the central question remains: 'How great do the benefits of a particular therapy have to be, in order to justify its use? Who should set the limits?' For the time being it therefore does not appear to be a mistake not to subject the patients in question to chemotherapy, unless they are part of a study.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

[Clonality and stem cell defects in the molecular pathology of chronic myeloproliferative disorders].

The chronic myeloproliferative disorders (CMD) are characterized by sustained or progressive proliferations of bone marrow cells, affecting one or more lineages in varying combinations. They are classified in 4 subgroups but transitional forms and transformations among the different entities are common. Analysing RFLPs and methylation patterns of X-chromosomal genes we could show, that in each entity granulocytes as well as bone marrow cells are of monoclonal origin. These findings support the view that all forms of CMD have in common that they arise from a multipotent hematopoietic stem cell. CML can be differentiated from all other forms of CMD by the Philadelphia-chromosome which on the molecular level has been revealed as bcr-abl gene junction. We investigated 258 cases of CMD for rearrangement of the bcr gene and found that it selectively occurred in CML. The methods applied can be of diagnostic value in differentiating reactive from neoplastic proliferations by analysis of clonality, and in differentiation of CML from other types of CMD by detection of the bcr-rearrangement.

Bone Marrow↗
PubMed1986

Aminoglutethimide. Penetration of the blood brain barrier.

The uptake of 14C-labeled aminoglutethimide into the brain was investigated in the rat after intracarotid injection according to the method of Oldendorf, as well as in cisternal cerebrospinal fluid obtained by suboccipital puncture after i.v. injection of the drug. The brain uptake index of aminoglutethimide after intracarotid injection was 30.7 + 2.4%. Cerebrospinal fluid/blood quotients after i.v. drug injection were 0.53 at 10 min and 0.26 at 60 min. The results of both methods clearly show that aminoglutethimide easily penetrates the blood brain barrier.

Aminoglutethimide↗
PubMed1986

[Effect of chemotherapy on the survival of patients with far-advanced squamous cell carcinoma of the head and neck. A comparative matched-pair analysis of conventional therapeutic procedures with and without chemotherapy].

Forty-four patients, surgically and/or radiologically treated after primary cytostatic treatment, were compared by matched-pair analysis with a historical control group of patients who had been conventionally treated by surgery and/or radiotherapy only. Both groups were largely identical with respect of tumour localisation and classification, regional metastases, and conventional treatment. The disease-free survival and overall survival times did not differ significantly between both groups. It appears that tumour remission following primary cytostatic therapy does not influence survival times. Primary cytostatic treatment offers advantages over conventional therapy only if it is combined with surgical and radiological procedures in selected patients.

Adult↗
PubMed1985

[Blood-brain barrier and the penetration of cytostatic drugs].

The penetration of 12 commonly used anticancer agents through the blood-brain barrier (BBB) was measured in a rat model using a single-injection tissue-sampling technique. Two of the tested drugs penetrated the barrier, but only to a limited extent. Entry of the drugs into the brain tissue critically depends on molecular weight and lipophilia of the respective test compound. For drugs with a molecular weight of less than 500, BBB simply behaves like an oil/water interphase, whereas drugs with a molecular weight greater than 500 are practically excluded from transport through the BBB even if they show a favourable oil/water partition coefficient. However, permeability of cytostatics was strongly increased if short chain alkylglycerols, up to final concentrations of about 0.3 mol/l were added to the injected solution. Under these conditions the Brain-Uptake-Index (BUI) reached values up to about 50% (cyclophosphamide), depending on lipid solubility and molecular dimension of the respective test compound and the alkyl chain length of the glycerol derivative.

Animals↗
PubMed1985

New assay for the O-alkyl cleavage enzyme with alkyl-lysophospholipids as substrates.

The O-alkyl cleavage enzyme is important for the metabolism of cytotoxic alkyl-lysophospholipids. We have developed a simple new method for the determination of the enzyme activity which is based on the formation of water-soluble phosphate during the enzyme reaction. This is the first assay which avoids the use of radiolabeled substrates.

Animals↗
PubMed1984

[Metastasizing adenocarcinoma from an unknown primary tumor].

Metastatic adenocarcinoma without demonstration of the primary tumour was diagnosed within a period of 42 months in 13 women and 11 men, median age 68.5 years. Analysis of initial symptoms, cardinal findings on first examination and pathological laboratory values pointed predominantly to a primary site in the abdomen. The following conclusions were drawn from this study, with all the disadvantages of retrospective analysis: in a majority of patients (14) the tumour mass could be localized in the upper abdomen. Primary sites include pancreas, biliary tract and gallbladder and possibly colon in the differential diagnosis. There is usually not a good response to chemotherapy. On the other hand, it is important to examine all organs for possible primary site of a carcinoma the metastases of which can be successfully treated by chemotherapy or hormones (mammary, ovarian, testicular, thyroid and prostate carcinoma). Taking into account a median survival time of 28 weeks and the fact that 73% of all technical investigations were normal, diagnostic measures should be as few as possible, restricted predominantly to clinical and biochemical ones, radiography of the thorax, abdominal ultrasound, digital pelvic examination, mammography, and serological and cytological tumour parameters.

Abdominal Neoplasms↗
PubMed1984

[Cytostatic therapy of advanced squamous cell carcinoma of the head and neck. A randomized study comparing cis-dichlorodiammineplatinum(II) and bleomycin with methotrexate and vindesine].

79 patients were randomized and treated either with cis-DDP 33 mg/kg i.v. day 1 and BLM 15 mg/m2 i.v. continuously day 2-6 (arm A) or less aggressively with MTX 30 mg/m2 i.v. day 1 + 6 and VDS 3 mg/m2 day 2 + 7 (arm B). Patients with inadequate response were further treated with the alternative regimen ("cross over"). Regarding response rates therapy A was superior to B (p = 0.01) respectively p = 0.05 for the cross over patients. Not pretreated in comparison to pretreated patients demonstrated not significantly better results. Pretreated patients had statistically superior response rates with arm A than with arm B (p = 0.05). All other prognostic factors were without any influence on treatment results. CR induced by chemotherapy (2 X) in not pretreated patients could be increased by additional surgery and X-ray therapy (CR = 26X). Survival times demonstrated no difference between both regimes. Chemotherapy was of less influence on median survival times after 39 months than in comparison to post-chemotherapeutically performed surgery +/- radiotherapy in 44 not pretreated patients. Chemotherapy: CR + PR to MR + NC + PD 16 respectively 13 months with 38 respectively 48% survivors (p = 0.25). Surgery +/- radiotherapy: CR + PR median not reached yet, MR + NC + PD 13 months with 60 respectively 18% survivors (p = 0.001).

Adult↗
PubMed1984

[Results of drug therapy with cisplatin and 5-fluorouracil in squamous cell carcinoma of the head and neck region].

30 patients with advanced squamous cell carcinoma of the head and neck received initial chemotherapy with Cisplatin (100 mg/m2 i.v. day 1) and 5-Fluorouracil (1000 mg/m2 as 24-hour-infusion day 2-6). 1 patient reached complete remission, 16 patients presented a partial remission, 11 patients showed little response and 2 patients had progressive disease. Following chemotherapy, 29 patients were referred to surgery and/or irradiation. 16 patients received radical surgery. The surgical specimen of 5 patients had no histological evidence of cancer. Objective and subjective side effects of chemotherapy were serious and some patients refused further treatment or were rejected. The results were compared with the data from the literature. The considerably better results from Decker and Weaver et al. were partially explained by an overestimation of remission quality by clinical evaluation and by more therapy courses. At this time, there is no evidence of any benefit from chemotherapy, because there is no data on relapse free survival and over all survival. The position of chemotherapy in the multimodality treatment programme of head and neck cancer still needs to be discussed further.

Adult↗
PubMed1984

[Indications for cytostatic therapy of recurrent cancer].

28 patients with recurrent squamous cell carcinoma of the Head and Neck underwent consecutive chemotherapy. Two different regimens were used: cis-platinum plus bleomycin and methotrexate plus vindesine. The former seemed to produce a better response to the latter, but neither differed in its influence on survival. Those patients in whom further radiation therapy or surgery was possible had the longest survival times. Two out of 28 patients who had surgery are still alive 36 months later. The indications for consecutive chemotherapy for recurrent squamous cell carcinoma ought to take into account the age and general condition of the patient, the extent of the recurrence and the possibility of further therapeutic measures.

Adult↗
PubMed1984

[Results of primary chemotherapy in 44 patients with advanced squamous cell carcinoma in the area of the head and neck].

44 patients with advanced squamous cell carcinoma of the head and neck were randomized and treated preoperatively either with arm "A": cis-DDP (3 mg/kg iv day 1) and BLM (15-20 mg iv continuously day 2-6) or arm "B": MTX (30 mg/m2 iv day 1 + 6) and VDS (3 mg/m2 iv day 2 + 7). Treatment with arm "A" was superior producing 73% complete and partial remissions (CR + PR) compared to 40% for arm "B" (p = 0,05). The number of patients with CR could be increased from 2 to 26 by surgery and/or radiotherapy. The median survival for patients with chemotherapeutically induced CR and PR was 16 months but this did not differ significantly from the median survival (13 months) of non responders (p = 0.25). For patients with CR and PR achieved by surgery and/or x-ray therapy the median survival point has not yet been reached, and this is significant compared to the non responders (p = 0.001). Five of 26 patients with CR died after 39 months of observation and 6 are living with recurrence. In addition to clinical trials, chemotherapy is indicated for patients with inoperable tumours. The value of chemotherapy can only be answered by randomized trials comparing chemotherapy combined with standard procedures against surgery and radiotherapy alone.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Intra-arterial perfusion therapy with 5-fluorouracil in patients with metastatic colorectal carcinoma and intractable pelvic pain.

In a phase-II trial, 18 patients with intractable pelvic and perineal pain caused by local recurrent and/or metastatic colorectal carcinoma resistant to combinations of analgesics, systemic cytostatic chemotherapy and/or radiation were treated with intra-arterial perfusion therapy using 15-30 mg 5-FU/kg body wt./day for 1-5 days. Of 18 patients, ten achieved complete pain relief for 3-32 weeks (mean, 15.7 weeks); after the perfusion therapy eight used less than 50% of the amount of analgesics required before treatment; one patient had only a minor response; two patients were treated unsuccessfully. Side effects were mild and controllable. One patient died subsequent to arterial embolism in the leg where the catheter was placed; pelvic perfusion therefore appears risky in patients with severe arteriosclerosis.

Adult↗