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Biomedical subjects

N Russell

Publications and source records attributed to N Russell.

At least 55 records · Page 3Linked to original sources
PubMed1993

Feasibility study of intraarterial vs intravenous cisplatin, BCNU, and teniposide combined with systemic cisplatin, teniposide, cytosine arabinoside, glycerol and mannitol in the treatment of primary and metastatic brain tumors.

Sixteen patients with intracerebral tumors received intraarterial cisplatin, teniposide, and BCNU combined with intravenous cisplatin, teniposide, and cytosine arabinoside. Oral glycerol and intravenous mannitol were given along with the intravenous chemotherapy in an attempt to increase drug delivery to tumor by augmenting tumor blood flow. Thirteen additional patients were treated with the same regimen, but received all the chemotherapy intravenously. Of the 16 patients receiving intraarterial chemotherapy (median survival, 14 weeks), none responded, 5 (31%) were stable for > 8 weeks, 8 (50%) failed, and 3 (19%) were unevaluable due to early death. Of the 13 patients receiving all their treatment intravenously (median survival, 13 weeks), 3 (23%) responded, 1 (8%) was stable, 7 (54%) failed, and 2 (15%) were unevaluable due to early death. In the patients receiving intraarterial chemotherapy, toxicity included ipsilateral retinal toxicity (2 patients), ocular pain or headache (10), periorbital swelling and flushing (6), increased brain edema with focal neurological deficits and drowsiness (5), and catheter-related carotid artery thrombosis followed by fatal herniation (1). Myelosuppression was worse in patients who received all their treatment intravenously than in those receiving intraarterial chemotherapy (p < 0.05). Neutropenic sepsis developed in 4 patients on the intraarterial arm (1 fatal) and in 5 patients on the intravenous arm (2 fatal). Other toxic effects were similar whether or not patients received intraarterial treatment or only intravenous treatment. Overall, toxicity of this regimen was excessive, and response rates were lower than would have been expected with single agent therapy.

Adult↗
PubMed1993

Expression of different conformations of p53 in the blast cells of acute myeloblastic leukaemia is related to in vitro growth characteristics.

Expression of the wild-type p53 gene has an important role in cell differentiation, maturation and apoptosis. Mutation of the p53 gene is associated with tumour development and mutant p53 can promote cell proliferation. Recently wild-type p53 has been demonstrated to exist in two conformational variants: one acting as a suppressor (PAb240-/PAb1620+) and one as a promoter (PAb240+/PAb1620-) of cell proliferation. We have analysed the expression of p53 by flow cytometry in blast cells from 34 patients with acute myeloblastic leukaemia in relationship to the proliferation characteristics of these cells in a clonogenic assay. Blasts from three out of 34 patients did not express p53 using the antibodies: PAb421, PAb1801, PAb240 and PAb1620. The remaining 31 samples expressed p53 detected by PAb240 which recognises mutant p53 and is predicted to recognise wild-type p53 in the promoter conformation. Blasts from 19 out of 31 cells which expressed PAb240 co-expressed PAb1620, expression of PAb1620 was associated with non-autonomous growth in vitro. In contrast, the majority of blasts with the p53 phenotype of PAb240+/PAb1620- or which lacked p53 expression exhibited autonomous growth characteristics in vitro. Furthermore expression of PAb1620 in blasts with autonomous growth cells could be detected following growth inhibition using monoclonal antibodies against autocrine growth factors. Our data demonstrate that in AML cells, p53 conformation is related to the growth characteristics of the cells and is regulated by either exogenous or autocrine haematopoietic growth factors.

Animals↗
PubMed1992

Neurobrucellosis: clinical and therapeutic features.

Eighteen patients with neurobrucellosis are described. Eleven patients had meningitis alone or with papilledema, optic neuropathy, or radiculopathy. Four patients had meningovascular complications manifested by stroke or intracerebral hemorrhage from a presumed mycotic aneurysm. Two patients had parenchymatous dysfunction, including a child who had a cerebellar syndrome without evidence of direct infection of the central nervous system. One patient presented with polyradiculopathy. Twelve of 16 patients had pleocytosis; none had cell counts greater than 419 x 10(6)/L. Most patients had hypoglycorrhachia and elevated levels of protein in the cerebrospinal fluid (CSF). Results of an agglutination test for Brucella in serum were positive for all patients. Six of 16 patients had positive blood cultures, and four of 14 had positive CSF cultures. Antimicrobial treatment included concurrent administration of two or more of the following drugs: streptomycin, tetracycline (or doxycycline), rifampin, and trimethoprim-sulfamethoxazole. Eleven patients fully recovered. Five patients were left with residual neurological deficits. Four of these patients suffered permanent hearing loss, one of whom also had significant loss of vision in one eye. One elderly senile patient with meningovascular brucellosis remained in a vegetative state despite receiving antimicrobial therapy for 6 months. One patient died due to rupture of a mycotic aneurysm within 7 days of initiation of therapy. One other patient was treated after sustaining an intracerebral hemorrhage, but this patient's condition was diagnosed only after discharge.

Adolescent↗
PubMed1992

Interleukin 1 has positive and negative regulatory effects in human long-term bone marrow culture.

The observations that interleukin 1 (IL-1) increases the production of colony-stimulating factors (CSFs) by stromal cells and acts in synergy with those CSFs to stimulate the growth of progenitor cells suggest that IL-1 may have an important role in stimulating hemopoiesis. However, IL-1 also induces the synthesis by stromal cells of inhibitors of hemopoiesis including tumor necrosis factor (TNF) and prostaglandin E2. We have used long-term bone marrow culture (LTBMC) to study the effect of IL-1 on hemopoiesis in the presence of a stromal cell layer. The addition of recombinant (r)IL-1 (10 U/ml) at the initiation of the LTBMC and at each weekly feed resulted in a significant stimulation of nonadherent granulocyte-macrophage colony-forming units (CFU-GM) by week 1 and a sustained increase in colony-stimulating activity (CSA) in culture supernatants. The increased CSA activity was mainly due to granulocyte colony-stimulating factor (G-CSF) as studied by the effects of neutralizing antibodies. Following this initial stimulation, however, nonadherent layer CFU-GM became significantly suppressed by week 4, and the number of nonadherent cells was also reduced. This delayed suppression of hemopoiesis induced by continuous exposure to rIL-1 was partially abrogated by the addition of indomethacin (10(-6) M) to the cultures, but anti-TNF had no such effect and we could not detect significant TNF levels either in culture supernatants or in stromal cell extracts. Our data suggest that prostaglandin inhibitors suppress the negative feedback control of myelopoiesis induced by IL-1 and therefore may have a role in augmenting IL-1 stimulation of myelopoiesis.

Bone Marrow↗
PubMed1991

Perspectives in multiple myeloma: survival, prognostic factors and disease complications in a single centre between 1975 and 1988.

One hundred and forty-one patients with multiple myeloma, diagnosed at the City Hospital, Nottingham between January 1975 and October 1986, were followed until death or for at least two years in a retrospective study. Overall median survival was 25 months, with no significant improvement occurring during the study period; increasing age, ESR and serum creatinine concentration at diagnosis were independent predictors of shortened survival. Renal impairment developed in 56 per cent of patients but only 7 per cent died of renal failure. At least one episode of infection occurred in 55 per cent of patients, most commonly in the first month. There was a significant rise in the overall incidence of infection and in the proportion caused by Gram-negative bacteria during the study period. Raised serum urea and low haemoglobin concentrations at diagnosis were independent risk factors for subsequent infection. Infection was associated with 2.75-fold increased risk of death, independent of other risk factors. Prevention of infection is an important aim for improvements in the survival of patients in multiple myeloma.

Adult↗
PubMed1990

Atypical subependymoma of the spinal cord: ultrastructural and immunohistochemical studies.

A 76-year-old woman with a 2-year history of progressive weakness of the left arm and leg underwent a laminectomy for an intradural, extramedullary, pedunculated subependymoma involving the meninges and spinal nerve roots at C7-T1. Eight months later, another operation was necessary for an intramedullary neoplasm at C3-T4. This latter tumor consisted of small, poorly developed cells, large atypical astrocytes, and ependymal cells. Neither ependymal rosettes nor papillary formations were present. Ultrastructural studies showed some features of ependymal differentiation of the large "astrocytic" cells. This case illustrates an unusual pattern of extramedullary and intramedullary presentations of subependymoma and a spectrum of cellular differentiation of neoplastic subependymal glia.

Aged↗
PubMed1990

Endogenous interleukin-1 can regulate the autonomous growth of the blast cells of acute myeloblastic leukemia by inducing autocrine secretion of GM-CSF.

We have studied peripheral blood blast cells from a patient with acute myeloblastic leukemia (AML) whose cells proliferated autonomously at high cell density, but only in the presence of adherent cells. At low cell density in suspension culture and in a clonogenic assay, blast cell growth was stimulated by recombinant granulocyte macrophage colony stimulating factor (GM-CSF) and recombinant interleukin-1 (IL-1) independently. The response to rIL-1 was inhibited (less than 90%) by anti-GM-CSF, suggesting that the proliferative response to IL-1 was mediated by GM-CSF. This was supported by experiments which demonstrated that blast cell conditioned medium prepared in the presence of IL-1 contained GM-CSF activity which stimulated the growth of normal granulocyte-macrophage precursors (CFU-GM) and of homologous GM-CSF responsive AML blasts. As IL-1 but no GM-CSF activity was detected in BCCM prepared without exogenous IL-1 and a neutralizing antibody to IL-1 inhibited the autonomous growth of blasts in suspension culture, we conclude that the endogenous secretion of IL-1 by leukemic cells stimulated autocrine GM-CSF secretion, inducing autonomous growth of the blast cell population.

Cell Division↗
PubMed1989

Intraparenchymal epithelial (enterogenous) cyst of the medulla oblongata.

Intraparenchymal solitary cyst of the medulla oblongata was diagnosed on MRI examination in a 66-year-old woman with a nine year history of progressive brainstem dysfunction and three negative CT scan examinations. Craniotomy and drainage of the cyst to the IVth ventricle led to remarkable clinical recovery. Biopsy of the wall of the cyst revealed an epithelial lining with tonofilaments, desmosomes and surface coating on ultrastructural examination. Immunohistochemistry demonstrated positive reactions of epithelium for keratins, cytokeratins, epithelial membrane antigen and Ulex Europeus lectin, indicating endodermal origin of the cyst.

Aged↗
PubMed1988

Smoking--a major cause of polycythaemia.

The importance of smoking in the aetiology of polycythaemia has been assessed in a group of patients referred to a general haematology clinic. All patients with true and relative polycythaemia (excluding those with polycythaemia rubra vera) were studied. Of the 21 such patients evaluated, 14 were smokers and had raised carboxyhaemoglobin levels and had no other demonstrable cause for their polycythaemia. The commonest physiological abnormality in these patients was a raised red cell mass combined with a low plasma volume. Six of the 14 patients were able to reduce their smoking with subsequent improvement in their haematocrits. These results suggest that smoking is a major cause of polycythaemia in an unselected series of referrals to a general haematology clinic. The early identification of these patients may be useful in planning therapy.

Carboxyhemoglobin↗
PubMed1988

Cellular blue nevus ("melanocytoma") of the spinal meninges: electron microscopic and immunohistochemical features.

A primary cellular blue nevus (melanocytoma) of the spinal canal in a 21-year-old woman is reported. Light microscopic examination revealed a melanotic neoplasm with histological patterns resembling schwannoma, dermal nevi, and neuroblastic-like tumor. The ultrastructural features of the neoplastic cells were similar to those in dermal blue nevi and melanomas. There was no evidence of arachnoidal cell differentiation. Immunohistochemistry revealed positive reactions for S-100 protein and neuron-specific enolase in many cells and no reactions for glial fibrillary acidic protein, cytokeratins, epithelial membrane antigen, 70-kD neurofilament protein, or Leu-7. Vimentin was strongly positive in the melanocytic cells as well as in the arachnoidal cells of involved meninges. The ultrastructural and immunohistochemical features support the nevoid nature of this tumor, which is frequently mislabeled as "melanotic meningioma."

Adult↗
PubMed1987

Combined intraommaya methotrexate, cytosine arabinoside, hydrocortisone and thio-TEPA for meningeal involvement by malignancies.

Twenty-three adult patients with meningeal involvement by a variety of malignancies were treated with the intra-Ommaya combination of methotrexate, hydrocortisone, cytosine arabinoside, and thio-TEPA. Whole brain irradiation was also administered to most patients who had not previously received it. Most patients demonstrated improvement of cerebrospinal fluid parameters, but only 50% of the patients experienced neurological improvement. Patients who did not receive cranial irradiation and performance status 4 patients were less likely to respond than were patients who did receive cranial irradiation as part of their treatment and patients who were performance status 0-3. Four patients developed possible and 2 patients developed probable or definite serious neurological complications. Another 4 patients developed less severe, reversible neurological toxicity. It is possible (but still uncertain) that this regimen is more toxic than other less intensive regimens, and further studies should be undertaken cautiously.

Adult↗
PubMed1987

Combined intraarterial and systemic chemotherapy for intracerebral tumors.

Twenty-six patients with intracerebral tumors (predominantly gliomas) were treated with intraarterial BCNU, VM-26, and cisplatin combined with the systemic administration of VM-26, methotrexate, vincristine, bleomycin, and procarbazine. Oral glycerol was given before i.v. VM-26. Twelve patients responded (46% of all patients and 63% of the fully evaluable patients). The response rate for gliomas was 50% if all patients were considered and 71% if only fully evaluable patients were considered. The response rate did not seem to be affected by glioma grade, prior chemotherapy, or pretreatment performance status. Median time to tumor progression for responders was 19 weeks. Median survival from initiation of treatment was 21 weeks for evaluable patients and 17 weeks for all patients. Median survival from initial diagnosis was 55 weeks. Myelosuppression was dose-limiting for the systemic chemotherapy. Reversible neurological toxicity was common, but tolerable. One patient developed ipsilateral blindness, and two patients developed prolonged neurological toxicity. Pulmonary toxicity was also seen. Vertebral artery infusions proved feasible, although difficult and more toxic than carotid infusions. Overall, this regimen was not more active than the intraarterial combination of BCNU, VM-26, and cisplatin without the systemic chemotherapy. Further studies of more intensive intracarotid therapy combined with different systemic drugs are being initiated.

Adolescent↗
PubMed1987

Cytosine arabinoside plus cisplatin and other drugs as chemotherapy for gliomas.

Twenty-five evaluable patients with gliomas were treated with a combination of cytosine arabinoside plus cisplatin administered intravenously (IV). Ten of the 25 patients (40%) responded, including three of 13 patients (23%) with prior cranial radiation, and seven of 12 patients (58%) without prior cranial radiation. In a second study, intramuscular (IM) and oral caffeine were added to IV cytosine arabinoside plus cisplatin. Caffeine-induced seizures prevented escalation of the dose of caffeine to a level that would have been anticipated to potentiate the cytotoxicity of the cytosine arabinoside plus cisplatin. Twelve of 25 treated patients (48%) responded. Most of the patients had not received prior cranial radiation. In a third study, IV cytosine arabinoside was administered in combination with intracarotid and IV cisplatin, plus BCNU and tenoposide (VM-26). This study is continuing to accrue patients. Myelosuppression has been pronounced, but has generally been rapidly reversible. It is too early to comment on efficacy of this combination. Our results to date permit us to conclude that the combination of cytosine arabinoside plus cisplatin is capable of inducing regression of gliomas in some patients. We feel that further studies are warranted.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Keratinocyte growth-promoting activity from human placenta.

Extracts of term human placenta were tested for enhancement of proliferative growth of primary cultures of human keratinocytes. Saline extracts or supernatants from homogenates were dialyzed extensively, lyophilized, and tested in subcultures of keratinocytes in MCDB 153 medium with 0.1 mM Ca++ containing only defined supplements (insulin, hydrocortisone, transferrin, ethanolamine, phosphoethanolamine). Cells plated in the absence of EGF at moderately high densities (1000-3000 cells per cm2) formed colonies and grew in the presence of placental extract at 25-500 micrograms/ml. Extracts of cord serum or maternal serum were inactive, suggesting that the activity is derived from placental tissue. The activity is not EGF, since the activity in the placental extract, unlike EGF, did not promote growth at low cell density, was synergistic with EGF under some conditions, and did not produce changes in colonial morphology which occurred in the presence of EGF. Unlike keratinocyte growth-promoting activity in bovine hypothalamic extract, the activity is non-dialyzable and is destroyed at 100 degrees C. Placental extract could not replace any of the defined components of the medium and is therefore distinct from them. The presence of activity in the placenta with distinctive properties suggests that this is a previously undescribed material with growth-promoting properties for epithelium.

Cell Count↗