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Biomedical subjects

C Weiss

Publications and source records attributed to C Weiss.

At least 163 records · Page 9Linked to original sources
PubMed1993

Clinical pharmacokinetics of 5-fluorouracil. Influence of the biomodulating agents interferon, dipyridamole and folinic acid alone and in combination.

The pharmacokinetics of the antimetabolite 5-fluorouracil (5FU, CAS 51-21-8) were investigated under the influence of the biomodulating agents folinic acid (FA), FA combined with dipyridamole (DPM), DPM, interferon-alpha-2b (IFN), and IFN combined with DPM. IFN as well as IFN/DPM cause an enormous increase of the 5FU plasma concentrations resulting in a statistically significant change of the pharmacokinetics. The mean initial plasma concentrations of 5FU are increased at about 143% under the influence of IFN and at 162% under the influence of IFN/DPM. Accordingly, the mean area under the concentration-time curve is elevated at 114% for IFN and at 184% for IFN/DPM. The volume of distribution (IFN - 39%, IFN/DPM - 38%) as well as the total body clearance (IFN - 30%, IFN/IFN - 44%) are lowered distinctly. In contrary, the coadministration of either FA or DPM or FA/DPM to 5FU does not lead to a significant change in the pharmacokinetic profile of 5FU, but also causes higher plasma concentrations. The present results indicate that the coadministration of biomodulators can lead to distinct changes of the 5FU kinetics, but must not be useful in each case.

Aged↗
PubMed1993

Membrane depolarization combined with release of calcium from internal stores does not trigger secretion from PC 12 cells.

The mechanisms underlying catecholamine release from pheochromocytoma (PC 12) cells were examined. Whereas application of 1 microM bradykinin (BK) induced an increase in intracellular calcium ([Ca2+])i), either in medium containing 1.8 mM Ca2+ or in medium prepared without the addition of CaCl2 ("Ca(2+)-free medium"), norepinephrine ([3H]NE) release was induced only in Ca(2+)-containing medium. Similarly depolarization by 50 mM potassium induced [3H]NE release only in 1.8 mM calcium-containing medium. The combination of membrane depolarization (50 mM KCl) with increased [Ca2+]i secondary to BK application in "Ca(2+)-free medium" did not induce catecholamine secretion. It was concluded that Ca2+ entry through calcium channels at the plasma membrane is essential for the activation of catecholamine release. A rise in [Ca2+]i (4-5 times x basal) released from internal stores is not sufficient to trigger secretion from PC 12 cells, either by itself or in combination with membrane depolarization.

Animals↗
PubMed1992

Stress-induced facilitation of classical conditioning.

Stress has been shown to impair subsequent learning. To determine whether stress would impair classical conditioning, rats were exposed to inescapable, low-intensity tail shock and subsequently classically conditioned under freely moving conditions with a brief periorbital shock unconditioned stimulus and a white noise conditioned stimulus. Unexpectedly stressed rats exhibited significantly more conditioned eyeblink responses and the magnitude of their individual responses was also enhanced. These results stand in contrast to the learning deficits typically observed and suggest that stress can enhance the acquisition of discrete conditioned responses.

Acoustic Stimulation↗
PubMed1992

Local hyperthermia enhances cyclophosphamide, ifosfamide and cis-diamminedichloroplatinum cytotoxicity on human-derived breast carcinoma and sarcoma xenografts in nude mice.

Antitumour response and toxicity of locally applied hyperthermia with or without cyclophosphamide, ifosfamide, and cis-diamminedichloroplatinum (cisplatin) have been compared. The model systems were human breast carcinoma (MX1/3) and human sarcoma (S117) grown in nude mice. In order to detect changes of tumour oxygenation intratumoral PO2 and pH were measured before, during and following hyperthermia. In both human tumour lines a monotherapy with one of the cytotoxic drugs or with hyperthermia caused a transient growth delay, while the combination of the same dose of the drugs with hyperthermia (at 43 degrees C for 1 h) resulted in complete tumour remissions. During hyperthermia, in both tumour types oxygenation was improved. Intratumoral pH remained practically unchanged.

Animals↗
PubMed1992

Hyperthermia enhances mitoxantrone cytotoxicity on human breast carcinoma and sarcoma xenografts in nude mice.

In this preclinical in vivo study, we measured antitumor response, local side effects and systemic toxicity of locally applied water-bath hyperthermia given alone or simultaneously with mitoxantrone (3 mg/kg b.w. i.v.; LD 10) on a human derived breast carcinoma (MX 1) or a human sarcoma (S 117) transplanted to female athymic (nude) mice. A single hyperthermia treatment at a tumor temperature up to 43 degrees C for 1 hr caused in both tumor lines only minor tumor regressions and transient tumor growth delay. However, the antitumor effect of mitoxantrone was significantly enhanced by local hyperthermia at 42 degrees C and particularly at 43 degrees C. In both tumor lines complete tumor regressions were achieved only if mitoxantrone was combined with hyperthermia. Undesired side effects and drug toxicity were not enhanced by hyperthermia. According to in vitro data and the results of the present in vivo study mitoxantrone seems to be a good candidate for clinical trials in combination with locoregional hyperthermia.

Animals↗
PubMed1992

Percutaneous absorption of azelaic acid in humans.

Six healthy male volunteers received a single topical treatment with 5 g of an anti-acne cream containing 20% azelaic acid (AzA) onto the face, the chest and the upper back. One week later 1 g of AzA was given orally to the same subjects as aqueous microcrystalline suspension. Following the two treatments the renal excretion of the unchanged compound was measured. Analysis included ether extraction of the urine, derivatization of extract and HPLC with UV detection. After topical application 2.2 +/- 0.7%, and after oral administration 61.2 +/- 8.8% of the dose had been excreted unchanged with the urine. By comparing both amounts, the percutaneous absorption of AzA from the cream was assessed to 3.6% of the dermally applied dose.

Absorption↗
PubMed1992

Exercise-induced symptomatic and asymptomatic myocardial ischemia in patients with severe coronary artery disease: focus on the efficacy and safety of gallopamil.

Symptomatic and asymptomatic episodes of transient myocardial ischemia are well-known risk factors in patients with coronary artery disease. In a single-blind, randomized, and placebo-controlled study, the efficacy and safety of gallopamil was studied during a 1-week treatment period in 25 patients with high-grade coronary artery stenosis and frequent, exercise-induced episodes of myocardial ischemia. Eighteen patients were men, and seven patients were women; the mean age +/- SD was 59 +/- 7 years. After a 1-week run-in period (days 1-7), all patients were treated with gallopamil 50 mg t.i.d. (days 8-14) and placebo t.i.d. (days 15-21) or vice versa. Twenty-four-hour Holter monitoring, exercise testing, and adverse effects were controlled at days 7, 14, and 21. During the run-in period, all patients suffered a mean of 5.9 +/- 2.9 episodes of transient myocardial ischemia, mean ischemic duration was 38 +/- 29 min/day. Gallopamil increased exercise tolerance from 7.9 to 9.8 min (+24%, p < 0.05) and resulted in reduction of the weekly usage of short-acting nitrates by 45% compared to placebo. During 24-h Holter monitoring, mean heart rate at the onset of ST-segment depression increased from 106 to 118 beats/min (p < 0.05). The frequency of daily ischemic episodes was reduced after gallopamil administration from 6.1 to 3.9 episodes/day (-37%, p < 0.05), the total ischemic burden decreased for symptomatic episodes by -54% (p < 0.05) and for asymptomatic episodes by 29% (p < 0.05). Gallopamil modified the circadian distribution of ischemic episodes by modifying the morning peak of transient myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

[The diagnostic imaging of complex breast nodules].

This study was aimed at determining the role of high-frequency (7.5 MHz) US combined with cytology in the diagnosis of complex breast nodules (complex cysts--cystic tumors). The study population included 60 patients presenting with complex breast nodules selected on the basis of US patterns among 3,000 cases. All patients were also submitted to US-guided fine-needle aspiration biopsy (FNAB). Cytology of nipple discharge was always performed when discharge was present (15 cases), mammography was performed in 50 cases and pneumocystography in 10. US allowed the identification of the lesion in all patients and the diagnosis of nature in 73%; with FNAB the figure reached 96.7%. Mammography identified the lesion in 95% of patients, but failed to reveal the complex nature of the nodule. In a small number of cases mammography proved to be a useful complementary tool demonstrating malignant features not recognizable on US images. On the contrary, pneumocystography yielded no further information with respect to US. Diagnostic control was obtained by means of surgery in 30 patients and of clinical-US follow-up in the extant 30 cases. On the basis of their US features the lesions were classified into two groups: I) nodules having a mainly liquid component--i.e., hemorrhagic, septic, multilocular cysts, papillary cystadenoma; II) nodules having a mainly solid component--i.e., solitary intraductal papilloma, intracystic carcinoma, mixed carcinoma, phylloid adenoma, sarcoma. As to the former group, US proved reliable in making a diagnosis in the cases with typical hemorrhagic, septic and multilocular cysts. In the atypical cases, FNAB of the solid component of the nodule was necessary to differentiate irregular clots, thick septa or inflammatory thickening from different conditions. As to the latter group, FNAB of the solid component and/or mammography proved useful in making a diagnosis, even though to this aim US revealed peculiar patterns which were highly suggestive. In our experience, combined US and FNAB are of basic importance in the diagnosis of breast lesions, thus replacing pneumocystography which has been widely employed so far. As regards mammography, its role seems limited to pointing out the peculiar characters of malignancy which could not be demonstrated otherwise.

Adult↗
PubMed1992

[Successful high-frequency current ablation of three accessory conduction pathways in a single session].

A case is presented of a 25-year-old symptomatic male with Wolff-Parkinson-White syndrome and three overt accessory atrioventricular connections which were all diagnosed and ablated during the same session. A discordant preexcitation pattern between delta wave and QRS axis was found on the surface electrocardiogram, indicating the presence of two or more accessory pathways. During atrial pacing the appearance of a changing QRS morphology and alternating delta wave suggested the presence of an additional left-sided pathway. After ablation of a right anteroseptal pathway, a second pathway was found located in the left lateral position and was successfully ablated. The final pathway became evident only after the ablation of the first two and was found to be located in a right midseptal position. This pathway was also ablated during this session. There were no complications and the patient remained asymptomatic during an 11-month follow-up.

Adult↗
PubMed1992

[Echography in gynecologic emergencies].

The authors report their experience with US in gynecologic emergencies through a retrospective study on 105 patients presenting with acute abdomen of suspected gynecologic nature. The series included 3 groups of patients: Group I: 59 patients all submitted to immediate surgery. The following pathologic conditions were observed: ectopic pregnancy (23 cases), torsion or hemorrhage from ovarian cysts (13 cases), pyosalpinx or tubo-ovarian abscess (9 cases), torsion of pedunculated uterine leiomyoma (7 cases), intraperitoneal bleeding from hemorrhagic corpus luteum (6 cases), hematocolpos and hematometra from imperforate hymen (3 cases). Two false positives, not included in this group, resulting from appendicular abscesses and misinterpreted as ovarian, were submitted to surgery in a gynecologic unit. Group II: 19 patients treated with medical therapy for the following conditions: torsion or hemorrhage from hyperstimulated ovary (10 cases), pyosalpinx or tubo-ovarian abscess (9 cases). Group III: 25 patients in whom neither US nor clinical examination revealed positive gynecologic findings. Both US and clinical follow-up were negative in these patients. The study was aimed at evaluating the role of US in identifying both lesion and peritoneal involvement, and in the diagnosis of nature. US proved a valuable tool in the first two diagnostic steps, allowing to confirm/dismiss active pathologic conditions, to indicate the medical/surgical treatment (immediate or delayed), to detect associated pathologies to study with further examinations. As for lesion nature, US alone proved poorly useful if not correlated with an accurate clinical history.

Abdomen, Acute↗
PubMed1991

Classical conditioning selectively increases AMPA receptor binding in rabbit hippocampus.

The NMDA and AMPA receptors have been shown to play critical roles in various forms of synaptic plasticity (learning and memory, long-term potentiation). The present study investigated the involvement of these two receptors in a well-characterized classical conditioning paradigm. Following classical conditioning of the rabbit nictitating membrane the binding properties of these two subclasses of excitatory amino acid transmitter receptors were analyzed in dorsal hippocampi by quantitative autoradiography. [3H] TCP and [3H] AMPA were used to identify the NMDA and AMPA receptors, respectively. The binding of [3H]TCP to the NMDA receptor remained unchanged in all the experimental groups tested. Paired presentations of the conditioned and unconditioned stimuli resulted in increased [3H] AMPA binding to the AMPA receptor in several subfields of the hippocampus, while unpaired presentations had no significant effects. The increase in binding was due to an increased affinity of the low-affinity component of the AMPA receptor. The results support the hypothesis that changes in glutamate receptors participate in the synaptic plasticity involved in certain forms of learning.

Animals↗
PubMed1991

The bradykinin receptor--a putative receptor-operated channel in PC12 cells: studies of neurotransmitter release and inositol phosphate accumulation.

Bradykinin (BK) induced [3H]norepinephrine [( 3H]NE) release and phosphatidylinositol turnover were investigated in PC12 cells. Induction of [3H]NE release by BK is mediated by activation of BK-B2-receptors, as determined using type specific BK receptor antagonists. BK induces [3H]NE release with a half maximal effective concentration of 30 +/- 0.5 nM, and reaches maximal net fractional release of 9.0 +/- 1% with 200 nM BK. The BK-induced release is Ca2+ dependent, reaching maximal release at 1.0 mM Ca2+, is pertussis toxin insensitive (1 microgram/ml), slightly increased by a dibutyryl cAMP (1 mM) and not affected by inhibitors of the cyclooxygenase or lipoxygenase pathways. Voltage-sensitive Ca2+ channel blockers, verapamil (10 microM), nifedipine (10 microM), and omega-conotoxin (CgTx 10 nM), do not block the BK-induced release. However, a considerable inhibitory effect was obtained by divalent cations Co2+ (ED50 = 0.2 mM) and Ni2+ (ED50(2)+ = 1 mM). These results indicate the involvement of a Ca2+ channel in the BK-mediated release which is different from the L- or N-type voltage sensitive calcium channels. Whereas [Ca2+]ex is essential for the BK-induction of catecholamine release, the rise in level of InsP's induced by BK in the presence or in the absence of [Ca2+]ex is similar up to concentration of 1 microM. This indicates that the rise in InsP's induced by BK is not sufficient to cause neurotransmitter release. Moreover, subsequent addition of Ca2+ to BK-stimulated cells in Ca(2+)-free medium yields no release. Hence, no activity triggered by BK alone could be further stimulated by Ca2+ for induction of release.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗
PubMed1991

Developmental myosin heavy chain progression in avian type IIB muscle fibres.

Myosin heavy chain species were investigated during development in avian pectoralis major muscles (type IIB fibres) by high resolution anion-exchange chromatography of the myosin head region, subfragment-1. At 15 days in ovo four distinct fast-type heavy chain species, I, II, III and IV, in order of elution, were identified. By 19 days in ovo, form IV had become predominant and remained the major species through 3-days post-hatch. This form has been named the peri-hatch form. Between 3 and 5 days post-hatch, a second massive change occurred such that by 5 days post-hatch a new species, V, apparent at 19 days in ovo in small amounts, dominated and at 8 days post-hatch was the only heavy chain species present. Form V, which corresponds to that previously identified as the post-hatch form, continued as the major species through 20 days post-hatch and was replaced slowly by the adult form. N-terminal sequencing of CNBr peptides from three subfragment-1 heavy chain species, the peri-hatch (form IV), the post-hatch (form V) and adult, revealed differences in amino acid sequence consistent with the three being products of different genes. These results confirm and extend recent reports of complexity in fast heavy chain expression prior to hatching in the chicken (Hofmann et al., 1988; Van Horn & Crow, 1989).

Amino Acid Sequence↗
PubMed1991

Methodological error and spatial variability of organ blood flow measurements using radiolabeled microspheres.

The quantitative analysis of the spatial variability of organ blood flow by means of radiolabeled microspheres (MS) requires that the methodological variability ("error") of the technique (RDmeth.) is known in each individual organ. Therefore, RDmeth. was quantified (eight to nine nuclides) in 6941 tissue samples from 13 organs of three anesthetized dogs, and the relative importance of errors originating from both the stochastic nature of MS distribution (RDtheo.) and the process of quantitation of MS radioactivity (RDcounting) was assessed under varying conditions (high/low specific MS activity (SAMS); inaccurate separation of gamma spectra; large sample size). At "minimized" methodological error (experiment 2), RDmeth. of samples trapping approximately 375 MS/nuclide was 5.8% and only slightly exceeded RDtheo. (5%). RDmeth. varied in the range 2.7-7.8% in individual organs and contributed little (3.5%) to the organs' observed spatial variability of flow. In contrast, RDmeth.--due to increased RDcounting--considerably exceeded RDtheo. when SAMS was low (experiment 3), overlap of two nuclides' main photopeaks was critical (experiment 1), or counting geometry was inappropriate (pulmonary tissue samples). At the same time, the contribution of RDmeth. to spatial flow variability rose to 7.9% (experiment 3), 26.9% (experiment 1), and 15-23% (lungs). Completely artifactual measurements, as indicated by an extremely high RDmeth. of sample flow, were rarely observed (less than 0.1%). In general, our data suggest that blood flow can be measured reproducibly and with low methodological error using up to 8 nuclides, RDmeth. does not essentially contribute to the observed spatial variability of organ blood flow, and, hence, organ flow variability may be accurately quantified using the MS technique. However, if sources of error as indicated above are present, the practice of using RDtheo. as a measure of RDmeth. (thereby neglecting RDcounting) may notably underestimate true MS error and result in an overestimation of spatial heterogeneity of organ blood flow. RDmeth., therefore, should be quantified separately in each region of interest prior to the onset of a new study.

Animals↗
PubMed1991

Decrease in soluble CD8 antigen levels in splenectomized patients as an index for reduced suppressor/cytotoxic cell activity.

To investigate the effect of splenectomy on lymphocyte subpopulations we monitored changes in serum concentrations of soluble suppressor/cytotoxic (sCD8) and soluble helper/inducer (sCD4) antigen in 11 splenectomized patients. Indications for splenectomy were hereditary spherocytosis in 2, idiopathic thrombocytopenic purpura in 2, gastric carcinoma in 4, Hodgkin's disease in 2 and pancreatitis in 1 patient. Lymphocyte subpopulations were also analyzed by means of conventional immunophenotyping with monoclonal antibodies to CD4 and CD8. We consistently found an early postoperative drop of sCD8 and sCD4 levels within the first week after splenectomy, paralleling changes in the percentages of CD4+ and CD8+ lymphocytes. While alterations of lymphocyte subsets in the peripheral blood were completely reversible and sCD4 levels returned to preoperative values, sCD8 concentrations remained suppressed even 3 months after splenectomy. SCD8 levels at the nadir and those 3 months after splenectomy were significantly lower than preoperative values (P = 0.003, P = 0.149 respectively). Since sCD8 levels reflect suppressor/cytotoxic cell activity, we suggest that suppressor cell activity is reduced in splenectomized patients.

Adult↗
PubMed1991

Effects of hyperthermia and/or hyperglycemia on pH and pO2 in well oxygenated xenotransplanted human sarcoma.

The heat-induced interdependent changes of tumor blood flow, pO2, and pH decisively influence the therapeutic effect of hyperthermia (HT). This fact has induced us to determine simultaneously the frequency distribution of local pO2 values and the intratumoral pH in a xenotransplanted human sarcoma cell line at a normal blood glucose level and under hyperglycemic conditions before, during, and after HT. Two groups, one of 10 and one of 9 congenitally athymic nude rats with a subcutaneously implanted S117 human sarcoma into the right hind paw (mean tumor volume 5.3 cm3) were treated with local waterbath HT (tumor temperature 43 degrees C, 1 hr) alone or in combination with i.p. glucose injections (6 g/kg, 2 hr before the onset of HT). Tumor oxygenation remained improved throughout HT. Tumor pH did not decrease during HT. Hyperglycemia alone elicited a decrease of intratumoral pH and pO2, probably mainly due to hemoconcentration. The additional warming of the tumors (43 degrees C) during hyperglycaemia did not further decrease pO2 and pH. Silver stained sections of the tumors showed only a few very small necrotic areas, even in tumors of volumes up to 8 cm3. Our results indicate a well oxygenated tumor. In contrast to most tumors studied so far, hyperthermia in this tumor induces not only an initial increase of oxygenation but a lasting elevation of mean tumor pO2 for the duration of HT (up to 60 min).

Animals↗
PubMed1991

Isolated serum-free perfused rat kidneys release immunoreactive erythropoietin in response to hypoxia.

The renal glycoprotein hormone erythropoietin (Epo) interacts with erythrocytic progenitors to stimulate their proliferation and differentiation in the bone marrow. The renal O2-sensing mechanism in the control of the synthesis of Epo is still poorly understood. Therefore, the capacity of isolated rat kidneys to produce Epo during hypoxic and anemic perfusion was studied. The kidneys were perfused at a constant perfusion pressure of 100 mm Hg with a substrate-enriched Krebs-Henseleit solution containing 60 g/liter BSA and freshly drawn human erythrocytes. Epo was measured by RIA. When the kidneys were perfused at an arterial pO2 of 720 or 150 mm Hg (hematocrit, 5%), Epo production was very low (0.1-0.2 U/g kidney within 3 h of perfusion). When the arterial pO2 was lowered to 35 or 20 mm Hg, Epo production increased to 0.4 and 0.9 U/g kidney, respectively. The release of Epo during hypoxic perfusion (pO2 35 and 20 mm Hg) was little affected by changes in the hematocrit, i.e. the O2-carrying capacity of the perfusion medium over a wide range (0-40%). These results indicate that the production of Epo in the isolated perfused kidney depends on the availability of O2 and can be modulated by changes in the arterial pO2.

Anemia↗