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Biomedical subjects

H Müller

Publications and source records attributed to H Müller.

At least 595 records · Page 33Linked to original sources

Short-term and long-term monitoring of the serum level of TPA after radical resection of gastrointestinal or lung cancer.

Radically operated tumour patients (gastrointestinal cancer, n = 10; lung cancer, n = 10) were subjected to continuous prospective monitoring of the serum level of tissue polypeptide antigen (TPA) prior to surgical treatment as well as during the subsequent year. The following observations were made: Immediately after radical surgery the serum level of TPA fell temporarily. During the first 2 weeks following this initial decrease, the serum level of TPA rose. In view of the radical surgical treatment the patients had undergone, this finding is interpreted as being not caused directly by the tumour but by tissue repair or proliferation. It is concluded that the first postoperative control of the serum concentration of TPA should be performed not earlier than 4 weeks after tumour resection. If the level of TPA increased after these 4 weeks, the suspicion of a tumour relapse or metastasization was raised. In single cases, a transient rise of serum TPA may not be due directly to the tumour but to other events, e.g. intercurrent infection. In general, the course of the serum level of TPA did not exhibit a marked difference between patients with gastrointestinal and lung cancer.

Adult↗

Variation and adaptation of Pseudomonas aeruginosa toxicity to HeLa cells and fibroblasts.

The toxic components of supernatants from Pseudomonas aeruginosa cultures directed against HeLa cells and Staphylococcus aureus were evaluated with the aim of discovering interactions. Supernatants of eight different strains of P. aeruginosa were assayed for cytotoxic activity. All were active against HeLa cells; seven were toxic for S. aureus. On repeated suspension of P. aeruginosa in 0.9% sodium chloride solution, a shift from HeLa cell toxicity to staphylococcal lytic activity occurred along with a change of toxic activity from a high (50,000 +/- 5,000) to a low (8,000 +/- 400) molecular weight (MW) range on gel filtration. Addition of protein to the minimal medium of cultures producing material toxic only for S. aureus reactivated the generation of HeLa cell-toxic material. Cultivation of P. aeruginosa in the presence of HeLa cells and a chloramphenicol supplement produced suppression of the generation of material toxic for S. aureus but facilitated that of HeLa-toxic material of high MW. Adaptation of toxicity against fibroblasts developed only on cocultivation of P. aeruginosa together with S. aureus and in the presence of fibroblasts. Under these conditions a strong lytic activity for S. aureus appeared, even in the presence of chloramphenicol. Chloramphenicol caused the material toxic for fibroblasts to elute at a low MW well separated from that toxic for HeLa cells. In contrast to the high-MW toxic substances, the low-MW material did not induce antibodies after injection into rabbits. This may explain failures of vaccination against P. aeruginosa infection and of serum therapy of homologous sepsis in humans.

Bacterial Toxins↗

High incidence of laryngeal carcinoma in a Swiss family.

The article describes a family in which a father and both sons were treated for carcinoma of the larynx. Reports of 21 similar families were collected from the literature. Certain factors occurring in familial cases are discussed (alteration of the sex ratio, early onset of the disease, same histological type and same localization of the cancer in relatives), which could indicate a genetic susceptibility in these families.

Female↗

Assay for thyroid growth stimulating immunoglobulins: stimulation of [3H]thymidine incorporation into isolated thyroid follicles by TSH, EGF, and immunoglobulins from goitrous patients in an iodine-deficient region.

Estimations were carried out of [3H]thymidine incorporation during culture of isolated porcine thyroid follicles in the presence of standard TSH or epidermal growth factor (EGF) both alone and together with anti-TSH or anti-EGF serum, and of immunoglobulins fractionated from the sera of patients from our endemic goitre area with iodine deficiency. A significant stimulation of thymidine incorporation was exerted by TSH when thyroglobulin was present in the culture medium, and also by EGF. TSH stimulation was abolished by anti-TSH serum, in contrast to the effect of EGF. Anti-EGF serum, on the other hand, blocked the effect of EGF, but not that of TSH. The sera of 20 out of 72 patients (27%) with euthyroid goitre (not operated on) and of ten out of 26 patients (38%) with recurrent euthyroid goitre contained immunoglobulins stimulating thyroid growth (TGI). There was no correlation of TGI with other thyroid antibodies. TGI have to be regarded as a pathogenetic factor of euthyroid goitre also in patients from an endemic region especially in recurrent cases.

Animals↗

Purification of Escherichia coli DNA helicase I from plasmid-transformed cells.

DNA helicase I was purified in large quantity from Escherichia coli cells harboring a plasmid that carries the gene encoding helicase I--the traI gene of the F sex factor--cloned in a high copy number vector. Electron microscopic studies on the purified material reveal new properties of the enzyme protein.

DNA Helicases↗

[Isolated modification of the vascular system by vasopressor agents (akrinor, etilefrin, ephedrine, norfenefrine, amezinium) during extracorporeal circulation in man].

The influence of different vasopressors (Akrinor, etilefrine, ephedrine, norfenefrine, ameziniummetilsulfate) on arterial perfusion pressure and oxygenator volume during extracorporeal circulation was compared to a control group. All substances led to an increase in perfusion pressure, thus demonstrating a direct influence on arterial vessels. The rise in arterial pressure after injection of ameziniummetilsulfate persisted during the investigation period, whereas norfenefrine led to a short-lasting, but massive increase. No rise in venous tone was noticed during the investigation period.

2-Hydroxyphenethylamine↗

[Spasticity treatment with spinal morphine or midazolam. In vitro experiments, animal studies and clinical studies on compatibility and effectiveness].

Recent pharmacological investigations have support the hypothesis that spinal modulation of nociception as well as motor coordination is related to the activity of spinal interneurons and that certain spinal transmitters are involved in the control of both regulatory systems. Opioids and benzodiazepines, i.e. endorphin- or GABA-induced mechanisms, may be of importance for spinal treatment of spasticity in the near future. In order to clinically evaluate the interactions of these spinal processes we performed in vitro-experiments, animal studies and clinical investigations on the compatibility and antispastic efficacy of spinally administered opiates and benzodiazepines. Preclinical studies on tissue- and CSF-tolerance of different benzodiazepines (pH, tonometry, turbidimetry, histological findings in animals) are in favour of midazolam, a water-soluble compound, which is active against pharmacologically induced spasms in animals (strychnine application in cats with chronical catheterization of the subarachnoid space) after lumbar intrathecal injection. Using an appropriate dosage of intrathecal midazolam selective blockade of spasticity of the hind legs may be demonstrated with integrated EMG. Clinical investigations (neurological assessment using rating scores for spasticity) in 16 patients, including a double-blind comparison of epidural morphine or midazolam, indicate that both drugs are effective against spinal spasticity of different origin. Efficacy of spinally applied agents depends on the severity of spasms and on the duration and extent of systemic pretreatment.

Animals↗

[Intra- and postoperative interactions between the 2 opioids fentanyl and buprenorphine].

In order to demonstrate pharmacokinetic and pharmacodynamic interactions between fentanyl and buprenorphine, 3 groups of patients (n = 30) were compared, receiving either fentanyl (0.005 mg/kg b.w.) or buprenorphine (0.01 mg/kg b.w.) or both opioids as analgesic during surgery for disc protrusion. For a period of 4 h haemodynamic parameters were monitored and blood samples were taken for determination of the following concentrations: ADH, ACTH, cortisol, glucose, unbound glycerol, fentanyl and buprenorphine. Blood gas analyses were performed up to 2 h postoperatively. Although in all groups haemodynamic parameters were constant, there was an increase in factors related to operative stress (cortisol, glucose, unbound glycerol, postoperative acidosis) after the combination of both opioids, while postoperative ventilatory parameters in this group were not improved by the partial agonist buprenorphine. Plasma levels were not affected by combined application, except for a slight elevation of buprenorphine concentrations during additional use of fentanyl. Buprenorphine, at least in higher dosages, seems to antagonize analgesia induced by fentanyl, although respiratory depression is even more pronounced. It may be assumed, that with partial agonists the relation of agonistic and antagonistic activity may be different, depending on the dosage used and on the respective pharmacologic effect observed during investigation.

Acid-Base Equilibrium↗

[The relation between risk factors and mortality in aortocoronary bypass operations].

Risk factors related to increased mortality were determined on the basis of 329 aortocoronary bypass operations. They were: (1) emergency surgery, (2) poor left ventricular function, (3) reoperation, and (4) pulmonary hypertension. Angina pectoris, recent myocardial infarction, age over 65 years, obesity, significant systemic disturbances, smoking, arterial hypertension, and sex were without effect.

Age Factors↗

[Benzoyl-kallikrein: kallikrein activity and kinin generation in plasma].

The inactive acyl-derivative benzoyl-kallikrein was prepared from porcine pancreatic kallikrein. By deacylation the enzymatically active kallikrein was generated in plasma from benzoyl-kallikrein demonstrated by means of its amidolytic activity. Benzoyl-kallikrein was protected from being inactivated by plasma inhibitors. Therefore, the kallikrein activity in plasma was higher following incubation of benzoyl-kallikrein than following incubation of the free enzyme. A comparatively high kinin activity was found in rabbit plasma. In human plasma, this effect was prevented by rapid degradation of kinin.

Animals↗

Familial cancer: consequences for the oncological practice.

Pedigree data were systematically collected from patients with newly diagnosed malignant diseases in hospital outpatient services and private offices in Basel. Special efforts were made to verify every tumor diagnosis. The families of 380 adult cancer patients (greater than 16 years; 160 men and 220 women) were evaluated. The mean number of relatives per family tree was 33 (5.9 first degree) in men and 39 (6.4 first degree) in women. There were 29% of families with one, 11% with two, and 6% with three or more first-degree relatives who had cancer. In 6% of the families there was one or more first-degree relative with cancer of the same site as in the proband. Hereditary cancer syndromes were detected in several families. Fifty-four percent of all families showed no tumor occurrence in first-degree relatives. Our program clearly demonstrates that a carefully obtained family history can lead to the recognition of persons with high cancer risk in oncological practice.

Adolescent↗

[The pharmacokinetics of continuous peridural morphine infusion].

In patients with cancer pain treated by continuous epidural opiate infusion (4.5-24 mg morphine per day) via implanted or portable pumps (n = 40) plasma levels of morphine were determined during the postoperative period and during regular refill of the pump systems. Concentrations were between 2.6 and 18.8 ng/ml depending on daily dosage and body weight. There were no signs of accumulation. Concentrations in lumbar CSF measured in some of the patients were 15-20 higher but decreased by 10-20% (in relation to daily dosage) in the course of long-term treatment. This may be induced by reduction in permeability of the dura due to fibrosis within the epidural space after chronicle catheterization. Cervical CSF concentrations (during chordotomy) were about 1/6 to 1/7 of the corresponding lumbar CSF levels. It may be assumed that epidural opiate infusion in spite of low blood levels is accompanied by relevant cerebral opiate actions.

Epidural Space↗

[The tumor markers CEA, TPA and CA 19-9 and ferritin and osteocalcin in follow-up studies in breast cancer].

Radioimmunological determinations of the tumour markers CEA, TPA, CA 19-9, ferritin and also osteocalcin were carried out in 250 patients with ablatio mammae for breast cancer over a follow-up period of at least 1 year. Metastases were detected in 49 of the 250 patients. The normal control group comprised 193 healthy persons. CEA proved to be the most valuable tumour marker, but TPA and ferritin were also significantly elevated in metastatic breast cancer. Combined determination of all 3 parameters gave the best results. Additional measurement of CA 19-9 was helpful in only one of the 49 patients with metastases in whom the 3 other parameter were negative throughout. Hence, determination of CA 19-9 appears unnecessary in breast cancer. In progressive disease the markers generally increased and fell again following successful therapy. In a few cases the opposite was found or no changes were observed. Cases with small local recurrence or an additional carcinoma at an early stage did not exhibit increased marker values as compared to patients without metastases. Not infrequently the increase in markers preceded the manifestation of metastases by several months. Very high concentrations of tumour markers signify a poor prognosis. Osteocalcin was elevated in patients with bone metastases, but not soft tissue metastases. In general, however, it paralleled the serum alkaline phosphatase level.

Adult↗