Biomedical subjects

T Zimmermann

Publications and source records attributed to T Zimmermann.

At least 91 records · Page 5Linked to original sources

PubMed1997

[Intraoperative determination of parathyroid hormone--an alternative to preoperative localization diagnosis].

The results of localization procedures in hyperparathyroidism are not satisfying and amount to 65% for ultrasonography, 63% for CT-scan, 75% for MRI, and 74% for Tc-Mibi scintigraphy. Since 1994, we have performed intraoperative measurement of PTH with a modified immunochemiluminiscence assay in 44 patients. Ten minutes after exstirpation of pathological parathyroid glands, the PTH concentration decreases to less than 40% of the starting PTH level. We think that intraoperative PTH measurement is a rapid and safe method for controlling the success of surgery in HPT and makes preoperative localization procedures unnecessary.

Adenoma↗

PubMed1996

Central projections of Tömösváry's organ in Lithobius forficatus (Chilopoda, Lithobiidae).

Afferents of Tömösváry's organ innervate multiple synaptic sites within the ipsilateral protocerebrum, i.e. neuropil areas proximal to the 2nd optic neuropil, in the dorsolateral protocerebrum, and surrounding the pedunculus of the "mushroom bodies". Sensory input via Tömösváry's organ in Lithobius appears to follow a peculiar neuronal pathway bypassing the deutocerebrum and tritocerebrum which are innervated by many head sensilla in arthropods.

Afferent Pathways↗

PubMed1996

[A new pharmaceutical concept for the therapy of oropharyngeal and esophageal candidiasis with fluconazole].

Administration of fluconazole capsules is of proven worth in the treatment of candidosis of the mucous membranes, particularly in immunocompromised patients. An additional topical effect on the course of oropharyngeal and oesophageal candidosis can be expected when fluconazole is administered as a suspension. For this reason a crossover pharmacokinetic study with 12 healthy volunteers was carried out, in which the concentrations of the antimycotic were measured in saliva and plasma, after oral administration of 100 mg fluconazole as either a capsule or as a suspension. The time-courses of the concentration of fluconazole after the two formulations were very similar in plasma, but significantly different in saliva. The mean Cmax for fluconazole in saliva was 551 micrograms/ml 5 min after ingestion of the suspension and 3 micrograms/ml 4 h after taking the capsule. Over the observation time (0-96 h) the concentration of the antimycotic in saliva was more than 80% higher with the suspension than with the capsule.

Administration, Oral↗

PubMed1996

[Fluconazole: comparison of pharmacokinetics, therapy and in vitro susceptibility of yeasts].

Fluconazole penetrates well into the tissues and body fluids which were examined and achieves rapid equilibration between the different compartments. The pharmacokinetics of fluconazole are independent of the dose after oral or intravenous administration. This finding, together with the drug's slow elimination (t1/2 30 h) facilitate the estimation of the therapeutically effective dosage. The concentrations of fluconazole measured in blood can be extrapolated to the concentrations in tissue (lung, brain, gynecological tissues), body fluids (sputum, saliva, vaginal secretions) and exudates. The concentration of fluconazole in cerebrospinal fluid and in the vitreous humour of the eye is ca. 80% of that in blood. Fluconazole is predominantly excreted in the urine in the unchanged form, which explains the 10 to 20 fold higher concentration of the drug in urine relative to blood. Although this pharmacokinetic profile favours the use of fluconazole in mycotic infections of the urinary tract it also means that the dose of the drug may have to be adapted to lower regimens in the systemic treatment of patients with restricted kidney function. The in vitro and in vivo susceptibility of the yeasts correlates with the concentrations of fluconazole measured in the different compartments of the body.

Antifungal Agents↗

PubMed1996

Screening for cytochrome P450 3A in man: studies with midazolam and nifedipine.

This report describes work directed towards the development of a screening technique for cytochrome P450 3A activity which should be valid for a variety of drugs metabolized by this enzyme. A significant correlation (P < 0.01) was found between the ratio of the plasma concentration of nifedipine to that of its oxidized metabolite and the area under the time curve for the plasma concentration of midazolam. It is suggested that the nifedipine: metabolite ratio might have general predictive value for the metabolism of orally administered cytochrome P450 3A substrates.

Adult↗

PubMed1996

Uptake of azithromycin by various cells and its intracellular activity under in vivo conditions.

The concentrations of azithromycin in polymorphonuclear leukocytes (PMNLs), monocytes, erythrocytes, and plasma were measured in six healthy volunteers after the last treatment of a 3-day regimen of 500 mg once daily. Marked enrichment of azithromycin was found in PMNLs and monocytes. The drug concentrations after the last dose amounted to 114 +/- 43 (mean +/- standard deviation) mg/liter at 12 h in PMNLs and 34 +/- 17 mg/liter at 6 h in monocytes. Fourteen days thereafter, azithromycin was still detectable in the PMNLs at 53 +/- 34 mg/liter and in the monocytes at 1 +/- 2 mg/liter, although the drug was no longer detectable in plasma (< 0.02 mg/liter). Maximum drug concentrations for azithromycin in plasma (0.40 +/- 0.30 mg/liter) and erythrocytes (0.15 +/- 0.05 mg/liter) at 3 h after the last administration were much lower and occurred earlier than those observed in the phagocytic cells. The mean enrichment factors (cellular/extracellular ratios) of azithromycin in phagocytes relative to plasma came to 231 +/- 150 and 3,924 +/- 584 at 3 and 120 h, respectively, for PMNLs and 83 +/- 55 and 523 +/- 285 at 3 and 120 h for monocytes, respectively, after the last dose. The phagocytosis tests with PMNLs separated from the blood of volunteers at various times after the last treatment confirmed the enhanced intracellular activity of these cells against staphylococci.

Administration, Oral↗

PubMed1996

German family study on hereditary breast-ovarian cancer.

An estimated 5% to 10% of all breast and ovarian cancers are attributed to dominant susceptibility genes. Two such genes, BRCA1 and BRCA2, were recently identified. The involvement of these genes was studied in 43 German breast only and breast-ovarian cancer families. All families contained three or more cases of breast or ovarian cancer, with at least two diagnosed under the age of 60 years. Multipoint linkage analysis gave a maximum lod score of 2.13 at the BRCA1 locus under the assumption of genetic heterogeneity, with an estimated 50% of families being linked. Among the 33 breast only cancer and 10 breast-ovarian cancer families, the estimated proportions of linked families were 35% and 75%, respectively. Sixteen families with at least four cases of female breast cancer diagnosed under the age of 60 years, or male breast cancer diagnosed at any age, were analysed for linkage to BRCA2. Positive lod scores at BRCA2 were obtained in six families.

Adult↗

PubMed1996

Interactions of malondialdehyde and 4-hydroxynonenal with rat liver plasma membranes and their effect on binding of prostaglandin E2 by specific receptors.

We investigated effect of aldehydic products of lipid peroxidation, malondialdehyde (MDA) and 4-hydroxynonenal (HNE) on prostaglandin (PG) E2 receptors of liver plasma membranes. The modification of the membranes by MDA diminished PGE2 binding, decreasing receptor affinity for PGE2 and receptor density whereas HNE increased PGE2 binding, enhanced receptor density but did not changed receptor affinity. ESR study showed the decrease of the whole membrane fluidity after modification by MDA whereas HNE lowered membrane fluidity only in the internal zone of lipid bilayer and increased it in the surface area. The possible effects of membrane changes caused by MDA and HNE on PGE2 receptor parameters are discussed.

Aldehydes↗

PubMed1996

Influence of the antibiotics erythromycin and azithromycin on the pharmacokinetics and pharmacodynamics of midazolam.

The pharmacokinetic and pharmacodynamic interaction between azithromycin (CAS 83905-01-5), an azalide antibiotic, and midazolam (CAS 59467-70-8), a short-acting hypnotic agent, was investigated in an open, three-way cross-over study, including erythromycin (CAS 114-07-8) as a positive control. Twelve healthy male and female subjects had standard doses of azithromycin (500 mg o.d. over 3 days), or erythromycin (500 mg t.i.d. over 5 days), or no pretreatment. On the day of the last dose, they ingested 15 mg midazolam. Blood samples were collected and psychometric tests performed. Erythromycin pretreatment (E) significantly changed the pharmacokinetics of midazolam compared to control (C), whereas azithromycin (A) had no such effect. The parameters are summarized as follows: area under the concentration-time curve, AUC (C) 173.8 h.ng.ml-1 vs. (E) 662.7 h.ng.ml-1*+ and (A) 220.0 h.ng.ml-1; concentration maxima (C) 67.2 ng.ml-1 vs. (E) 182.3 ng.ml-1*+ and (A) 86.7 ng.ml-1; elimination half-life (C) 2.21 h vs. (E) 4.85 h* and (A) 2.41 h (* p < 0.05 vs. (C), +p < 0.05 vs. (A)). Pharmacodynamic tests (digit symbol substitution test; critical flicker fusion test; subjective analog scale for rating of alertness; duration of sleep) consistently showed significant differences after erythromycin pretreatment compared to control, but not after azithromycin. Erythromycin, but not azithromycin, causes clinically significant changes in the pharmacokinetics and pharmacodynamics of midazolam.

Adult↗

PubMed1996

[Effect of estradiol valerate and chlormadinone acetate in hormone replacement therapy in postmenopause on Kupperman index, body weight, blood pressure, lipids, enzymes and electrolytes].

Kupperman-index, weight, blood pressure, serum lipids, blood count, thrombocytes, fibrinogen, thrombine time, electrolytes, enzymes, serum proteins, bilirubine and other parameters were studied in 16 healthy post-menopausal women treated for 18 months with 2 mgs estradiol valerate continuously sequentially combined with the antiandrogenic progestogen chlormadinone acetate (CMA) 2 mgs from 1st to 12th every month of treatment. The women were examined after the 1st, 3rd, 6th, 12th, and 18th month during the last 3 days of the progestogen phase, where the CMA had been added to the estradiol valerate for at least 12 days. The combined estradiol-CMA therapy resulted in a significantly reduced Kupperman-index. The total serum cholesterol- and LDLC-levels were also reduced and the HDL-cholesterol and HDLC-cholesterol-quotient increased. Triglycerides, weight, blood pressure, enzymes, and other parameters were unchanged. The positively metabolic effects of estradiol valerate were not altered after the chlormadinone acetate in a sequential regime.

Adult↗

PubMed1996

[Results of elective lymph node excision in melanoma of the trunk].

In our department, between 1979 and 1994, 254 patients, thereof 171 male, 83 female with the average age of 48.2 years underwent surgery because of stage 1 (T2) to stage 3 melanoma that was located on the trunk. Our retrospective analysis was based on those 211 patients who had been followed up by the department of dermatology in our medical center. It was the aim of our study-apart from determining the long-term-prognosis-to find out the number of patients in whom a curative resection could be only achieved by elective lymph node dissection. The 5-year survival rate amounted to 79% for all patients. For patients suffering from stage 1-disease (T2) it was 93%, for those with stage 2-disease 89%, and in case of stage 3-disease 49% respectively. After ELND had been performed, no lymph node metastases were found in patients (0/22) suffering from a T2-tumor. In case of T3-tumors, in 13% (11/82) and in case of T4-tumors in 30% (13/43) lymph node metastases were found. However, only 5 out of 11 patients, with the established diagnosis of a T3-tumor in whom positive lymph-nodes had been found by ELND, and merely 6 out of the 13 patients with a T4-tumor, are still alive after a mean follow-up period of 74 months. We conclude that ELND is not indicated in patients with T2-melanoma. In case of T3- and T4-melanoma, some doubts exist whether patients really benefit from this surgical procedure. Randomized prospective studies are necessary to clarify the importance of elective lymph node dissection.

Adolescent↗

PubMed1996

[The importance of mediastinoscopy for accurate lymph node staging].

The mediastinoscopy (MS) was developed 1959 by Carlens. Since the introduction of computertomography (CT) in the diagnostic of the thorax the MS was no longer used routinely. Because of the introduction of the CT in our clinic we performed only 111 MS between 1981 and 1992, in contrast to 185 MS between 1976 and 1981. No patient died perioperatively. Two patients had to be operated on for bleeding. The sensitivity of the modern CT-scan for a correct preoperative staging of a bronchial carcinoma runs up to 90% and the specifity up to 85%. Therefore a correct preoperative staging can only be reached histologically with the help of a MS. An exception are T1 and T2 tumors because of only 28% mediastinal lymph node metastases. We think that the MS should be performed more often in order to reach a correct, histologically ascertained staging preoperatively.

Carcinoma, Bronchogenic↗

PubMed1996

Interaction between midazolam and clarithromycin: comparison with azithromycin.

A comparative pharmacokinetic and pharmacodynamic investigation was carried out on the interaction between the hypnotic midazolam and 2 different macrolide-type antibiotics, clarithromycin and azithromycin. In an open randomized crossover study of 3 phases 12 healthy volunteers received either clarithromycin (250 mg twice a day for 5 days), azithromycin (500 mg once a day for 3 days) or no pretreatment. On the last day of antibiotic treatment they ingested 15 mg midazolam. Plasma samples were collected for midazolam analysis up to 24 h and pharmacodynamic performance measured by a series of tests up to 12 h. Pretreatment with clarithromycin caused large and statistically significant changes in both the pharmacokinetic and pharmacodynamic parameters of midazolam compared to control. For example, the AUC was increased from 248.84-888.75 hng/ml (factor of 3.57, p < 0.0001) and the mean duration of sleep increased from 135.4 min to 281.3 min (p < 0.05). No statistically significant effect was found with azithromycin in any test. It is concluded that a drug interaction exists between midazolam and clarithromycin which could be of clinical importance. No such effect is present with azithromycin.

Adult↗

PubMed1996

[Primary neuroectodermal tumor (PNET): a rare highly malignant soft tissue tumor in children and young adults].

The PNET is an extremely malignant soft tissue neoplasm resulting from a balanced reciprocal translocation t (11; 22) (q24; q12). Treatment of the undifferentiated small cell tumor is carried out in compliance with the protocol of the soft tissue trail (CWS) from the German Society of Pediatric Oncology. Biopsy-proven diagnosis is followed by primary chemotherapy which leads in 95% of cases to remission. After excision of the remainder of the malignancy, an irradiation of the tumor site and two further sequences of chemotherapy are performed. Between 1986 and 1994, in cooperation with our pediatric and radiotherapeutical colleagues, we treated ten patients. In four patients (median age, 14 years) the PNET originated from the chest wall, in six patients from the paravertebral and retroperitoneal region. Five patients died after 20 months on average, while the remaining five patients are in full remission after 22, 37, 41, 42 and 82 months, respectively.

Adolescent↗

PubMed1996

Examination of the dependence potential of chloral hydrate by oral administration to normal monkeys.

Chloral hydrate (CAS 302-17-0, Chloraldurat), a widely used hypnotic and sedative agent was investigated on its dependence potential in normal Cynomolgus monkeys following oral administration for 6 weeks. Based on the results of a pilot experiment in this study the maximum therapeutic dose was employed (30 mg/kg b.w./day) and an approximately 3-fold higher dose (100 mg/kg b.w./day). The test substance was administered twice a day at interval of 12 h in order to simulate the worst-case situation. In this study there was no indication for any physical dependence potential following a 6-week treatment period with chloral hydrate at dose levels of 2 x 30 and 2 x 100 mg/kg b.w./day, by gavage. In contrast, the positive control substance flunitrazepam (CAS 1622-62-4) in dose level of 2 x 2 mg/kg b.w./day, by gavage possessed a pronounced physical dependence potential. During the withdrawal period flunitrazepam resulted in am impaired motor coordination, tremor, hyperirritability, restlessness and - occasionally - grimacing, an impaired perception, convulsions, emesis and increased body temperature lasting for approximately 7 days after the last application. Symptoms were most pronounced 12 h after the last application (theoretically the next application).

Administration, Oral↗

PubMed1995

[Reactive oxygen species in the pathogenesis of gastrointestinal tumors. A follow-up study].

UNLABELLED: Development and growth of gastrointestinal tumors seems to correlate closely with the formation of reactive oxygen intermediates (ROI). It is known, that oxygen-free-radicals are able to induce a precancerous stage and tumor growth by damaging DNA or changing the protein and lipid structure. To investigate, whether the cellular formation of oxygen-free radicals plays a role in the pathogenesis of colorectal carcinoma, we performed the study presented here. 40 patients with colorectal carcinoma were studied over a period of 6 months (before operation, 10 days after operation, 3 months later, 6 months later). Oxygen-free radicals were determined by chemiluminescence response in the whole blood, in granulocytes and in monocuclear blood cells (MBC). At the same time the trace elements selenium, Copper and Zinc, known to play an important role as antioxidants, were measured. RESULTS: We observed, that the ability of granulocytes for phagocytosis was depleted. However, this effect could be reversed as demonstrated in in vitro stimulation assays. After 6 months the phagocytosis by granulocytes achieved again normal values. Simultaneously a dramatic increase in superoxide-anions generated by mononuclear blood cells was seen. This increase was still obvious after 6 month. Independent of the tumor state selenium deficiency was found in all patients. Since no substitution of selenium was performed after operation, this deficiency was not normalised. CONCLUSION: The ability for phagocytosis and therefore the immune response is reduced in a reversible manner. In addition reactive superoxide-anions, that are able to induce tumors, are formed. This risk is increased in the absence of selenium. Thus, clinical follow-up studies are needed to determine subclinical tumor relapses and to investigate the role of oxidative stress by chemi-luminescence. As consequence of this study selenium substitution seems to be indicated.

Aged↗

PubMed1995

[Decreasing mortality in acute pancreatitis with sodium selenite. Clinical results of 4 years antioxidant therapy].

UNLABELLED: Results obtained from pancreatitis research prove the genesis if free radicals in acute pancreatitis. Xenobiotics, ethanol as well as biliary diseases will induce a deficiency in antioxidants. In antioxidative treatment sodium selenite as a water soluble redox substance represented an alternative. In the middle of the year 1990 the therapy regime was introduced in Rostock, a short time later in Dresden too. The diagnosis was made by CT enhanced by a contrast medium as well as by clinical and paraclinical parameters. CT was repeated after a week. Up to May 31, 1994 there were 245 patients treated in Rostock and 85 patients in Dresden (n = 330). Immediately after making the diagnosis 200 micrograms were given as a bolus, 800 micrograms in the following 24 hours. From the second day on 500 micrograms of selenite were administered daily. In addition, infusions of carbohydrates, electrolytes (no calcium), fluid and analgetics were given. Lavation of the intestine was made three times daily. With a well-timed selenium therapy the rates of letality, complications and operation dropped drastically. In spite of a constant number of patients no patient has died in Rostock since 1993, in Dresden 8 of 85 patients came ad exitum. Complications occurred if the therapy began too late (if patients were administered too late) and in biliary forms. CONCLUSION: An improvement in the prognosis of acute pancreatitis can be achieved if antioxidative selenium therapy with sodium selenite is introduced in time. In rare cases total necroses and complications in organs only occurred in those patients who were admitted to this therapy too late.

Acute Disease↗

PubMed1995

Clinical pharmacological equivalence of a novel FCH-free GTN spray with low ethanol content vs a FCH-containing GTN spray.

The overall therapeutic equivalence of a fluorochlorohydrocarbon (FCH)-free glyceryl trinitrate (GTN) pump spray with a low ethanol content (TL) was investigated relative to an FCH-containing GTN spray (Nitrolingual; R), in terms of: (1) pharmacokinetic bioavailability, (2) pharmacodynamic responses as assessed by digital plethysmography (DPG), and (3) clinical perception upon application. Pharmacokinetically, the time courses of the plasma concentrations of GTN and its dinitrate metabolites, 1,2- and 1,3-GDN, subsequent to the sublingual administration of 0.8 mg GTN showed somewhat lower bioavailability of GTN and its metabolites than to the reference. Pharmacodynamically, the changes in the DPG signals after the application of 0.8 mg GTN with TL were biostatistically equivalent with R (estimated ratio TL/R for the maximum decrease of the ratio between the systolic a wave and c incisure: 0.98; 90% CI: 0.84-1.14; and for the average decrease of the c: a ratio: 0.97; 90% CI: 0.80-1.16). The time of occurrence of the maximum effect of TL was not significantly different from that of R (estimated difference TL-R: -2.25 min; 95% CI:-9.5 min to 2 min). In contrast, after the administration of an FCH-free GTN spray with a higher ethanol content (TH, active control), the effect had a slightly earlier onset (TH-R: -6 min, 95% CI:-9.5 to -2 min) and there was a higher average response (TH/R: 1.12: 90% CI: 0.95 to 1.34). However, TH was consistently judged to cause an extremely unpleasant burning sensation in the mouth and thus was perceived as distinctly different from R. In contrast, TL was well tolerated and could not be distinguished from R.

Adult↗