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Biomedical subjects

M Wolf

Publications and source records attributed to M Wolf.

At least 343 records · Page 19Linked to original sources

Experience with GM-CSF in the treatment of solid tumors.

The efficiency of GM-CSF to reduce myelosuppression after chemotherapy depends on the schedule of administration and the dose of chemotherapy. If conventional chemotherapy doses are given, a seven to ten day administration starting one day after the end of chemotherapy is able to reduce both degree and duration of leucopenia. A later onset is less effective, an earlier one aggravates leuco- and thrombocytopenia. The reduction of myelosuppression is accompanied by a reduction of infection rates and hospitalisation of patients due to these complications. If high-dose chemotherapy is given, GM-CSF does not markedly affect nadir values for leuco- and thrombocytes, but still shortens the duration of leucopenia. This effect is consistently seen after the initial cycles of chemotherapy, but seems to be less pronounced in later cycles. Thus, the growth factor administration allows a treatment intensification mainly by shortening of treatment intervals. Whether these modifications will improve the prognosis of patients with solid tumors is currently being investigated in small cell lung cancer in a German multicenter randomized trial.

Antineoplastic Combined Chemotherapy Protocols↗

Early naming deficits, developmental dyslexia, and a specific deficit hypothesis.

The present research represents the final 2 years of a 5-year longitudinal investigation of (a) confrontation-based, word-retrieval deficits in dyslexic children; (b) the role of vocabulary development in these deficits; (c) the relationship between confrontation naming performance and three carefully defined aspects of reading performance in the general population and in eight dyslexic case studies; and (d) the possible specificity of word-retrieval deficits in dyslexia. Results indicate enduring problems in word-retrieval processes for dyslexic children across the primary grades and into middle childhood. Second, these deficits cannot be explained by simple vocabulary deficits. Third, these results in conjunction with our earlier data consolidate a pattern of differential relationships between specific reading and confrontation naming skills that are based on development and on the level of processes involved. Trends within case studies suggest the more pronounced the retrieval deficit, the more global the reading impairment. And fourth, there appear to be some specific differences in the basis of word-retrieval problems between dyslexic and garden-variety or lower achieving readers. Results are discussed within a speculative framework that implicates problems in timing as a possible predetermining condition in the dyslexias.

Child↗

A randomised double-blind study of high-dose intravenous prochlorperazine versus high-dose metoclopramide as antiemetics for cancer chemotherapy.

High-dose prochlorperazine 0.8 mg/kg administered intravenously 30 min pre and 7 h 30 min post the initial dose of emetogenic chemotherapy was compared to high-dose metoclopramide 2 mg/kg over 20 min every 2 h for five doses starting 30 min prior to chemotherapy in a randomised, double-blind, parallel subjects design study. On the prochlorperazine arm intravenous dextrose placebos every 2 h maintained blinding. Complete suppression of vomiting occurred in 42% on metoclopramide (53% with non-cisplatin regimens) and 36% on prochlorperazine (52% with non-cisplatin-containing regimens) while major responses (2 or less vomits) occurred in 58% on metoclopramide and 54% on prochlorperazine. In patients who vomited after cisplatin, prochlorperazine achieved a significantly shorter duration of vomiting, a median of 5 h compared to 15 h on metoclopramide (P = 0.03). The response rate to prochlorperazine for cisplatin-induced emesis between 12 and 24 h was significantly better than for metoclopramide (prochlorperazine = 0.02). Toxicities were equivalent except for significantly greater sedation and dry mouth on prochlorperazine. Extrapyramidal reactions were recorded equally on both arms but were only severe enough to stop treatment on metoclopramide. The metoclopramide regimen was five times as expensive as prochlorperazine. High-dose prochlorperazine is an active and cost-effective antiemetic.

Adolescent↗

Adrenal masses in lung cancer: sonographic diagnosis and follow-up.

Ultrasound has become an important diagnostic modality in the staging of patients with lung cancer. Between 1980 and 1990, 410 patients with histologically proved lung cancer were evaluated. In 44 patients (11%) an adrenal mass was discovered on ultrasound; in 13 patients it was isolated, and in 31 further evidence of abdominal disease was shown. Sonographic follow-up examinations of adrenal masses showed changes of size in all but 2 patients, and were therefore found to be adrenal metastases. In the 2 patients with isolated and stable adrenal disease, fine-needle biopsy revealed adenomas. Adrenal masses in patients with lung cancer are more likely to be metastatic than benign. The existence of neoplastic adrenal disease can be retrospectively confirmed by changes of size during sonographic follow-up examinations in almost all patients. Histologically verification would only appear necessary in stable adrenal disease and in cases with isolated adrenal disease in which prompt diagnosis affects treatment decision.

Adrenal Gland Neoplasms↗

Levels of expression of the mdr1 gene and glutathione S-transferase genes 2 and 3 and response to chemotherapy in multiple myeloma.

We have quantitated the levels of mRNAs in bone marrow samples from patients with multiple myeloma of the mdr1 gene (responsible for the Multidrug Resistance phenotype) and for two of the glutathione S-transferase gene, GST-2 and GST-3 (which can also inactivate a wide variety of cytotoxic drugs) and examined the relationship between the levels of expression of these genes and response to subsequent chemotherapy. From a total of 47 patients, 37 were treated with chemotherapy with 34 evaluable for response. Twenty-nine of the patients treated had not received any treatment prior to the marrow sampling while eight had previously received chemotherapy. Patients who failed to respond to initial chemotherapy had significantly higher levels of mdr1 than patients who responded (P = 0.01). In the total myeloma patient data set, mRNA levels for mdr1 and GST-2 were significantly correlated (Spearman rank correlation coefficient (r) = 0.54, P = 0.0004) as were expression levels of GST-2 with GST-3 (r = 0.43, P = 0.017). GST-3 and mdr1 levels were more weekly associated (r = 0.16, P = 0.4). These data would suggest a significant relationship between failure of chemotherapy in multiple myeloma patients and increases in expression of the mdr1 gene together with other genes whose products will generate additional mechanisms of resistance to chemotherapeutic agents.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Preclinical and clinical experience with cisplatin and carboplatin and simultaneous radiation in non-small cell lung cancer.

Preclinical experiments with cisplatin and carboplatin showed radiosensitizing capability for these drugs against non-small cell lung cancer (NSCLC) cell lines and phase II clinical investigations were undertaken in patients with stage IIIA/B NSCLC. In the first trial, cisplatin 20 mg/m2 was infused on the first day of every treatment week, followed in about 1 hour by radiotherapy. Radiotherapy was given in single daily 2-Gy doses 5 days a week for 3 weeks, and, after a 2-week interval, for an additional 2 weeks. There were 5 complete responses (CRs) and 15 partial responses (PRs), while 6 patients had no change and 4 progressive disease, for a 67% overall response. Median survival was 14 months; the 2-year survival rate was 20%. To investigate the maximum tolerated dose of carboplatin, escalating doses were given on day 1 of each treatment week; simultaneous radiotherapy was administered as in the cisplatin study. Drug doses began at 100 mg/m2 and were increased by increments of 10 or 20 mg/m2 to a maximum of 200 mg/m2, with 5 patients treated at each dose level. Dose escalation was to stop when 3 of 5 patients developed intolerable World Health Organization (WHO) grade 3 myelosuppression. No grade 3 or 4 leukopenia occurred at carboplatin doses less than or equal to 140 mg/m2. Grade 3 leukopenia was seen in only 1 patient from the groups receiving 150, 160, or 180 mg/m2. Of the 35 patients evaluable thus far, 1 achieved CR and 18 PR, while 10 had no change and 6 progressive disease despite treatment, for a 54% overall response rate. Response rate in patients with stage IIIB disease was 48%.(ABSTRACT TRUNCATED AT 250 WORDS)

Carboplatin↗

Human CC10, the homologue of rabbit uteroglobin: genomic cloning, chromosomal localization and expression in endometrial cell lines.

Human and rat cDNAs to Clara Cell 10 kDa protein (CC10) have been previously isolated. Comparison of the amino acid sequences showed that CC10 is homologous to rabbit uteroglobin. Here we present further evidence that human CC10 is the human counterpart of rabbit uteroglobin. We have isolated the gene and have mapped its genomic localization to chromosome 11q11-qter. Sequence analysis of the 5'-flanking region reveals that the homology between the human and the rabbit gene starts at the first exon/intron boundary and extends up to -1.4 kb. A second region of 0.74 kb from -1.77 to -2.51 kb in the human 5'-flanking gene region is homologous to rabbit sequences that include four progesterone receptor binding sites which have been implicated in progesterone regulation of rabbit uteroglobin gene expression in endometrium. Sequence alignment of this region on the nucleotide level shows that only two weak progesterone receptor binding sites are partially conserved. In addition, close inspection of the human and rabbit promoters reveals that the estrogen responsive element and two recently identified cis elements of the rabbit promoter located between -177 and -258 bp are also absent in the human uteroglobin promoter. Despite these differences in the 5'-flanking regions of the genes, we report that the human uteroglobin mRNA is expressed in a human cell line of endometrial origin indicating that human uteroglobin is expressed in the uterus like its rabbit homologue. Thus, it appears that human uteroglobin is not only a marker for lung Clara cells but also an endometrial differentiation marker.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Clumping of lymphoma cells in peripheral blood induced by EDTA.

A peripheral blood smear from a patient with probable splenic lymphoma with villous lymphocytes (SLVL) showed clumping of lymphoma cells. The clumping was not seen in films made from unanticoagulated blood, and has not been previously described in lymphomas. The patient also had metastatic prostatic adenocarcinoma for 30 months before lymphoma was diagnosed and the clumped cells posed diagnostic problems.

Adenocarcinoma↗

Carboplatin and simultaneous radiation in the treatment of stage IIIA/B non-small cell lung cancer.

The radiosensitizing properties of carboplatin were investigated in preclinical and clinical studies. In human non-small cell lung cancer (NSCLC) cell lines (EPLC 65 H and LCLC 97 TM1) combined carboplatin and radiation therapy was superior to chemotherapy or radiotherapy alone, indicating the existence of additive effects for both treatment modalities. In a subsequent clinical phase II trial, escalating doses of carboplatin were given concurrently with radiation to patients with stage IIIA/B NSCLC. Radiotherapy was given in daily doses of 2 Gy, 5 days a week, during weeks 1-3 and 6 and 7. Carboplatin was given on day 1 in weeks 1-3 and 6 and 7. The starting dose level was 100 mg/m2, followed by dose escalations to 120, 130, 140, 150, 160, 180, and 200 mg/m2. Five patients were to be treated at each dose level until intolerable toxicity (World Health Organization grade 3 or 4 leukopenia) occurred in 3 of the 5. To date, 34 patients have been entered into the study. Toxicity was mild and, even at the 180-mg/m2 dose level, no severe myelosuppression was observed. Thus, the maximum tolerated dose of carboplatin has not yet been reached. Preliminary analysis of response and survival shows an overall response rate of 53% and a median survival of 10 months. Patients receiving higher carboplatin doses (140-160 mg/m2) survived longer than patients who received lower doses (100-130 mg/m2). These preliminary results indicate that combination carboplatin and radiation therapy is a well-tolerated, active regimen in patients with locally advanced NSCLC. Splitting carboplatin administration may reduce its hematologic toxicity.

Carboplatin↗

[Ergotism and ischemia of the limbs].

Clinical ergotism as seen today results almost exclusively from the intake of ergotamine tartrate in the treatment of migraine headache. Vasospasm of peripheral arteries is the leading clinical picture. Besides the formation of collaterals and a secondary thrombosis, the vasospasm is one of the specific findings in arteriography. Early diagnosis and withdrawal of the medication makes complete restitution possible. In all other cases intraarterial or intravenous infusion of sodium nitroprusside has turned out to be the most effective therapy. Balloon dilatation or operative intervention are an alternative therapy in those cases, where amputation of the limbs seems to be necessary.

Adult↗

[Sonography during the pregnancy of sheep. I. Fetometry for the determination of the stage of gestation and prediction of the time of parturition].

Transrectal and transcutaneous ultrasonography was performed on 187 pregnant Merino ewes to measure the growth of fetal parameters (fetometry) such as the diameters of the eye, braincase and trunk, the width of one rib with its intercostal space and the crown-rump-length (CRL). In the ewes, cross and longitudinal diameters of the intrauterine lumen around the embryo and fetus were determined. Trunk diameter and crown-rump-length of embryos and fetuses were sonographically determined from Day 26 and size of eyes, braincase and ribs were measured from Day 52 to 66 of gestation. Embryonic resp. fetal parameters and uterine diameters showed almost linear growth rate. Relationship between the measured parameters and days of pregnancy is described by regressions and correlation coefficients. Correlation coefficient between gestational stage and the diameter of the trunk was very narrow (r = 0.98) and between gestational stage and the crown-rump-length resp. eye diameter equalled 89% (r = 0.89). These fetal parameters are appropriate to assess gestational age and growth of ovine fetuses. It can be concluded that sonographic fetometry in the ovine can be valuable for the evaluation of fetal development, the estimation of gestational age and the prediction of parturition dates.

Animals↗

Characterization of insulin-like growth factor receptors in human thyroid tissue.

We have characterized the binding of 125I-IGF-I and 125I-IGF-II to plasma membranes purified from human thyroid tissue. IGF binding was time- and temperature-dependent. At 4 degrees C, maximal specific binding of 125I-IGF-I was 17.3 +/- 2.5% and of 125I-IGF-II was 8.8 +/- 2.0% (mean +/- SD/60 micrograms membrane protein). 125I-IGF-I binding was inhibited completely by unlabeled IGF-I, IGF-II, insulin, and the type-I IGF receptor monoclonal antibody, alpha IR-3. 125I-IGF-II was inhibited completely by unlabeled IGF-II and nearly completely by IGF-I. 125I-IGF-II binding also was inhibited significantly by insulin, suggesting that much or all of the IGF-II was bound to the type-I IGF receptor. Scatchard analysis revealed a single class of binding sites with a Kd of 6.0 +/- 4.2 x 10(-10) M for IGF-I binding and 5.7 +/- 1.3 x 10(-10) M for IGF-II binding. IGF-I binding was inhibited by a variety of salts in a dose-dependent manner, calcium and magnesium salts being more effective than sodium or potassium salts. Affinity crosslinking of 125I-IGF-I and -II showed clear evidence only for type-I IGF receptors. Thus, a crude plasma membrane fraction of human thyroid tissue expresses predominantly type-I IGF receptors.

Affinity Labels↗

Severe respiratory syncytial virus pneumonia after autologous bone marrow transplantation: a report of three cases and review.

Three patients with acute leukemia who underwent autologous bone marrow transplantation (BMT) in complete remission, developed a severe respiratory syncytial virus (RSV) pneumonia, which was fatal in two. Identification of RSV was made on the products of bronchoalveolar lavage by direct immunofluorescence. As already described by others, the initial course of RSV infection varies, depending on whether it occurs sooner or later after BMT with a better prognosis in the latter situation. Treatment consists of aerosolized ribavirin. Infection by RSV is caused by manual contact with infected persons and contaminated surfaces. The severity of lung RSV infection in the course of BMT suggests the need for prophylactic measures in addition to standard isolation precautions.

Acute Disease↗

Evaluation of Win 49,596, a novel steroidal androgen receptor antagonist, in animal models of prostate cancer.

A series of experiments were conducted to evaluate the effects of Win 49,596, a novel steroidal androgen receptor antagonist, in animal models of prostate cancer. In the first experiment, oral administration of Win 49,596 at doses of 30, 100, or 300 mg/kg/day for 28 days inhibited (P less than 0.05) the growth of the androgen-sensitive PAP variant of the Dunning R-3327 prostatic carcinoma in intact male rats relative to intact controls. The degree of inhibition at 100 and 300 mg/kg/day Win 49,596 was similar (P greater than 0.10) to that observed in castrate controls as well as in intact rats administered the nonsteroidal androgen receptor antagonist flutamide orally at 15 mg/kg/day. Castration as well as treatment with either Win 49,596 or flutamide also decreased (P less than 0.05) the weight of the prostate in tumor-bearing animals. Additional studies were conducted to determine the effect of Win 49,596 on the growth of the androgen-dependent PC-82 human prostatic carcinoma xenografted into athymic nude male mice. Oral administration of Win 49,596 at 30, 100, or 300 mg/kg/day for 35 days inhibited (P less than 0.05) tumor growth relative to intact controls. The degree of tumor inhibition was similar to that observed in intact male mice administered the nonsteroidal androgen receptor antagonist flutamide orally at 30 mg/kg/day but was less than that observed following castration. Ventral prostate weights were also reduced (P less than 0.05) in castrate mice as well as in intact mice administered either Win 49,596 or flutamide. In the last experiment, at equivalent total daily dosages of either 150 or 300 mg/kg/day Win 49,596, twice a day (BID) dosing was more effective than once a day (SID) dosing in inhibiting tumor growth. The inhibitory effects of Win 49,596 at 150 mg/kg BID on tumor growth were similar to those observed following castration. Although Win 49,596 treatment reduced (P less than 0.05) ventral prostate weights relative to intact controls, there was no difference (P greater than 0.10) between SID vs. BID dosing. Based on the results of these studies and subject to further testing, Win 49,596 may have utility in the treatment of hormonally dependent metastatic prostate cancer in humans.

Administration, Oral↗

Phase II evaluation of amonafide in renal cell carcinoma. A Southwest Oncology Group study.

Twenty four patients with advanced renal cell carcinoma were treated in a phase II trial with amonafide 300-450 mg/m2/day on days 1-5 every 21 days. There were no responders, 6 patients had stable disease, 14 experienced progressive disease and 4 were assumed to be non-responders as no evaluation was performed. There were no fatal toxicities although 8 patients had grade 3 or 4 granulocytopenia, 1 patient had grade 4 thrombocytopenia. Other toxicities included grade 3 diarrhea in 1 patient, grade 3 myopathy in 1 patient, severe nausea and vomiting in 1 patient and a facial rash, possibly a hypersensitivity reaction, in 1 patient. The median survival is 7.5 months. At this dosage and schedule, there is no evidence that amonafide has meaningful anti-tumor activity in patients with advanced renal cell carcinoma.

Adenine↗