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Biomedical subjects

C Martini

Publications and source records attributed to C Martini.

At least 91 records · Page 5Linked to original sources
PubMed1997

Radiotherapy in stage IIA and IIB testicular seminoma with reduced portals: a prospective multicenter study.

PURPOSE: A prospective multicenter study was carried out to estimate the treatment outcome of radiotherapy in Stage II seminoma after the application of modern staging and radiotherapy techniques. The lower margin of the iliac field was positioned on the upper rim of the acetabulum to reduce the amount of scattered irradiation to the remaining testicle. METHODS AND MATERIALS: The study was carried out in 25 centers in Germany. Patients with pure seminoma, negative AFP-values, and retroperitoneal lymph node metastases of less than 5 cm in diameter were entered into the study. All patients received a ventrodorsal opposed field irradiation of the para-aortic and the ipsilateral iliac lymph nodes. The fields extended from the top of the 11th thoracic vertebra to the top of the acetabulum. Patients in Stage IIA (lymph nodes <2 cm ) received 30 Gy, and patients with Stage IIB (lymph nodes between 2 and 5 cm) 36 Gy total dose. RESULTS: 39 patients in Stage IIA and 19 patients in Stage IIB were evaluated. After a median observation time of 37 months all patients are alive and disease free. Recurrence free survival in stage IIA was 100%. Two patients in Stage IIB experienced a recurrence 10 and 17 months after the end of radiotherapy. The actuarial recurrence free survival estimate in Stage IIB was 94.1% for 1 year and 87.4% for 2 years. One recurrence in Stage IIB occurred in the mediastinum, one in the mediastinum, and one the lung. Both patients could be salvaged by chemotherapy. There were no pelvic recurrences. The treatment was well tolerated, with nausea being the most common side effect (56.9% Grade 1, 15.5% Grade 2, and 8.6% Grade 3). Diarrhea occurred in 15.5% (Grade 1), 15.5% (Grade 2), and 5.2% (Grade 3) of the patients. CONCLUSIONS: The outcome of para-aortic and ipsilateral iliac irradiation in Stage IIA/B testicular seminoma is excellent with the currently available staging methods and treatment facilities. The treatment is well tolerated. The lower margin of the iliacal field can be placed at the acetabulum.

Adult↗
PubMed1997

Chemical modifications of striatal A2A adenosine receptors: a possible role for tyrosine at the ligand binding sites.

A2A adenosine receptors were examined in bovine striatal membranes following exposure to tetranitromethane (TNM) which modifies tyrosine and cysteine residues. TNM (0.05-0.5 mM) treatment caused an irreversible, concentration-dependent decrease in the binding activity of the selective A2A agonist [3H]CGS 21680. Protection studies showed that TNM inactivation could be prevented by the adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA) and by the antagonist xanthine amine congener (XAC), suggesting that TNM modified residues at the ligand-binding sites. Scatchard analysis of the binding data showed that 0.15 mM TNM decreased the [3H]CGS 21680 Bmax value from 447 +/- 39 to 273 +/- 21 fmol/mg of proteins without any significant change in the Kd values (13.5 +/- 1.4 and 14.7 +/- 1.5 for control and treated membranes, respectively). We carried out a series of successive chemical modifications with the reducing agent dithiothreitol (DTT), which indicated that the residues modified by TNM, under our experimental conditions, are tyrosine residues and not cysteine residues.

Adenosine↗
PubMed1997

Beta cell response to oral glimepiride administration during and following a hyperglycaemic clamp in NIDDM patients.

The aim of the present study was to assess the beta cell response to glimepiride, administered orally, during and following a hyperglycaemic clamp in 14 NIDDM patients (7 males), aged 62.5 (St. Dev. 7.7) years with a body mass index of 27.3 (2.8) kg m(-2) and HbA(Ic) of 7.0 (0.7)% at baseline, in a placebo controlled study. All patients were on stable treatment with a second generation sulphonylurea for at least 8 weeks prior to randomization and received placebo (P) or 5 mg glimepiride (G) daily for 7 days and 10 mg prior to a hyperglycaemic clamp (10.9 mmol l(-1) for 60 min, preceded by i.v. insulin infusion to stabilize fasting blood glucose levels at 4.0 mmol l(-1)). The clamp was followed by an observation period of 2 h in 5 subjects and 3.5 h in the next 9 subjects, during which blood glucose and plasma insulin, C-peptide and proinsulin levels were measured at regular intervals to determine the effect of glimepiride on the interaction between changes in glycaemia and plasma levels of beta cell products. Neither G nor P elicited a first phase insulin response. Areas under plasma insulin curve during the 1 h hyperglycaemic clamp were 94.2 (39.5) vs 69.1 (26.5) pmol.h l(-1) in G and P clamps, respectively (p = 0.002). Total areas (AUC) under the plasma insulin curve were 377 (145) vs 271 (113) pmol.h l(-1) in G and P clamps (< 0.05). Total AUCs of C-peptide were 309 (96) and 259 (102 pmol.h.(-1), in G and P clamps, respectively, p = 0.01. Total AUCs of proinsulin were 176 (77) versus 119 (56) pmol.h l(-1) in G and P clamps, respectively, p = 0.004. Five hours after G and P administration blood glucose levels were 4.7) 92.1) mmol(-1) in the G clamp vs 6.2 (1.9) mmol l(-1) in the P clamp (p = 0.001). The number of hypoglycaemic events (blood glucose < 3.0 mmol l(-1)) in the 3.5 h observation period was 3 in G clamps vs 0 in P clamps (p = ns). In conclusion, glimepiride stimulates the second phase insulin and proinsulin secretion. The lowering of blood glucose levels is not accompanied by a commensurate inhibition of the insulin secretion. Further studies are required to compare this new drug with currently available oral hypoglycaemic agents, with respect to glycaemic control and the risk of hypoglycaemia.

Administration, Oral↗
PubMed1997

Peripheral benzodiazepine receptors in isolated human pancreatic islets.

Peripheral benzodiazepine receptors have been shown in some endocrine tissues, namely the testis, the adrenal gland, and the pituitary gland. In this work we evaluated whether peripheral benzodiazepine receptors can be found in the purified human pancreatic islets and whether they may have a role in insulin release. Binding of the isoquinoline compound [3H]1-(2-chlorophenyl-N-methyl-1-methyl-propyl)-3- isoquinolinecarboxamide (13H]PK-11195) a specific ligand of peripheral benzodiazepine receptors, to cellular membranes was saturable and Scatchard's analysis of the saturation curve demonstrated the presence of a single population of binding sites, with an affinity constant value of 9.20 +/- 0.80 nM and a maximum number of binding sites value of 8913 +/- 750 fmol/mg of proteins. PK-11195 and 7-chloro-1,3-dihydro-1-methyl-5-(p-chlorophenyl)-2H-1,4- benzodiazepine-2-on (Ro 5-4864) significantly potentiated insulin secretion from freshly isolated human islets at 3.3 mM glucose. These results show the presence of peripheral benzodiazepine receptors in purified human pancreatic islets and suggest their role in the mechanisms of insulin release.

Benzodiazepinones↗
PubMed1997

Apoptotic DNA fragmentation, and its in vitro prevention by nicotinamide, in lymphocytes from HIV-1-seropositive patients and in HIV-1-infected MT-4 cells.

Apoptosis seems to play an important role in the decline of CD4+ T-cells in patients infected with HIV-1. Moreover, extensive interest in apoptosis comes from the observation that it correlates both with the progression and the severity of HIV-1 infection. A cross-sectional study was made to evaluate whether such correlation may also extend to the early phases of ex vivo apoptosis, after 20 h of culture. DNA fragmentation, a parameter associated with apoptosis, was evaluated with the terminal deoxynucleotidyl-transferase-mediated dUTP nick end labelling (TUNEL) technique, which preferentially labels apoptosis in comparison to necrosis. The results obtained indicate that a negative correlation exists between the proportion of lymphocytes exhibiting DNA strand breaks and the absolute number of CD4+ T-cells per microliter. DNA fragmentation was significantly higher in patients with AIDS or advanced HIV-1 infection as compared to asymptomatic patients or seronegative individuals. No significant difference was found in relation to antiretroviral therapy. Furthermore, the addition of nicotinamide to the cultures significantly reduced DNA fragmentation of both in vitro HIV-1-infected MT-4 cells and lymphocytes from six HIV-1-seropositive individuals. The results of this study confirm that DNA fragmentation, as an early marker of apoptosis, correlates with the severity of HIV-1 infection and suggest that nicotinamide may be involved in the modulation of HIV-1-related apoptosis.

Adult↗
PubMed1997

Pain due to epidural tumor in cancer patients. Report of two cases and differential diagnosis.

The cases of two patients with inguinal pain as the only symptom of a T12 metastatic lesion is reported. The patterns of pain referrals from tumor lesions to the spine, epidural space, and spinal cord are reviewed. Focal back pain and pain reported in a distal distribution can both be associated with epidural or cord disease. The differential diagnosis of back pain in patients with cancer can be difficult but may be crucial in differentiating important neurological complications of systemic neoplasms.

Adenocarcinoma↗
PubMed1997

Intravenous pamidronate treatment in osteogenesis imperfecta.

Three children with osteogenesis imperfecta, severe osteopenia, and repeated fractures were treated with cyclic infusions of aminohydroxypropylidene bisphosphonate (pamidronate) for a period ranging from 22 to 29 months. A clear clinical response was shown, with a striking reduction of new fracture episodes and a marked improvement in the quality of the patients' lives. Bone mineral density increased significantly in two patients, and linear growth continued along the percentile at the start of treatment. There were no adverse effects of note during treatment, and further studies are warranted.

Bone Density↗
PubMed1997

Recovering optic neuritis during systemic cisplatin and carboplatin chemotherapy.

INTRODUCTION: We describe bilateral optic neuropathy in a patient affected by ovarian carcinoma treated with cis-platin 160 mg/m2 and carboplatin, 640 mg/m2. The patient was followed for 1 year, when recovery appeared. The few previous descriptions of CDDP optic nerve toxicity did not report recovery. METHODS: Computerized visual field, visual evoked potentials, pattern electroretinograms, full field flash electroretinograms were recorded during follow-up. RESULTS: Optic neuritis appeared 13 weeks after cis-platin discontinuation, with right eye central scotoma; 2 days later the patient became bilaterally blind. Visual evoked potentials were initially absent, reappeared, with delayed latencies to left eye stimuli at 6 months, in both eyes at 9 months. At 1 year delayed VEPs were recorded with right eye stimuli, normal VEPs were recorded for left eye. CONCLUSION: Cis-platin can induce delayed optic neuritis, that can recover in 1 year.

Antineoplastic Agents↗
PubMed1997

[Prognostic factors in breast carcinoma with negative axillary lymph nodes].

Conventionally, tumor size, axillary lymph nodes status, histologic type and grading, proliferative activity, steroid receptors have been used to predict the natural history of breast cancer. In node-negative patients with breast cancer it is most important to identify biological markers that can predict the risk of systemic relapse. These features have been used to allow selection of the best treatment. In this paper we describe the prognostic significance of new tumoral markers in breast cancer patients without axillary involvement. We analyze the prognostic role and the correlation with response to treatment of these parameters: ploidy, oncogenes, p53, epidermal growth factor receptor and cathepsin D.

Biomarkers, Tumor↗
PubMed1996

Synthesis, structure-activity relationships, and molecular modeling studies of N-(indol-3-ylglyoxylyl)benzylamine derivatives acting at the benzodiazepine receptor.

A number of N-(indol-3-ylglyoxylyl)benzylamine derivatives were synthesized and tested for [3H]flunitrazepam displacing activity in bovine brain membranes. Some of these derivatives (9, 12, 14, 15, 17, 27, 34, 35, 38, 41, and 45) exhibited high affinity for the benzodiazepine receptor (BzR) with Ki values ranging from 67 to 11 nM. The GABA ratio and [35S]-tert-butylbicyclophosphorothionate binding data, determined for the most active compounds, showed that they elicit an efficacy profile at the BzR which depends on the kind of substituent present on the phenyl ring of the benzylamine moiety. Moreover, lengthening (propylamine derivatives 1-3) and shortening (aniline derivatives 46-54) of the distance between the phenyl ring and the amide group of the side chain gave compounds with a drastically lower binding potency. The biological results are discussed in the light of a recently proposed pharmacophore model and compared, by molecular modeling studies, with those obtained from effective BzR ligands.

Animals↗
PubMed1996

Characterization of peripheral benzodiazepine receptors in purified large mammal pancreatic islets.

In this work, we evaluated the biochemical properties of peripheral benzodiazepine receptors (PBRs) in the porcine endocrine pancreas and their role in insulin release. Binding of [3H]1-(2-chlorophenyl-N-methyl-1-methyl-propyl)-3-isoquinolinecarboxa mide ([3H]PK-11195), a specific ligand of PBRs, to islet membranes was saturable and Scatchard's analysis of saturation curve demonstrated the presence of a single population of binding sites, with a dissociation constant (Kd) value of 4.75 +/- 0.70 nM and a maximum amount of specifically bound ligand (Bmax) of 4505 +/- 502 fmol/mg of proteins. The pharmacological profile of PBRs was determined as the ability of PK-11195 and several benzodiazepine compounds to displace [3H]PK-11195 from these binding sites. The rank order of potency yielded the following affinity results: PK-11195 > 7-chloro-1,3-dihydro-1-methyl-5-(p-chlorophenyl)-2H-1,4-benzodiazepine-2 -on (Ro 5-4864) > diazepam > or = flunitrazepam >> flumazenil. Secretion studies demonstrated that PK-11195 (1 and 10 microM) and Ro 5-4864 (10 and 50 microM) significantly potentiated insulin secretion from freshly isolated porcine islets at 3.3 mM glucose. This potentiating effect was not observed at 16.7 mM glucose concentration nor by the addition of clonazepam. These results show the presence of PBRs in purified porcine pancreatic islets and suggest an implication of PBRs in the mechanisms of insulin release.

Animals↗
PubMed1996

Serum cytokine profiles in acute primary HIV-1 infection and in infectious mononucleosis.

Serum cytokine profiles, T-cell subsets, and general parameters of immune activation were evaluated in 15 patients with acute primary HIV-1 infection, and compared with those obtained from 18 patients with acute primary Epstein-Barr virus (EBV) infection and from 18 control subjects in order to elucidate possible defects of immune response to HIV in early phases of virus-host interaction. Mean CD4+ cell count, serum concentrations of interleukin (IL)-2, IL-4, soluble IL-2 receptor (sIL-2R), tumor necrosis factor (TNF)-alpha, 5'-neopterin, and beta 2-microglobulin were significantly lower in acute HIV-1 infection than in EBV infection. Both acute HIV-1 and EBV infections were characterized by significantly higher mean CD8+ cell count and soluble CD8 antigen (sCD8) levels compared to control subjects, while acute HIV-1 infection was accompanied by the highest interferon (IFN)-gamma serum concentrations. In primary HIV-1 infection, significant impairment of CD4+- mediated T-helper function may lead to viral escape and persistence of infection despite an early and vigorous CD8+ T-lymphocyte activation.

Acute Disease↗
PubMed1996

Vinorelbine: an active, non cross-resistant drug in advanced breast cancer. Results from a phase II study.

PURPOSE: To evaluate efficacy and toxicity of vinorelbine and to investigate its cross-resistance with other current drug treatments for metastatic breast cancer. PATIENTS AND METHODS: From July 1992 to December 1993, 57 histologically proven breast cancer patients entered this Phase II study. Patients were stratified according to their status of previous treatment, namely, no prior chemotherapy or relapse more than 12 months since the end of adjuvant chemotherapy (Group A) and other patients (Group B). RESULTS: Fifty three patients were evaluable for response, 27 in Group A and 26 in Group B. All patients were evaluable for toxicity. Vinorelbine was initially administered at the dose of 30 mg/sqm weekly by i.v. infusion in 100 ml of normal saline over 20 minutes. A frequency analysis of drug administration in the first 20 cases revealed two main treatment periodicities, corresponding to one week and to three weeks. Thereafter the drug was administered at 30 mg/sqm on day 1 and 8, every 3 weeks. With the new drug schedule, the mean dose intensity increased from 19.7 to 21.1 mg/sqm per week. Overall, an objective response rate of 47% (95% C.I. 33%-61%) was documented. Four patients achieved complete response (7%, CI: 2%-18%) and 21 partial response (40%, CI: 26%-54%). Fifty nine percent of patients in Group A and 35% in Group B showed objective tumor response. The analysis of response rate in previously treated patients failed to show evidence of cross-resistance with vinorelbine. Main side effects, i.e. neutropenia, local pain, and gastrointestinal and flu-like symptoms, were moderate and short lasting. CONCLUSION: Vinorelbine has clinically significant activity in metastatic breast cancer, and no cross-resistance with prior anthracyclines and CMF treatments. The drug schedule of 30 mg/sqm iv bolus on day 1 and 8 every 3 weeks was found effective and tolerable.

Adult↗
PubMed1996

Characterization of a voltage-dependent L-type calcium channel from rabbit and turtle brain.

The binding of [3H]nitrendipine to membrane preparation from turtle and rabbit brain was studied. A single population of [3H]nitrendipine binding sites was detected in both species. [3H]nitrendipine bound with high affinity to brain membrane from both rabbit and turtle, revealing a significant population of binding sites (K(D) values of 0.55 +/- 0.05 nM and 0.56 +/- 0.04 nM and Bmax values of 122 +/- 11 and 275 +/- 18 fmol/mg of protein, respectively). Displacement studies showed a similar order of potency of various unlabeled ligands against [3H]nitrendipine both in rabbit or in turtle: nitrendipine > nifedipine >or= nicardipine >> verapamil >or= diltiazem. Our results show that a two fold increment of [3H]nitrendipine binding sites exists in the turtle brain respect to the rabbit.

Animals↗
PubMed1996

Binding of beta 1-adrenoceptor antagonist [3H]CGP 26505 in rat cerebral cortex and sinus atrial node.

Specific beta 1-adrenoceptors antagonist [3H]CGP 26505 binding was characterized in rat cerebral cortex and heart sinus atrial node. In both tissues [3H]CGP 26505 binding was maximal at 25 degrees C, it was specific, saturable and protein concentration dependent. Scatchard analysis of saturation isotherms of specific [3H]CGP 26505 binding in cerebral cortex showed that [3H]CGP 26505 binds a single class of high affinity sites with a dissociation constant (KD) of 1 +/- 0.3 nM and a maximal number of binding sites (Bmax) of 40 +/- 2 fmol/mg of protein. In sinus atrial node, [3H]-CGP 26505 binds a single class of high affinity sites (KD = 1.9 +/- 0.4 nM, Bmax = 28 +/- 2 fmol/mg of protein).

Adrenergic beta-Antagonists↗
PubMed1996

2,3-Butanedione inactivates the [3H]nitrendipine binding sites, whereas diethylpyrocarbonate does not.

The modification of [3H]nitrendipine binding sites in rabbit brain membranes with 2,3-butanedione and diethylpyrocarbonate was investigated. 2,3-Butanedione, an arginine-specific reagent, causes a dose- and time-dependent decrease in the number of [3H]nitrendipine binding sites without altering its dissociation constant. Scatchard analysis of the binding data shows that 50 mM 2,3-butanedione decreases the binding capacity of [3H]nitrendipine from a control value of 71 +/- 6 fmol/mg of protein to 40 +/- 3 fmol/mg of protein. Complete and selective protection against inactivation is provided by nifedipine. No decrease of [3H]nitrendipine binding occurs when membranes are pretreated with selective histidine reagent diethylpyrocarbonate. The results indicate that arginine but not histidine residue in L-type calcium channel domain in critical for [3H]nitrendipine binding.

Animals↗