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Biomedical subjects

J Tobias

Publications and source records attributed to J Tobias.

At least 37 records · Page 2Linked to original sources
PubMed1990

Neoadjuvant bleomycin, ifosfamide and cisplatin in cervical cancer.

Patients with advanced and bulky early-stage cancer of the cervix have an unfavourable prognosis, which may be improved by initial neoadjuvant, cytoreductive chemotherapy. In a phase II study, coordinated at the West Midlands CRC Clinical Trials Unit, Birmingham, using ifosfamide (IFX) in combination with cisplatin and bleomycin (BIP) in advanced and recurrent cervical cancer, we demonstrated a response rate of 69%. This regimen produces rapid responses with acceptable toxicity and has potential for use as neoadjuvant therapy prior to radical radiotherapy in patients presenting with advanced and bulky early-stage disease. In an initial pilot study of this approach, 13 of 19 patients (68%) with primary inoperable disease showed significant tumour regression prior to radical local radiotherapy. Interim analysis of the first 66 patients entered into a randomized study evaluating the value of this approach has shown complete clinical tumour resolution after radical radiotherapy in 24/32 patients (75%) treated with up to three cycles of BIP prior to radiotherapy vs 19/34 patients (56%) treated with radiotherapy alone. There was no evidence that neoadjuvant chemotherapy enhances the acute toxic effects of pelvic radiotherapy. This approach has the potential for improving the outlook in patients with poor-prognosis primary disease.

Adult↗
PubMed1989

Glucocorticoids impair bone resorptive activity and viability of osteoclasts disaggregated from neonatal rat long bones.

It is generally believed that glucocorticoids cause osteoporosis through a combination of decreased bone formation and increased bone resorption. However, the direct effect of glucocorticoids on osteoclasts has not been determined. We therefore tested the effects of hydrocortisone and dexamethasone on bone resorption by osteoclasts disaggregated from neonatal rat long bones. Hydrocortisone and dexamethasone caused a dose-dependent inhibition of osteoclastic bone resorption in the range 10(-7) to 10(-5) M, and 10(-9) to 10(-6) M, respectively, at concentrations likely to occur during therapy and disease. Inhibition of bone resorption was found to be associated with impaired osteoclast survival: osteoclast numbers were reduced to approximately 25% of control values by 10(-6) M hydrocortisone and 10(-7) M dexamethasone. Osteoclast cytotoxicity by glucocorticoids was completely antagonized by progesterone, which itself had no effect on osteoclast survival. Analysis of the time course of these inhibitory effects showed a nonsignificant reduction in survival by 6 h and marked inhibition of survival by 12 h. We could detect no specific changes in osteoclast morphology in association with this impaired viability. The relative potencies of the glucocorticoids for impairment of osteoclast viability was similar to their relative affinities for binding the glucocorticoid receptor, and this, together with inhibition by progesterone, suggests a receptor-mediated mechanism. Such a receptor-mediated cytotoxic action of glucocorticoids has only previously been reported with lymphoid cells. The sensitivity of osteoclasts to the lethal effects of glucocorticoids suggests that glucocorticoids may have a role in physiology as inhibitors of osteoclastic bone resorption.

Animals↗
PubMed1989

The role of ifosfamide in cervical cancer.

A series of phase II studies using ifosfamide as a single agent and in combination with cisplatin and bleomycin (BIP) in advanced and recurrent cervical cancer were coordinated at the West Midlands Cancer Research Campaign Clinical Trials Unit, Birmingham, UK. The aim of these studies was to identify single agents and combination regimens that might be of value for palliation and have potential for neoadjuvant and adjuvant therapy in primary treatment. Ninety-eight patients were studied. Seventy-nine patients with disease not amenable to radical local therapy were treated with single-agent ifosfamide or the BIP combination. In 30 patients treated with single-agent ifosfamide, ten objective responses (33%) were seen, with one complete response. In 49 patients treated with BIP, 34 objective responses (69%) were seen, with ten complete responses (20%). Eleven (79%) of 14 patients with primary inoperable disease had at least a 50% reduction in tumor bulk before radical local radiotherapy. Toxicity resulted in alopecia, nausea and vomiting, myelosuppression, infection, reduction in renal function, and disturbance of consciousness. There was no evidence that neoadjuvant chemotherapy enhanced the acute toxic effects of pelvic radiotherapy. These data indicate that ifosfamide is highly active in cervical cancer and that in combination with bleomycin and cisplatin, it can be used for effective palliation and cytoreduction in around 70% of patients. Ifosfamide-containing regimens have potential for use as neoadjuvant and adjuvant therapy in patients at high risk of recurrence with conventional treatment. These hypotheses are currently being tested in prospective randomized trials.

Adult↗
PubMed1989

Giant-cell neoplasm of the sphenoid sinus.

A rapidly growing giant-cell neoplasm arising in the sphenoid sinus of a 26-year-old man is reported. The patient's only initial symptoms were severe headaches and left sixth-nerve palsy. Computerized tomography of the brain showed extensive tumor infiltration of the bony structures and soft tissues of the base of the skull. A transsphenoidal surgical procedure proved unsuccessful in removing the tumor. Histologic examination revealed a proliferation of osteoclast-type giant cells against a background of highly atypical mononuclear cells, raising the question of malignancy. The differential diagnosis and problems in nomenclature of this lesion are discussed.

Adult↗
PubMed1985

Sensitivity of MRI in metastatic neoplasia: a case report.

Serial magnetic resonance imaging (MRI) and computed tomography (CT) were performed on a patient with metastatic lung cancer to brain. Magnetic resonance (MR) visualized two foci of intracerebral metastasis six weeks prior to CT.

Adenocarcinoma↗
PubMed1985

Carotid artery and aortic arch imaging with ECG gating in DSA.

New computer software for gated digital subtraction angiography imaging was used to study 57 patients over 3 months. Better mask registration on isolated sets of systolic and diastolic images improved image quality. Detail of vessel outline and lesion was better than that seen on non-gated images.

Aorta, Thoracic↗
PubMed1985

MR imaging of multiple sclerosis: comparison with clinical and CT examinations in 74 patients.

Magnetic resonance (MR) imaging, the latest test for evaluation of patients with multiple sclerosis (MS), was assessed against clinical evidence in 74 patients with definite or probable MS. MR imaging was positive in 55 (85%) of 65 patients with definite MS but in only one (11%) of nine patients with probable MS. The examination is most likely to be positive when the patient is classified clinically as having definite MS; when the disease is active and not in remission; and if the constellation of symptoms indicates a multiplicity of regions with neurologic dysfunction. The examination was most sensitive for detecting lesions in the cerebral hemispheres, the posterior fossa, and the cervical spinal cord, in that order; it did not detect any lesions in the optic nerves. The paraclinical tests and MR imaging were of equal sensitivity in detecting MS lesions, but the latter method was more specific in localization. Cerebrospinal fluid evaluation was slightly less sensitive than the other two tests. There was no correlation between MR imaging and these examinations. The authors conclude that MR imaging is more sensitive than computed tomography (CT), which was positive in 25% of 59 patients with definite MS; it is always positive when CT is positive; and it probably can replace CT in the diagnosis and follow-up of patients with MS.

Adult↗
PubMed1984

Instant oxygen delivery system for manual resuscitators.

To help prevent the use of manual resuscitators without supplemental oxygen we developed a device that automatically starts the flow of oxygen when the resuscitators is put into use and then stops the oxygen flow when the resuscitator is returned to its assigned resting place. This instant oxygen delivery valve does not compromise oxygen flowrates from the gas source. We have used this device without problems for several months in our intensive care until.

Hospital Bed Capacity, 500 and over↗
PubMed1982

High-dose cyclophosphamide with autologous marrow transplantation as initial treatment of small cell carcinoma of the bronchus.

Sixteen patients with untreated small cell carcinoma of the bronchus received cyclophosphamide in a total dose of 160-200 mg/kg. Autologous marrow transplantation was used to minimise the period of hypoplasia and 2-mercaptoethane sulphonate to prevent urothelial toxicity. The procedure was well tolerated, with predictable and manageable toxicity. Complete radiological and bronchoscopic response was achieved in seven patients and partial response in a further seven. High-dose cyclophosphamide may be a useful initial treatment for this disease.

Adult↗
PubMed1978

Evidence for lack of phosphatidic acid and phospholipase D activity in milk.

Phosphatidic acid could not be demonstrated when milk was assayed for phospholipase D activity even when lecithin was added. The concentration of "free" choline in milk remained the same before and after addition of lecithin. However, phosphatidic acid and an increased concentration of "free" choline were demonstrated when cabbage phospholipase D was added to raw milk. The concentration of phosphatidic acid and "free" choline in milk increased appreciably when both lecithin and cabbage phospholipase D were added to raw milk. Phospholipase D activity in milk was assayed at 23.5 C, pH 5.6, in the presence of 10% vol/vol of diethyl ether and .015M calcium chloride. "Free" choline was determined by adjusting the acid whey from milk to pH 11 and adding a freshly prepared 3% methanolic solution of ammonium reineckate. The precipitated choline reineckate was washed, dissolved in acetone, and its absorbance measured at 520 nm. The absence or presence of phosphatidic acid was shown by thin-layer chromatography. These results refute a previous report which proposed that both phosphatidic acid and phospholipase D were in milk.

Animals↗