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Biomedical subjects

M Ross

Publications and source records attributed to M Ross.

At least 163 records · Page 9Linked to original sources
PubMed1994

Phase I study of recombinant human interleukin-1 beta (rhIL-1 beta) in patients with bone marrow failure.

The administration of recombinant human interleukin-1 beta (rhIL-1 beta) stimulates pluripotent cell growth and reduces mortality from infection in animal models. In this phase I trial, rhIL-1 beta (0.02-0.50 microgram/kg) was administered by 30-minute intravenous infusion once daily for 2 or 5 consecutive days. The dose was escalated with the subsequent cycle in the same patient if no hematologic response was observed. Nineteen patients with severe bone marrow failure received 60 courses of IL-1 beta. Diagnoses included autologous bone marrow transplant (BMT) (n = 5), allogeneic BMT (n = 7) or idiopathic aplastic anemia (n = 6) and 1 patient with chronic myeloid leukemia. Toxicities included fever (89%), chills (85%), hypertension (89%), hypotension (57%) and headache (95%). No complications were life-threatening and all either spontaneously resolved or were managed pharmacologically. In 8 of 19 patients there was an acute, transient increase in neutrophil counts. In 2 patients there was a transient increase in platelet count; however, no durable, clinically significant effects on peripheral blood counts were observed. In conclusion, administration of rhIL-1 beta in this population of patients had limited efficacy and moderate toxicity.

Adolescent↗
PubMed1994

The use of intensive clinic support to permit outpatient autologous bone marrow transplantation for breast cancer.

Recent studies have explored feasibility and cost considerations of administering high-dose chemotherapy with hematopoietic support in the outpatient setting. Between October 1991 and April 1993, we studied 110 women with primary metastatic breast cancer undergoing high-dose chemotherapy with hematopoietic support. Ninety-two patients were managed in an outpatient clinic after high-dose chemotherapy and autologous bone marrow transplantation and peripheral blood progenitor cells. The remaining 18 patients received the same high-dose treatment and hematopoietic support in the hospital and were discharged to a nearby hotel each night; these patients were the pilot group for this effort and also served as a control group. High-dose chemotherapy consisted of cyclophosphamide/cisplatin/carmustine. Chemotherapy was well tolerated, allowing 95% of 65 eligible patients enrolled since November 1992 to be discharged soon after chemotherapy for outpatient posttransplant support. Approximately 70% of these patients required either no hospital readmission or brief readmissions of 1 to 4 days. Median days of hospitalization required for historical groups of patients receiving high-dose chemotherapy plus bone marrow support as inpatient therapy, high-dose chemotherapy with colony-stimulating factor-primed peripheral blood progenitor cells and autologous bone marrow transplantation as inpatient therapy in a traditional transplant model, and outpatient management of autologous bone marrow transplantation patients were 37, 24.5, and 7 days, respectively, despite the same high-dose chemotherapy. Charges related to the transplant procedure were reduced by 50% over the last 2 to 5 years using the outpatient management approach. This procedure may be applicable to patients with other forms of cancer receiving intensive chemotherapeutic regimens. The use of outpatient management in a transplant setting is highly cost effective.

Adult↗
PubMed1994

Prevention of hemorrhagic cystitis after high-dose alkylating agent chemotherapy and autologous bone marrow support.

High-dose cyclophosphamide (CY) is associated with a high risk of hemorrhagic cystitis. The reported frequency ranges from 6.5 to 52% despite the use of hydration protocols. The current study reports a hyperhydration and continuous bladder irrigation protocol which resulted in a very low incidence of microscopic hematuria and no reported cases of visible hematuria. Patients received baseline fluids at 200 ml/m2/h during chemotherapy. Additional fluid boluses were given if urine output fell below 200 ml/h. Bladder irrigation was performed at a rate of 1 l/h during and for 24 h after high-dose CY. Three hundred three evaluable patients with solid tumors received high-dose chemotherapy with CY at a dose of 5625 mg/m2 over 3 days. Patients also received cisplatin 165 mg/m2 and carmustine 600 mg/m2. Some patients received thiotepa 300-750 mg/m2 instead of carmustine. The overall incidence of microscopic hematuria (> 15 RBCs per high power field) was 19%, with only 11% of patients experiencing more than 50 RBCs per high power field. No patient developed visible hematuria or symptomatic hematuria requiring intervention. These results using aggressive hyperhydration and high volumes of continuous bladder irrigation are among the best reported following high-dose CY chemotherapy.

Bone Marrow Transplantation↗
PubMed1993

Randomized trial of high-dose chemotherapy with autologous bone marrow support as adjuvant therapy for high-risk, multi-node-positive malignant melanoma.

BACKGROUND: Chemotherapy adjuvant to surgery in metastatic melanoma has been evaluated in only a few prospective randomized trials. In the treatment of metastatic melanoma, dacarbazine has response rates of 15%-25% and in several studies, when combined with other alkylating agents, has yielded even higher response rates. Among the highest response rates are those achieved by using high-dose chemotherapy regimens combined with autologous bone marrow support (transplantation). PURPOSE: We conducted a prospective randomized clinical trial to test the efficacy of high-dose alkylating agents in combination with autologous bone marrow support given as adjuvant therapy for high-risk stage II (World Health Organization) melanoma. METHODS: Thirty-nine patients with metastases involving five or more lymph nodes were randomly assigned to one of two treatment arms within 8 weeks of lymphadenectomy: immediate treatment or observation only. The immediate-treatment arm consisted of 19 patients who, immediately after random assignment, received high-dose chemotherapy with alkylating agents, followed 3 days later by reinfusion of autologous bone marrow. The observation arm consisted of 20 patients who were observed until relapse (confirmed by biopsy) and were then treated with the identical high-dose alkylating agent chemotherapy followed by reinfusion of autologous bone marrow. Bone marrow was harvested from the patients under general anesthesia 1-2 weeks prior to chemotherapy and was cryopreserved. Chemotherapy consisted of intravenous administration of cyclophosphamide (1875 mg/m2 as a 1-hour infusion daily for 3 days), cisplatin (55 mg/m2 per day by continuous infusion over the same 72-hour period), and carmustine (BCNU) (600 mg/m2) given immediately after cisplatin on the 4th day as a 2-hour infusion. The total doses of the three drugs were 5625, 165, and 600 mg/m2, respectively. All patients received medical evaluations every 6-12 weeks over the study period. Kaplan-Meier estimates were used to determine the time to disease progression on the basis of intent to treat. RESULTS: There was no statistically significant difference in overall survival or in time to disease progression between the two treatment arms. However, the median time to progression was 16 weeks in the observation arm and 35 weeks in the immediate-treatment arm. CONCLUSIONS: Immediate adjuvant high-dose chemotherapy with alkylating agents followed by autologous bone marrow support more than doubled the time to disease progression compared with observation alone, though the difference was not statistically significant. No differences in overall survival were noted.

Adult↗
PubMed1993

ME1 and GE1: basic helix-loop-helix transcription factors expressed at high levels in the developing nervous system and in morphogenetically active regions.

Several class A basic helix-loop-helix (bHLH) transcription factors have been cloned from the developing mouse and chick nervous system. The cloned cDNAs (ME1, ME2, ME3, ME4, in the mouse and GE1, GE2 in the chick) have HLH coding regions highly homologous to other known class A bHLH genes. The genes corresponding to ME1 and GE1 are abundantly expressed during development of the central nervous system. ME1 and GE1 are expressed in proliferating neuroblasts and in cells at the initial stages of differentiation (for example in the external granule cell layer of the cerebellum and in the lateral region of the ventricular zone in the developing neural tube and cortex). They are also expressed at high levels in morphogenetically active regions such as limb buds, somites and mesonephric tubules. The expression of ME1 and GE1 decreases once cellular differentiation is over. Based on the expression of ME1 and GE1 in regions of active cellular proliferation and differentiation and on the known role of other bHLH factors in development, we suggest that ME1 and GE1 play important roles during development of the nervous system as well as in other organ systems.

Amino Acid Sequence↗
PubMed1993

Comparative effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) on priming peripheral blood progenitor cells for use with autologous bone marrow after high-dose chemotherapy.

Two hematopoietic colony-stimulating factors, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF), have been shown to accelerate leukocyte and neutrophil recovery after high-dose chemotherapy and autologous bone marrow (BM) support. Despite their use, a prolonged period of absolute leukopenia persists during which infections and other complications of transplantation occur. We collected large numbers of peripheral blood (PB) progenitors after CSF administration using either G-CSF or GM-CSF and tested their ability to affect hematopoietic reconstitution and resource utilization in patients undergoing high-dose chemotherapy and autologous BM support. Patients with breast cancer or melanoma undergoing high-dose chemotherapy and autologous BM support were studied in sequential nonrandomized trials. After identical high-dose chemotherapy, patients received either BM alone, with no CSF; BM with either G-CSF or GM-CSF; or BM with G-CSF or GM-CSF and G-CSF or GM-CSF primed peripheral blood progenitor cells (PBPC). Hematopoietic reconstitution, as well as resource utilization, was monitored in these patients. The use of CSF-primed PBPC led to a highly significant reduction in the duration of leukopenia with a white blood cell (WBC) count under 100 and 200 cells/mL, and neutrophil count under 100 and 200 cells/mL with both GM- and G-CSF primed PB progenitor cells, compared with the use of the CSF with BM or with historical controls using BM alone. In addition, the use of CSF-primed PBPC resulted in a significant reduction in median number of antibiotics used, days in the Bone Marrow Transplant Unit, and hospital resources used. Patients receiving G-CSF primed PBPC also experienced a reduction in the median number of days in the hospital, red blood cell (RBC) transfusions, platelet transfusions, days on antibiotics, and discounted hospital charges. Phenotypic analysis of the CSF-primed PBPC indicated the presence of cells bearing antigens associated with both early and late hematopoietic progenitor cells. The use of CSF-primed PBPC can significantly improve hematopoietic recovery after high-dose chemotherapy and autologous BM support. In addition, the use of G-CSF-primed PBPC was associated with a significant reduction in hospital resource utilization, and a reduction in hospital charges.

Adult↗
PubMed1993

A practitioner's guide to HIV testing.

So far Could it be HIV? has examined many of the clues obtained from the clinical history and physical examination that might make an alert health care worker consider the diagnosis of HIV infection. Here we examine strategies for seeking permission for HIV testing and give advice on interpreting the results.

AIDS Serodiagnosis↗
PubMed1993

Comparison of the flashlamp pulsed dye laser with the argon tunable dye laser with robotized handpiece for facial telangiectasia.

This prospective study compares the efficacy, side effects, and patient acceptance of the flashlamp pulsed dye laser (FPDL) with the argon tunable dye laser with robotized handpiece (ATDL/H) for facial telangiectasias. Seventeen adult patients with bilaterally symmetric facial telangiectasias were enrolled. The right cheek on each patient was treated in one session with the FPDL at a fluence of 6.0-6.75 J/cm2 and a spot size of 5 mm. The left cheek was treated at the same session with the ATDL/H at a power of 1 W, a fluence of 26-27 J/cm2, and a hexagonal treatment area of 13 mm (127 individual 1 mm spots grouped mechanically by the handpiece). Patients were evaluated subjectively and by the investigators at 2, 4, and 6 weeks for blistering, swelling, bruising, changes in pigment, scarring, overall efficacy, and patient preference. Average treatment times were 5.4 minutes for FPDL and 9.4 minutes for ATDL/H. Blistering, crusting, and discomfort were completely resolved on both sides by week 2 in all patients. Bruising occurred in all patients with FPDL but had resolved in 62.5% of patients at 2 weeks and 100% at 4 weeks. There was no bruising with ATDL/H. Postinflammatory hyperpigmentation was much more prominent with FPDL but had resolved in 88% of cases by week 6. As rated by the investigators 100% of the FPDL treated areas showed excellent clearing of telangiectasias, compared with 47% of ATDL/H treated areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

State changes in brain activity shown by the uptake of 99mTc-exametazime with single photon emission tomography in major depression before and after treatment.

Twenty-eight patients with a major depressive episode previously investigated at rest using Single Photon Emission Tomography (SPET or SPECT) with 99mTc-exametazime, were followed up at an interval of 9-28 months with the same investigation after full recovery. All patients were unipolar and were rated on the Newcastle scale and with the 17-item Hamilton scale. The uptake of 99mTc-Exametazime was expressed relative to calcarine/occipital cortex. Sixteen patients were scanned when optimally matched for drug treatment (4) or on both occasions drug free (12). The other 12 patients were fully recovered but could not be matched for drug status; these patients showed significantly more retardation, diurnal mood variation and guilt at presentation. Significant bilateral increases in tracer uptake were confined to basal ganglia and inferior anterior cingulate cortex in the matched group, where there were additional increases in thalamus and posterior cingulate cortex on the right side. There were no statistically discernible changes in the neocortex in the matched sample. The unmatched sample yielded inconclusive evidence of increased tracer uptake in left temporal cortex. The findings give a potential focus to the neuropharmacological analysis of depressive illness because the topography of the state change in brain function implicates dopamine function.

Adult↗
PubMed1993

The elevation of plasma beta-endorphin levels in major depression.

Day-time plasma beta-endorphin/beta-lipotrophic hormone (beta-ENDO/beta-LPH), ACTH and cortisol have been determined in 26 patients with major depression and 25 controls. beta-ENDO/beta-LPH and cortisol were significantly elevated in patients, while ACTH was not. Cortisol levels were significantly negatively correlated with age in controls as were beta-ENDO/beta-LPH and ACTH. In patients, by contrast, cortisol levels were positively, albeit not significantly, related to age. Peptide levels were not related to age in the patient group. Instead, beta-ENDO/beta-LPH was negatively correlated with clinical ratings of symptom severity in patients and positively associated with an acute psychosocial precipitant. The findings cast further light on beta-ENDO/beta-LPH as a measure of hypothalamic-pituitary over activity in depressive illness. A negative association with symptom severity suggests that beta-ENDO/beta-LPH responses are, like those of ACTH, down-regulated in the course of depressive illness.

Adrenocorticotropic Hormone↗
PubMed1993

Drug use, HIV risk-taking and psychosocial correlates of benzodiazepine use among methadone maintenance clients.

Methadone maintenance clients who used benzodiazepines were compared with other methadone maintenance clients on a range of drug use and psychosocial treatment outcome measures. Despite being on higher methadone doses, benzodiazepine users were more likely to have recently injected, to have used cocaine and amphetamines, to have borrowed or lent used needles and syringes, and to have reported polydrug use in the preceding month. Benzodiazepine users also exhibited higher levels of psychopathology and social dysfunction than other methadone maintenance clients. It is concluded that benzodiazepine-using methadone maintenance clients are a dysfunctional subgroup of the methadone population, who may require more clinical intervention than other clients.

Adolescent↗
PubMed1993

In vitro activity of the benzotriazine dioxide SR 4233 against human tumour colony-forming units.

SR 4233 (3-amino-1,2,4-benzotriazine 1,4-dioxide) is a novel bioreductive agent selectively toxic to hypoxic cells. It is active as a radiation sensitiser in vitro. Using a human tumour cloning system we have studied the effects of SR 4233 against freshly explanted human tumour specimens under hypoxic and non-hypoxic culture conditions. For hypoxic conditions, final concentrations of SR 4233 of 10.0-500 mumol/l were used in short-term (1 h) exposure experiments. Final concentrations in non-hypoxic experiments ranged from 10 to 1350 mumol/l. 25 tumour specimens were tested under each culture condition. Of those, 14 (56%) were evaluable. The most common tumour types recruited included ovarian, non-small cell lung, and breast cancer. A moderate concentration-dependent increase in the frequency of inhibited tumour specimens under non-hypoxic conditions was observed with zero out of 10 sensitive specimens at 10 mumol/l as compared with five out of 14 (36%) sensitive specimens at 500 mumol/l (P < 0.02). However, when hypoxic conditions were used SR 4233 had a profound antitumour activity, (two out of 14 specimens sensitive at 10 mumol/l compared with 10 out of 10 specimens sensitive at 500 mumol/l, P < 0.00005). We conclude that SR 4233 is active against tumour colony-forming units in vitro and that its antitumour activity is greatly increased against hypoxic tumour cells.

Antineoplastic Agents↗
PubMed1993

Urinary red blood cell and cast excretion in normal and hypertensive human pregnancy.

OBJECTIVE: Although the well-recognized pregnancy changes in renal blood flow, cellular function, tubular fluid composition, and flow rates may cause altered excretion rates of formed elements in the urine, relatively little attention has been paid to this in normal pregnancy. The urinary white cell excretion is known to be increased, with loss of the usual relationship between pyuria and urinary infection. Whether the same is true for other formed elements is unknown. Our purpose was to determine normal values for excretion of erythrocytes and casts and to establish whether they became abnormal in women in whom preeclampsia developed. STUDY DESIGN: Study subjects were 174 continuously normotensive pregnant volunteers, 22 women who had preeclampsia, and 8 women who had chronic essential hypertension. Early-morning midstream urine samples were collected at 17 to 20 and at 33 to 36 weeks' amenorrhea after insertion of a vaginal tampon. Urinary microscopy was performed by standard techniques (Kesson et al. Lancet 1978;2:809). RESULTS: The 95th percentile for concentration of erythrocytes was < or = 2500 red blood cells/ml; for casts the concentration was < or = 30 red blood cells/ml in normal pregnancy. Values for those who had preeclampsia and for the small group with chronic essential hypertension were within these limits. CONCLUSION: In an early-morning concentrated urine sample, values of < or = 2500 erythrocytes/ml and < or = 30 hyaline or granular casts per milliliter can be accepted as normal.

Chronic Disease↗