Biomedical subjects

J M Thompson

Publications and source records attributed to J M Thompson.

At least 73 records · Page 4Linked to original sources

PubMed1998

The effect of sire breed on the melting point and fatty acid composition of subcutaneous fat in steers.

Fatty acid composition and the melting point of subcutaneous fat was determined in 18 Hereford, 25 Brahman x Hereford, 22 Simmental x Hereford, and 15 Friesian x Hereford steers that were grown out on pasture at two sites and slaughtered when the mean weight of the Herefords at each site was ca. 450 kg. Multivariate and univariate analyses tested the relations of fatty acid composition, degree of saturation, and melting point with sire breed, environment, age, and carcass characteristics. Hereford and Brahman steers were fatter than the Simmental and Friesian steers. Fat from Brahman-sired steers had a melting point 2.5 degrees C lower than fat from the Bos taurus-sired steers at the same age and had a higher proportion of unsaturated fatty acids, independent of variation in carcass weight and fatness. Melting point and degree of saturation decreased as age increased. Step-down discriminant analyses identified a set of three acids (14:0, 16:0, and 17:1) that differed among sire breeds, independent of differences in melting point: the acids 14:0 and 16:0 discriminated between Brahman and Bos taurus steers and 17:1 between Hereford and Simmental and Friesian steers. Increase in fatness was associated with an increase in 17:1, but, at the same fatness, no acids discriminated among the Bos taurus-sired steers. The use of Bos indicus cattle or their crossbreeds in situations in which hard-setting fat is likely may mitigate the problem.

Adipose Tissue↗

PubMed1997

Management of osteoarthritis in the primary-care setting: an evidence-based approach to treatment.

The most prevalent musculoskeletal condition that results in joint pain is osteoarthritis (OA), with nearly 70% of the population >65 years of age demonstrating radiographic evidence of this disease. The knee is the joint commonly affected. Therapy for OA of the knee is directed at decreasing joint pain and increasing function and includes both pharmacologic and nonpharmacologic interventions. Pharmacologic therapy begins with analgesic medications and proceeds to topical analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) as needed. Intra-articular injections of corticosteroids can relieve pain and inflammation but the effect is of very short duration and such therapy should only be employed infrequently. Nonpharmacologic therapy should include patient education, weight loss if clinically indicated, physical therapy directed at maintaining joint mobility and strengthening muscle groups or an organized low-impact exercise program, and assistive devices as needed. Total joint replacement appears to be a successful therapy when joint pain severely limits a patient's ability to function. Experimental therapies to modify pain and function in OA patients include intra-articular injections of hyaluronan or arthroscopic joint lavage and debridement. In summary, both pharmacologic and nonpharmacologic measures can contribute to the treatment of pain from OA of the knee.

Analgesics↗

PubMed1997

Cerebral noradrenaline spillover and its relation to muscle sympathetic nervous activity in healthy human subjects.

Studies using internal jugular vein blood sampling in human subjects have demonstrated the release of noradrenaline from the brain and have provided a link between central nervous system noradrenergic neuronal activity and renal, cardiac and total body sympathetic activity. The aim of this study was to further categorise the dependence of regional sympathetic nervous function on central nervous system noradrenergic neuronal processes by combining measures of internal jugular venous noradrenaline spillover, as an indicator of brain noradrenaline release, and cerebral blood flow scans with measures of the overall integrated neuronal firing rate for the body as a whole, the spillover of noradrenaline into the coronary sinus and with measurements of resting muscle sympathetic nerve activity. Positive veno-arterial plasma noradrenaline gradients were found across the brain, with the plasma concentration being 17 +/- 3% (p < 0.01) greater in the internal jugular vein. Linear regression analysis revealed a significant relationship between the degree of muscle sympathetic nerve activity and the spillover of noradrenaline from subcortical brain regions (y = 0.1 x + 16.0; r = 0.81, p < 0.02). The rate of spillover of noradrenaline for the body as a whole also bore a significant association with the rate of subcortical noradrenaline spillover (y = 0.01x + 2.33; r = 0.71, p < 0.05). Cortical noradrenaline spillover was not related to any of the sympathetic nervous system parameters measured in this study. The demonstration of a direct relationship between the rate of peroneal nerve firing and the spillover of noradrenaline from subcortical brain regions provides further support for the concept of central nervous system noradrenergic cell groups behaving in a sympathoexcitatory role.

Adult↗

PubMed1997

Changes in diameter of the abdominal aorta with age: an epidemiological study.

Rupture of abdominal aortic aneurysms is a major cause of death for men who are over 60 years old. This study invited 13,000 men aged 60 to 75 years, within the Birmingham conurbation, to have an ultrasound scan of the abdominal aorta. The scan was performed at the patients' own General Practitioner's surgery; 10,061 men were scanned. Only 3% of this population were found to have large aneurysms. An analysis of the distribution of aortic diameters in this population shows that for diameters less than 40 mm, changes in the diameter with age (previously attributed to the growth of small aneurysms) occurs for up to 25% of the population although the median diameter for each year group, 21 mm, does not increase with age. This analysis suggests that the threshold diameter at which the aorta is categorized as abnormal should be related to age, especially by those undertaking mass screening.

Aged↗

PubMed1997

Not all postmenopausal women on chronic steroid and estrogen treatment are osteoporotic: predictors of bone mineral density.

Chronic steroid use results in osteoporosis, and postmenopausal women are believed to be at a high risk for steroid-induced bone loss. The purpose of this study was to determine predictors of bone mineral density (BMD) in postmenopausal women on both chronic steroid and hormone replacement therapy. Seventy-six postmenopausal women (> or = 3 years postmenopausal, > or = 2 years of steroid treatment of > or = 5 mg/day of prednisone, and > or 1 year of hormone replacement therapy) were recruited into this study. Measurements of BMD of the lumbar spine and femoral neck were obtained in all subjects. Risk factors for osteoporosis were obtained by questionnaire. Discriminant analysis was performed to determine predictors of BMD. Osteoporosis, defined by a T score of < -2.5, was present in the lumbar spine or femoral neck in 34 of the 76 subjects. Based on these criteria, women with osteoporosis were significantly older, were more years postmenopausal, and had a lower body mass index (BMI) than women who did not have osteoporosis. Predictors of osteoporosis for both the femoral neck and spine included a low BMI (P < 0.05), more years postmenopausal (P < 0.01), and more years on steroids (P < 0.01). Low BMI was the only significant predictor of osteoporosis in the lumbar spine (P < 0.05), whereas for the femoral neck both years on steroids (P < 0.05) and BMI (P < 0.05) were significant predictors of low BMD. In summary, not all postmenopausal women on chronic steroid and hormone replacement therapy are osteoporotic but a low BMI, more years on steroids, and more years postmenopausal were significant predictors of osteoporosis in these subjects.

Absorptiometry, Photon↗

PubMed1997

Vessel wall and flow characteristics after carotid endarterectomy: eversion endarterectomy compared with Dacron patch plasty.

OBJECTIVES: Experimental studies have demonstrated that decreases in vessel wall compliance and increases in turbulence may contribute to (re)stenosis. We studied vessel wall and flow characteristics after endarterectomy with Dacron patch plasty and after eversion endarterectomy, and compared those findings with the characteristics of non-stenotic, unoperated carotid arteries (controls). METHODS: Seventy-four patients who underwent 84 carotid endarterectomies were studied postoperatively by ultrasonography (2-24 months) Recorded variables included the diameter of the bulb, strain, elastic modulus (stiffness), and presence of turbulent flow. RESULTS: The vessel wall and flow characteristics of the two groups differed significantly. The diameter was higher and the strain lower in Dacron patch plasty than in controls; eversion endarterectomy did not differ from controls. The elastic modulus was higher (stiffer) in Dacron patch plasty than in eversion endarterectomy; neither Dacron patch plasty nor eversion endarterectomy differed significantly from controls. The stiffness index was not significantly different between the groups. Turbulence was present in Dacron patch plasty and eversion endarterectomy when compared with controls. CONCLUSION: In diameter, strain and stiffness, the operated carotid artery resembles the non-stenotic, unoperated artery more closely after eversion endarterectomy than after Dacron patch plasty.

Aged↗

PubMed1997

Single-agent paclitaxel in patients with previously untreated stage IV epithelial ovarian cancer. London Gynaecological Oncology and North Thames Gynaecological Oncology Groups.

The aim of this study was to evaluate the efficacy of high-dose paclitaxel in patients with previously untreated stage IV epithelial ovarian cancer. Paclitaxel was administered intravenously over 3 h at a dose of 225 mg m(-2) on a 21-day cycle for six courses. Thirty-six patients were entered into this study; all 36 were assessed for toxicity and 33 patients were evaluable for response. One patient had a complete response and 12 patients had partial responses (overall response rate 39.4%, 95% CI 23-58%). The overall median duration of response was 9 months (range 3.5-23+ months). The response rate to carboplatin following failure of paclitaxel within 1 year of stopping therapy was 57% (four out of seven patients). The median survival of patients was 17.2 months. The main toxicity encountered was neutropenia which was WHO grade 3 in 11 patients (31%) and WHO grade 4 in seven patients (19%). Granulocyte colony-stimulating factor (GCSF) was not given to any patient during the study. Other toxicities were: grade 3/4 infection (11%) and nausea and vomiting (11%); grade 3 bone pain (22%), fatigue (14%), diarrhoea (3%), myalgia/arthralgia (3%) and dry eyes (3%). Transient peripheral neuropathy occurred in 16 patients (44%), and alopecia was encountered in most patients (grade 2/3, 78%). Paclitaxel given at 225 mg m(-2) to patients with stage IV epithelial ovarian cancer is active, well tolerated and does not require GCSF support.

Adult↗

PubMed1997

Diagnosis and carrier detection of chronic granulomatous disease in five families by flow cytometry.

BACKGROUND: The application of flow cytometric assays, for determination of phagocyte respiratory burst (ROB) activity, to the investigation of chronic granulomatous disease (CGD) may lead to improved laboratory detection of patients and carriers and indicate the nature of the molecular defect. To evaluate the diagnostic capability of flow cytometry an investigation of 5 CGD families was undertaken. METHODS: Phorbol myristate acetate (PMA)-induced neutrophil ROB was determined using dihydrorhodamine 123 (DHR) and flow cytometric analysis in 26 members of 5 CGD families (2: X-CGD; 3: autosomal recessive CGD). RESULTS: Neutrophils from X-CGD patients displayed absence of reactivity. Female carriers demonstrated dual fluorescence peaks of high and low intensity indicative of normal and abnormal populations, respectively. Normal ROB activity was observed in a boy whose X-CGD was successfully treated by bone marrow transplantion. Reduced ROB activity was observed in 3 patients with autosomal-recessive CGD compared with their parents and siblings. The patterns of flow cytometric reactivity correlated with the different molecular defects identified. Absence of the p22phox membrane component of the NADPH oxidase complex resulted in a significantly reduced level of respiratory burst activity which was comparable to that observed in X-CGD, whereas reduced but detectable levels of respiratory burst activity were observed in a patient with diminished levels of p22phox and in a patient with deficiency of the cytosolic p47phox component. CONCLUSIONS: The DHR flow cytometric assay offers a sensitive diagnostic screening test for CGD and furthermore may provide an indication of the likely underlying molecular defect.

Adolescent↗

PubMed1997

Association of ownership and system affiliation with the financial performance of rehabilitation hospitals.

This study used a cross-sectional design in which regression models were used to test the association of ownership and system affiliation of private rehabilitation hospitals with profit, revenue and expense measures. The study also examined the association of ownership and system affiliation with other choice variables. The study found that new for-profit rehabilitation hospitals had higher revenues and expenses than older non-profit rehabilitation hospitals. In addition, new for-profit hospitals charged more for their ancillary services and treated more of their patients on an inpatient basis. Study findings show higher revenues and expenses per adjusted discharge for new for-profit facilities. Given the cost-based system of reimbursement for Medicare, there appears to be a strong incentive for new for-profits to maximize costs.

Cross-Sectional Studies↗

PubMed1997

Risk factors for sudden infant death syndrome following the prevention campaign in New Zealand: a prospective study.

OBJECTIVES: To identify the risk factors for sudden infant death syndrome (SIDS) following a national campaign to prevent SIDS. METHODS: For 2 years (October 1, 1991 through September 30, 1993) data were collected by community child health nurses on all infants born in New Zealand at initial contact and at 2 months. RESULTS: There were 232 SIDS cases in the postneonatal age group (2.0/1000 live births) and these were compared with 1200 randomly selected control subjects. Information was available for 127 cases (54.7%) and 922 (76.8%) of controls. The previously identified modifiable risk factors were examined. The prevalence of prone sleeping position of the infant was very low (0.7% at initial contact and 3. 0% at 2 months), but was still associated with an increased risk of SIDS. In addition, the side sleeping position was also found to have an increased risk of SIDS compared with the supine sleeping position (at 2 months: adjusted odds ratio (OR) = 6.57; 95% confidence interval (CI) = 1.71, 25.23). Maternal smoking was found to be the major risk factor for SIDS. Bed sharing was also associated with an increased risk of SIDS. There was an interaction between maternal smoking and bed sharing on the risk of SIDS. Compared with infants not exposed to either bed sharing or maternal smoking, the adjusted OR for infants of mothers who smoked was 5.01 (95% CI = 2.01, 12.46) for bed sharing at the initial contact and 5.02 (95% CI = 1.05, 24. 05) for bed sharing at 2 months. In this study breastfeeding was not associated with a statistically significant reduction in the risk of SIDS. The other risk factors for SIDS identified were: unmarried mother, leaving school at a younger age, young mother, greater number of previous pregnancies, late attendance for antenatal care, smoking in pregnancy, male infant, Maori ethnicity, low birth weight, and shorter gestation. CONCLUSIONS: After adjustment for potential confounders, prone and side sleeping positions, maternal smoking, and the joint exposure to bed sharing and maternal smoking were associated with statistically significant increased risk of SIDS. A change from the side to the supine sleeping position could result in a substantial reduction in SIDS. Maternal smoking is common in New Zealand and with the reduction in the prevalence of prone sleeping position is now the major risk factor in this country. However, smoking behavior has been difficult to change. Bed sharing is also a major factor but appears only to be a risk to infants of mothers who smoke. Addressing bed sharing among mothers who smoke could reduce SIDS by at least one third. Breastfeeding did not appear to offer a statistically significant reduction in SIDS risk after adjustment of potential confounders, but as breastfeeding rates are comparatively good in New Zealand, this result should be interpreted with caution as the power of this study to detect a benefit is small.

Beds↗

PubMed1997

Twenty years of outpatient respiratory syncytial virus infection: a framework for vaccine efficacy trials.

BACKGROUND: Respiratory syncytial virus (RSV) is the most important viral respiratory pathogen of infancy and childhood. Much has been written about inpatients with severe disease. Inpatients, however, represent only a minority of RSV-infected children. We studied the characteristics of symptomatic outpatient RSV infection in healthy children to gain a better understanding of RSV disease and to provide a background for the testing of intervention strategies in children without high-risk conditions. METHODS: A total of 1113 children were followed during 20 consecutive RSV seasons. Signs and symptoms of respiratory infection were monitored. Cultures were obtained for febrile upper respiratory infection, acute otitis media, and lower respiratory infection (LRI). Rates of febrile upper respiratory infection, acute otitis media, LRI, and hospitalization were calculated. Given those rates, numbers of children needed to demonstrate efficacy of a vaccine product were calculated. RESULTS: Mild disease from RSV infection lacked some of the classic features of RSV infection seen in hospitalized children. Involvement of the lower respiratory tract was, however, noted to be much higher in RSV infection than it was in infection with other viral respiratory pathogens. LRI was, therefore, considered the best candidate endpoint for vaccine trials. A product with 60% efficacy could be proven, with a power of 0.8, to be efficacious with as few as 1500 infants. CONCLUSIONS: RSV infection is common and often involves the lower respiratory tract, even in outpatients. Our 20-year study of RSV infection provides a basis for calculation of sample sizes to be used in trials of vaccine candidates.

Ambulatory Care Facilities↗

PubMed1996

Renal noradrenaline spillover correlates with muscle sympathetic activity in humans.

1. To study the relationship between indices of resting sympathetic traffic in nerves to skeletal muscles and the kidneys, simultaneous measurements were made of muscle sympathetic activity in the peroneal nerve and renal noradrenaline spillover in ten healthy normotensive males aged 18-69 years (mean 42 years). 2. Group mean levels (+/-S.D.) of muscle sympathetic activity and renal spillover were 22 +/- 17 bursts min-1 and 105 +/- 49 ng min-1, respectively. There were significant positive correlations between individual values of muscle sympathetic activity and renal noradrenaline spillover (r = 0.76, P < 0.01) and similarly between muscle sympathetic activity and renal venous plasma concentration of noradrenaline(r = 0.79, P < 0.007). 3. The results indicate that, although the sympathetic system has the capacity for selective activation of different subdivisions, in healthy human subjects resting traffic is similar or proportional in sympathetic nerves to skeletal muscles and the kidney.

Adult↗

PubMed1996

Infant room-sharing and prone sleep position in sudden infant death syndrome. New Zealand Cot Death Study Group.

BACKGROUND: There is evidence that the risk of sudden infant death syndrome is lower among ethnic groups in which parents generally share a room with the infant for sleeping. We investigated whether the presence of other family members in the infant's sleeping room affects the risk of the sudden infant death syndrome. METHODS: The case-control study covered a region with 78% of all births in New Zealand during 1987-90. Home interviews were completed with parents of 393 (81.0% of total) babies who died from the sudden infant death syndrome aged 28 days to 1 year and 1592 (88.4% of total) controls, selected from all hospital births in the study region. FINDINGS: The relative risk of sudden infant death for sharing the room with one or more adults compared with not sharing was 0.19 (95% CI 0.08-0.45) for sharing at night during the last 2 weeks and 0.27 (0.17-0.41) for sharing in the last sleep, after control for other confounders. Sharing the room with one or more children did not affect the relative risk (1.25 [0.86-1.82] for sharing during last 2 weeks; 1.29 [0.85-1.94] for sharing in last sleep). There was a significant interaction (p = 0.033) between not sharing the room with an adult and prone sleep position in the last sleep. Compared with infants sharing the room with an adult and not prone, the multivariate relative risk was 16.99 (10.43-27.69) for infants not sharing with an adult and prone, 3.28 (2.06-5.23) for infants sharing the room and prone, and 2.60 (1.58-4.30) for infants not sharing the room and not prone. The interaction between adult room-sharing and prone sleep position suggests that both exposures may affect the risk of sudden infant death syndrome through a common mechanism. INTERPRETATION: We recommend that infants sleep in the same bedroom as their parents at night to reduce the risk of sudden infant death syndrome.

Adult↗

PubMed1996

Cytosolic inactivation of translocated neutrophil plasma membrane protein tyrosine phosphatase.

Phosphotyrosine phosphatases (PTPases) regulate cellular metabolic activation by reversing the effects of tyrosine kinases activated earlier in intracellular signaling pathways. We coupled fluorescence-activated cell sorter analysis using anti-CD45 monoclonal antibody with direct measurements of enzyme activity in resolved subcellular fractions to define mechanisms that potentially regulate the availability and activity of CD45-PTPase on neutrophil plasma membranes. Neutrophils in freshly obtained blood as well as neutrophils freshly isolated from blood were found to possess detectable levels of plasma membrane CD45 as assessed by immunofluorescence. However, plasma membranes from these cells were essentially devoid of PTPase catalytic activity, which was largely confined to the specific granules. Granulocyte-macrophage colony-stimulating factor (GM-CSF) upregulated both the catalytic and antigenic components of CD45-PTPase on the plasma membrane of these cells. Upregulation was associated with a shift in the particulate subcellular PTPase catalytic activity from the specific granule fraction to the plasma membrane fraction. The tyrosine kinase inhibitor genistein abrogated GM-CSF-promoted upregulation of plasma membrane CD45 PTPase but did not prevent the GM-CSF-dependent decrease in specific granule catalytic activity. Anti-CD45 antibody immunoprecipitated PTPase activity from both specific granules of resting cells and plasma membranes of GM-CSF-treated cells. However, antiphosphotyrosine immunoprecipitated only activity that had translocated to the plasma membrane, suggesting a role for CD45 phosphorylation in translocation. Western analysis confirmed the tyrosine phosphorylation of CD45 in plasma membranes of GM-CSF-treated neutrophils. Preincubation of plasma membranes of GM-CSF-stimulated neutrophils with cytosol from resting cells resulted in a time- and temperature-dependent loss in membrane PTPase as a consequence of the effects of a cytosolic inactivator. Cytosol obtained from stimulated neutrophils possessed substantially reduced levels of this PTPase inactivator. We conclude that activity of the catalytic component of membrane PTPase in circulating neutrophils is regulated by a cytosolic inactivator. Upon stimulation, intact CD45 PTPase is incorporated into the plasma membrane by a process that requires tyrosine phosphorylation. As a result of inhibition of the cytosolic inactivator, the translocated PTPase expresses full activity, thereby amplifying the potential regulatory influence of the enzyme on the cells' functional response.

Antibodies, Monoclonal↗

PubMed1996

A phase II study of single agent paclitaxel in patients at first relapse following initial chemotherapy for breast cancer.

This study was initiated to evaluate the safety and efficacy of 3-weekly paclitaxel given at 225 mg/m2 over 3 hours without colony stimulating factor support in patients at their first relapse following adjuvant therapy for breast cancer. Thirty patients were entered into the study; all were assessable for response and toxicity. All patients had received adjuvant/neo-adjuvant chemotherapy; 22 patients had had prior hormonal therapy and 26 previous adjuvant radiotherapy. The group was characterized by a short time to first relapse (median 7.5 months (range 2-43)) and widespread disease, with 22 patients having multiple disease sites including: nodes (43%), skin and soft tissue (43%), liver (40%), lung (37%) and bone (50%). A total of 219 cycles of paclitaxel were given, with a median of eight per patient. The major non-haematological toxicities were: grade 3 alopecia (82% cycles), grade 2/3 arthralgia/myalgia (26%), grade 2/3 fatigue (16%) and grade 2/3 peripheral nervous system toxicity (12%). Haematological toxicity was mainly neutropenia of short duration, with grade 4 counts documented in 16% of cycles. Thrombocytopenia was minimal and there were no significant hypersensitivity reactions. The objective response rate was 60% (95% CI 42.5-77.5) with one complete response and 17 partial responses. The median duration of overall response was 30 weeks (range 15-75+ (95% CI 25-33)) with a median survival time for all patients of 42 weeks (range 1-124+). This study demonstrates that paclitaxel 225 mg/m2 is well tolerated as a 3-hour infusion and can be given safely in an outpatient setting without routine use of granulocyte colony stimulating factor. The response rate is encouraging and shows that this regimen is effective in this poor prognosis patient population.

Adult↗

PubMed1996

ET nursing education in Australia.

Australia is comparable in size to the United States, but its population is far smaller, approximately 17 million. Australia is technologically advanced and has a high standard of health care, in which ET nursing has always been considered a specialist nursing role. Although Australia is historically linked with England, formation of closer ties with geographic neighbors, such as Southeast Asia, New Zealand, and the Pacific nations, is ongoing. This article describes some relevant aspects of the Australian context and considers the past, present, and expected future trends for ET nurse education in Australia, from the first program in 1971 to current World Council of Enterostomal Therapy-recognized programs teaching students from as far away as Japan, Israel, Singapore, Malaysia, New Zealand, China, Russia, and New Guinea. The content of the programs has progressively broadened in recognition of the expanded scope of practice, and this trend will undoubtedly continue. ET nursing should remain, however, a distinct nursing specialty practice in Australia.

Accreditation↗

PubMed1996

Growth factor induction of cytosolic protein tyrosine kinase activity in human haemopoietic progenitor cells isolated by flow cytometry.

We employed a highly sensitive method to assay protein tyrosine kinase activity in extracts of subpopulations of CD34+ bone marrow progenitor cells isolated by fluorescence activated cell sorting in an attempt to better define how growth-factor induction of enzymatic activity relates to progenitor cell maturation. FACS analysis confirmed that, under the conditions employed, essentially all of the CD34+ cells in adult human marrow that lacked the CD38 antigen were devoid of the myeloid maturation marker CD33 as well as the lineage antigens: CD10, 13, 14, 15, 16, 19, 71 and glycophorin A. A variable portion (50-90%) of these CD34+, CD38- progenitor cells expressed HLA-DR. CD34+, CD38- cells that did not express HLA-DR were found to lack detectable levels of either membrane or cytosolic tyrosine kinase activity. HLA-DR+ progenitor cells that lacked CD38 possessed elevated levels of cytosolic tyrosine kinase activity but only low levels of plasma membrane activity. In contrast, CD34+ cells that expressed CD38 (and HLA-DR) possessed high levels of membrane-associated tyrosine kinase activity. A cocktail of haemopoietic growth factors that included IL-3, IL-6 and stem cell factor effectively induced tyrosine kinase activity in CD34+, CD38-, HLA-DR- progenitor cells. Growth factor induction of tyrosine kinase activity in these cells was not inhibited by actinomycin D or cyclohexamide. Most of the tyrosine kinase activity induced by these growth factors was recovered from the cytosolic fraction of disrupted cells. Thus, induction of cytosolic tyrosine kinase activity is an early event in the response of uncommitted haemopoietic cells to haemopoietic growth factors. Subsequent activation of membrane tyrosine kinases may initiate key transduction processes as these cells begin to differentiate.

Antigens, CD↗

PubMed1996

Impaired stem cell collection by consecutive courses of high-dose mobilizing chemotherapy using cyclophosphamide, etoposide, and G-CSF.

Tandem cycles of myeloablative chemotherapy can increase dose intensity and total dose of chemotherapy, but sufficient numbers of progenitor cells must be collected to ensure hematologic recovery after each treatment. This study was undertaken to determine if two courses of mobilizing chemotherapy given 4 weeks apart using cyclophosphamide 4000 mg/m2 and etoposide 400 mg/m2, combined with G-CSF 5-10 mg/kg on days 3-16 could each provide sufficient numbers of peripheral blood progenitor cells to support tandem cycles of myeloablative chemotherapy in 20 patients with stage IV breast cancer. Leukapheresis of blood with WBC > 1000/mm3 was performed daily for up to five collections (days 12-16), and mononuclear cells, CFU-GM, and CD34+ cells were compared between the first and second collections. The second course of mobilizing treatment resulted in similar numbers of mononuclear cells collected but far fewer CFU-GM and CD34+ progenitor cells. This prevented using the second collection of progenitor cells as the sole source for the second transplant. The data suggest that a second course of cyclophosphamide, etoposide, and G-CSF given 4 weeks after the first leads to progenitor cell depletion, and efforts to increase the yield of blood-derived progenitors should focus on the initial mobilizing procedure.

Adult↗