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Biomedical subjects

M Wolf

Publications and source records attributed to M Wolf.

At least 19 recordsLinked to original sources

High dose chemotherapy and autologous bone marrow transplantation in advanced Hodgkin's disease.

OBJECTIVE: To present the use of high dose chemotherapy with autologous bone marrow transplantation as salvage therapy for advanced Hodgkin's disease in Australia. DESIGN: A prospective open study for patients whose disease was resistant to conventional treatment. SETTING: The bone marrow transplantation units of four Australian tertiary hospitals. PATIENTS: Seventeen patients (median age 30 years) entered and completed the study. The stage of the disease at initial diagnosis was I or II (seven patients), III (seven patients) and IV (three patients). Histological types were lymphocyte predominant (one), nodular sclerosis (12), mixed cellularity (three) and unknown (one). Therapy before consideration for transplantation included radiotherapy (13), mustine, vincristine, procarbazine and prednisone (MOPP--17 patients) or doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD--13 patients) and other chemotherapy regimens (five). The median interval from diagnosis to transplantation was 29 months (range, 9-178 months). The patient's disease was classified as sensitive (nine) or resistant (eight) to treatment, depending on the response to the most recent course of chemotherapy. INTERVENTIONS: Morphologically normal autologous bone marrow was harvested and cryopreserved. The conditioning regimen given was cyclophosphamide, carmustine and etoposide (14) or busulphan and cyclophosphamide (three). The marrow was then infused. MAIN OUTCOME MEASURES: Remission (complete or partial), disease-free survival and overall survival. RESULTS: Over all, 10 of 17 patients (59%) entered or remained in complete remission and four of 17 (24%) achieved partial remission. The overall actuarial survival at 30 months was 70%. Eight of the nine patients with treatment-sensitive disease (89%) remain disease-free at a median of 22 months (range, 18-29 months) after transplantation. Two of the eight patients with resistant disease (25%) are disease-free at 20 and 28 months. There was one procedure-related death from haemorrhage and four disease-related deaths at six, seven, eight and 13 months after transplantation. CONCLUSION: Autologous bone marrow transplantation may provide an effective salvage therapy in advanced Hodgkin's disease, particularly for patients with treatment-sensitive disease and a low tumour burden.

Adult

[Cochlear implantation].

Since the Israeli cochlear implant program was started in June 1989, 74 candidates have been evaluated for implantation. The main causes for hearing loss were meningitis (16 patients), aminoglycoside toxicity (9), congenital (6), viral (e.g. mumps) (6), and middle ear infection. Candidates were rejected mainly due to psychosocial factors (40%) and audiological parameters (30%). 16 postlingual deaf were implanted. In 7 of them (43.7%) the results were excellent, in 4 (25.0%) good, in 3 (18.7%) fair; 1 case is currently in a training program and 1 is a failure. There were 2 major complications: facial nerve palsy which necessitated surgical decompression, and insertion of the electrodes into the hypotympanic air cells, corrected by reoperation.

Cochlear Implants

[Primary hypothyroidism in normal thyroid gland morphology].

A 25 year old patient developed hypothyroidism with antibodies against thyroglobulin, thyroid microsomes and thyrotropin receptors. Thyroid 99m-technetium-uptake was 0%. Ultrasound investigation revealed a normal sized, homogenous thyroid gland. Histology showed lymphocyte infiltration but regular follicles. These results suggest the cause of hypothyroidism to be thyrotropin inhibiting immunoglobulins with no parenchyma-destroying properties.

Adult

[Severe respiratory syncytial virus pneumonia following bone marrow autograft. 3 cases].

Three patients developed severe respiratory syncytial virus pneumonia after bone marrow autograft for acute leukaemia. Clinically, the disease presents as interstitial or bilateral alveolo-interstitial pneumonia with hypoxaemia. Signs of ENT infection (otitis media, sinusitis) are present in 30 percent of the cases. In all 3 patients, the syncytial virus was isolated by direct immunofluorescence in bronchoalveolar lavage fluid. In 2 patients the infection began soon after the autograft, in deeply aplastic subjects, and required intubation and assisted ventilation. These 2 patients died despite inhalation of aerosolized ribavirin combined, in one of them, with ribavirin injections. In the third patient the infection began some time after the autograft and responded well to ribavirin in aerosols. In these three cases the viral infection occurred in an epidemic and nosocomial context. The respiratory syncytial virus is usually transmitted by the hands. Owing to the severity of this infection with lung involvement in immunodepressed patients, specific prophylactic measures should be taken side by side with the conventional measures.

Administration, Inhalation

[A lethal course in pseudomembranous enterocolitis during the parenteral administration of vancomycin and imipenem].

A 48-year-old woman required mechanical ventilation after aortic valve replacement for decompensated aortic valve stenosis when bleeding complications developed and rethoracotomy had to be performed. Acute renal failure necessitated haemodialysis. Septic fever of unknown aetiology failed to respond to oxacillin, cefotaxim and tobramycin. The endotracheal cannula and central venous catheter were changed on the 24th postoperative day and the antibiotic treatment altered to 250 mg imipenem and 125 mg vancomycin three times daily intravenously. The fever soon subsided, but recurred on the 32nd postoperative day, accompanied by increasing leucocytosis. The patient was obstipated but had no intraabdominal signs. Four days later ultrasonography demonstrated thickening of the intestinal wall and coloscopy showed typical pseudomembranous colitis. Intestinal contents were positive for Clostridium difficile toxin. Despite immediate rectal and intragastric administration of 250 mg vancomycin four times daily the patient died of pseudomembranous colitis, confirmed at autopsy. The case demonstrates that vancomycin cannot always prevent the development of pseudomembranous colitis.

Colon

Phase II evaluation of piroxantrone in renal cell carcinoma. A Southwest Oncology Group Study.

The Southwest Oncology Group (SWOG) studied the response rate and toxicity of piroxantrone (150 mg/m2 q 21 days) in patients with advanced metastatic renal cell carcinoma. Among 32 eligible patients, there were no partial nor complete responses. There were two mixed responses. Significant white cell toxicity, anemia, nausea, and vomiting were observed. Mild or moderate degrees of fever, malaise, and stomatitis occurred. No significant cardiac toxicity was noted. Piroxantrone does not have significant activity as a single agent in advanced renal cell carcinoma.

Adult

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