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Biomedical subjects

J Zyroff

Publications and source records attributed to J Zyroff.

At least 19 recordsLinked to original sources
PubMed1999

Method for intracellular magnetic labeling of human mononuclear cells using approved iron contrast agents.

A method for intracellular iron labeling of human mononuclear cells (lymphocytes and monocytes) for magnetic resonance imaging (MRI) using simple incubation of cells with approved MRI iron contrast agents is presented. Labeled cells can be detected by MRI in vitro, and this suggests the possibility that the technique could become a marker for in vivo lymphocyte and monocyte trafficking studies in acute inflammatory lesions such as those in Multiple Sclerosis.

Cell Survival↗
PubMed1996

The treatment of chronic progressive multiple sclerosis with cladribine.

A 2-year, placebo-controlled, double-blind, crossover study was started in 1992 to evaluate cladribine, an immunosuppressive drug, in the treatment of chronic progressive multiple sclerosis. In the first year patients were given cladribine 0.10 mg/kg per day for 7 days as four monthly courses for a total of 2.8 mg/kg or placebo. During the second year patients treated with placebo during the first year were given i.v. infusions of 0.10 mg, 0.05 mg, and 0.05 mg of cladribine per kg of body weight per day for 7 consecutive days in three successive monthly courses, for a total dose of 1.4 mg/kg. Patients who had been treated previously with cladribine were crossed over to placebo. Analysis of the results revealed a favorable influence on the neurological performance scores, both in the Kurtze extended disability status and the Scripps neurological rating scale, and on MRI findings in patients treated with cladribine. In the first year the most striking finding was that while clinical deterioration continued in the placebo-treated patients, the condition of patients who received cladribine stabilized or even improved slightly. Toxicity and therapeutic response were dose-related.

Adult↗
PubMed1996

Development of cladribine treatment in multiple sclerosis.

Cladribine is a new type of drug with properties of selective lymphocyte suppression that appear to favorably alter the clinical course of progressive multiple sclerosis (MS). The history of the development of cladribine treatment in chronic progressive MS is discussed, and the application of cladribine treatment to progressive multiple sclerosis in a double-blind, placebo crossover study is reviewed. Cladribine selectively targets both resting and dividing lymphocytes and may be able to destroy the activated lymphocytes that induce CNS demyelination, thus producing stabilization or improvement in chronic MS. Although the role of cladribine has not yet been fully defined, additional studies are underway to evaluate the efficacy and safety of cladribine in both progressive MS and relapsing-remitting MS.

Cladribine↗
PubMed1994

Cladribine in treatment of chronic progressive multiple sclerosis.

Chronic progressive multiple sclerosis (MS) is a severely disabling demyelinating disease in which autoimmune processes seem to have a major role. The nucleoside drug cladribine is a potent lympholytic agent with few side-effects. We have studied its efficacy and safety in a randomised double-blind trial. 51 patients (48 entered as matched pairs) received four monthly courses of 0.7 mg/kg cladribine or placebo (saline) given through a surgically implanted central line. Neurologists with no knowledge of which medication the patient was receiving examined the patients monthly and noted two rating scale scores (Kurtzke and Scripps). Cerebrospinal fluid and brain magnetic resonance imaging (MRI) examinations were done at 6 and 12 months. Average neurological scores, demyelinated volumes on MRI, and concentrations of oligoclonal bands in cerebrospinal fluid were stable or improved in the patients receiving cladrabine but continued to deteriorate in patients on placebo. Mean paired (placebo minus matched cladribine) differences at 12 months relative to baseline were 1.0 (SE 0.4) for the Kurtzke scores, -13.9 (2.3) for the Scripps scores, 4.57 (1.17) mL for demyelinated volumes, and 7.3 (3.3) arbitrary units for concentrations of oligoclonal bands. Cladribine was generally well tolerated and clinically significant toxicity occurred in only 1 patient, in whom severe marrow suppression developed with complete recovery after several months. 1 patient died of newly acquired hepatitis B, an event unlikely to be related to cladribine. We conclude that the immunosuppressive drug cladribine influences favourably the course of chronic progressive MS.

Adult↗
PubMed1993

2-Chlorodeoxyadenosine dose escalation in nonhematologic malignancies.

PURPOSE: We performed a dose-escalation study of 2-chlorodeoxyadenosine (2-CdA) in solid tumors to determine the maximum-tolerated dose (MTD) and define its toxicity profile at higher doses. PATIENTS AND METHODS: Twenty-one patients, seven with malignant astrocytoma, twelve with metastatic melanoma, and two with metastatic hypernephroma, were enrolled onto the study. Patients were entered onto cohorts that received 0.10, 0.15, or 0.20 mg/kg/d of 2-CdA by continuous intravenous infusion for 7 days every 28 days. 2-CdA levels were determined by radioimmunoassay. In tumor tissue samples, deoxycytidine kinase (dCK) levels were measured by both enzyme activity and immunoreactive protein analysis. RESULTS: Of seven patients treated with 2-CdA at 0.1 mg/kg/d, one experienced grade 3 or 4 myelotoxicity. Of 11 patients treated at 0.15 mg/kg/d, four experienced myelotoxicity, two after a single course of 2-CdA. All three patients who received 2-CdA at 0.2 mg/kg/d experienced myelosuppression. Neurologic events occurred in two patients, both with malignant melanoma. Two of seven patients (28.6%) with astrocytomas obtained partial responses with a median duration of 8 months. 2-CdA penetrated the blood-brain barrier. An association was found between dCK levels as measured by enzymatic activity and immunoreactive proteins, but this did not correlate with 2-CdA tumor responsiveness. CONCLUSION: The MTD for 2-CdA delivered as a 7-day intravenous infusion in patients with nonhematologic malignancies was determined to be 0.1 mg/kg/d, the same as the MTD for patients with hematologic malignancies. There was no clinical correlation with dCK expression and response to 2-CdA. The responses noted in patients with malignant astrocytoma warrant further phase II study.

Adult↗
PubMed1990

Spinal cord pial metastases: MR imaging with gadopentetate dimeglumine.

The purpose of this investigation was to describe gadopentetate-dimeglumine-enhanced MR findings in metastatic disease to the pial lining of the spinal cord. Correlation was made with clinical data, other radiologic studies, and pathologic findings. Eighty-six patients with a known malignancy and unexplained neurologic signs or symptoms were studied with pre- and postcontrast T1-weighted images. In seven of these patients, abnormal enhancement of the pial lining of the cord was seen on the sagittal postcontrast T1-weighted images. This appeared as a thin rim of enhancement along the surface of the cord in six patients and as a focal, thick rim of enhancement in addition to the thin rim of enhancement in the seventh patient. Axial images confirmed the location along the pial lining in each case. Precontrast T1-weighted images in all seven cases and precontrast T2-weighted images in five cases failed to detect any focal abnormalities of the pial lining of the cord. Pathologic confirmation was available in five of the seven patients. Primary malignancies in these patients included breast carcinomas (two), lymphoma (one), leukemia (one), adenocarcinoma of the lung (one), prostate carcinoma (one), and malignant melanoma (one). Three of seven patients had metastatic disease evident only within the CNS, while four patients had widespread disease outside the CNS. We conclude that contrast-enhanced MR imaging is useful in the diagnosis of pial spread of metastatic disease in patients with a known primary malignancy and unexplained neurologic signs or symptoms.

Adult↗
PubMed1989

Adverse reactions to iopamidol and iohexol myelography with special attention to headache: role of myelographic technique.

In order to identify those myelographic risk factors associated with a higher incidence of adverse effects, myelographic technique, patient variables and post-myelographic symptoms were prospectively recorded in a group of 152 patients studied with iopamidol and in a second group of 28 patients studied with iohexol. None of the technical factors studied were identified to have a statistically significant relationship with the incidence of adverse reactions. Older patients fared better than younger patients in both groups. Overall, there was a lower incidence of side effects in the iopamidol group (29%) than in the iohexol group (50%). Headache, nausea, and vomiting were the most frequent reactions seen.

Aged↗
PubMed1988

Local intra-arterial fibrinolytic therapy in acute carotid territory stroke. A pilot study.

The possibility that intra-arterial local infusion of fibrinolytic agents may achieve recanalization of previously occluded carotid territory arteries in acute stroke was tested in a prospective angiography-based open pilot study at two centers. Fifteen of 20 patients with acute symptoms (mean treatment-onset interval 7.6 hours) demonstrated complete recanalization; 10 of the 15 patients exhibited clinical improvement of varying degree by the time of hospital discharge. Four of the 20 patients suffered hemorrhagic transformation of the infarcted territory without clinical deterioration or demise. Because of the study format and the limited number of patients, dose responses for recanalization and risk relations were not established. We conclude that local intra-arterial fibrinolytic therapy may lead to cerebral arterial recanalization in acute carotid territory thrombotic stroke. The particular implications and limitations of this approach are discussed.

Acute Disease↗
PubMed1985

Duplex scanning with continuous wave Doppler for carotid disease.

Duplex scanning with the use of continuous wave Doppler instrumentation was used for the evaluation of carotid disease and compared to angiography. In twenty such patients 100% accuracy for diagnosis of total occlusion by Duplex scanning with continuous wave Doppler, was obtained. The sensitivity for those patients with 50%-99% stenosis was 92% and for those patients with 20%-49% stenosis was 75%. The overall accuracy for this diagnostic test for all groups of stenosis was 85%. This compares favorably with other noninvasive vascular techniques and is felt to be an accurate and useful technique for the detection of carotid stenosis. Several advantages of this technique are pointed out.

Angiography↗
PubMed1985

The contribution of spectral analysis to the diagnosis of carotid artery disease.

Pulsed and continuous-wave Doppler examinations with spectral analysis were performed on 258 carotid arteries in 220 patients and compared with multiplane contrast angiography. Each artery was examined for stenosis and assigned to one of four groups: normal to 19%, 20% to 49%, 50% to 99%, and occlusion. The incidence of disease was 70%. Diagnostic sensitivity with all noninvasive techniques varied from 76% to 90% depending on the degree of stenosis, with an overall accuracy rate of 86%. In an attempt to evaluate the diagnostic contribution of spectral analysis, stenosis classification by peak frequency alone was compared with that of the full laboratory profile, including spectral analysis. In the 147 carotid arteries in which such data were available, diagnostic sensitivity was improved with spectral analysis by 8% to 29% depending on the degree of stenosis. Detection of occlusions was unchanged. The major contribution of spectral analysis was in detecting non-flow-limiting stenoses of 20% to 49%. Spectral analysis added little to the diagnostic ability of peak frequency to detect lesions with greater than 50% stenosis. Spectral analysis of either pulsed Doppler or continuous-wave Doppler signals is an accurate noninvasive method for evaluating carotid bifurcation disease, which particularly improves the detection of non-flow-limiting stenoses.

Arterial Occlusive Diseases↗
PubMed1984

Recurrent carotid artery stenosis following endarterectomy.

Spectral analysis was used to examine 257 carotid arteries in 227 patients who had undergone carotid endarterectomy at 1, 3, 6, and 12 months after surgery and annually thereafter. Routine intraoperative completion angiography ensured that the operations were technically satisfactory. Postoperative restenoses were identified in 38 patients (15%). In 23 arteries (9%), the restenosis exceeded a 50% diameter reduction while in 15 arteries (6%) the stenosis was less than 50% of the diameter. Restenosis developed in 24/96 women (25%) and 14/161 men (9%). Twenty-nine (70%) stenotic lesions occurred within 12 months. In three patients early lesions regressed. Reoperation with patch angio-plasty was required in six patients. When the 219 carotid arteries that remained widely patent were compared to the 38 that restenosed , no differences were noted for age, diabetes mellitus, hypertension, smoking, or degree of preoperative stenosis. Early stenotic lesions appear to be due to myointimal hyperplasia, which is probably platelet mediated. The predominant female sex distribution may be explained by differences in platelet responsiveness in men and women.

Arterial Occlusive Diseases↗
PubMed1981

Raeder syndrome associated with lesions of the internal carotid artery.

The authors describe 3 patients with Raeder syndrome who also had lesions of the internal carotid artery in the region of the ascending sympathetic chain. One patient apparently had weakening of the artery wall, caused by extension of inflammatory disease, with hemorrhage brought on by exertion; another patient had a psuedoaneurysm possibly related to biopsy or irradiation, while a third had an aneurysm which may have been caused by a carotid artery dissection at the time of a whiplash injury many years earlier.

Adult↗
PubMed1981

Primary intracranial hypotension and bilateral isodense subdural hematomas.

A 39-year-old woman with headache and an organic mental syndrome was found to have primary intracranial hypotension (PIH). Bilateral isodense subdural hematomas were discovered in association with an absence of detectable CSF pressure on two lumbar punctures. This case study emphasizes that PIH is not an entirely benign condition and that intracranial hemorrhage may accompany persistent intracranial hypotension.

Adult↗
PubMed1970

Synergism between cysteine and alkylating agents.

Contrary to expectation, l-cysteine did not protect Escherichia coli from the lethal action of two monofunctional alkylating agents (nitrosomethylurethane and methylmethane sulfonate). The antibacterial action of these compounds was actually greatly enhanced by l-cysteine. This synergistic effect was also exhibited, to some extent, by d-cysteine but not by homocysteine, S-methylcysteine, or serine. The synergistic action between methylating agents and l-cysteine was not due to the formation of S-methylcysteine. l-Cysteine had no effect on the bacteriostatic action of ethylmethane sulfonate.

Alkanes↗
PubMedDate not supplied

A double-blind, placebo-controlled, randomized trial of cladribine in relapsing-remitting multiple sclerosis.

We conducted an 18-month, placebo-controlled, double-blind study to evaluate cladribine in the treatment of 52 patients with relapsing-remitting multiple sclerosis. Patients received either placebo or cladribine 0.07 mg/kg/day by subcutaneous injection for 5 consecutive days as six monthly courses for a total cumulative dose of 2.1 mg/kg. Analysis of results revealed a statistically significant favorable effect of cladribine on the joint frequency and severity of relapses and magnetic resonance imaging (MRI) findings. MRI-enhancing lesions were completely suppressed in the cladribine patients by the sixth month of treatment. Mild segmental herpes zoster occurred in two cladribine-treated patients and one patient receiving placebo. Otherwise, there were no side effects or adverse events. We conclude that cladribine shows promise as a treatment for relapsing-remitting multiple sclerosis.

Administration, Cutaneous↗