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J Klassen

Publications and source records attributed to J Klassen.

At least 19 recordsLinked to original sources
PubMed1998

Enalapril restores depressed circulating insulin-like growth factor 1 in patients with chronic heart failure.

BACKGROUND: Congestive heart failure (CHF) is characterized by increased activity of the renin-angiotensin system. Recent experimental studies have shown that infusion of angiotensin II results in depressed plasma levels of insulin-like growth factor 1 (IGF-1) and weight loss. We have previously reported that stable patients with CHF have decreased activity of the growth hormone (GH)-IGF1 axis. We have hypothesized, therefore, that angiotensin-converting enzyme (ACE) inhibition therapy should restore GH-IGF1 activity in CHF patients. METHODS AND RESULTS: Nine patients with stable CHF who were taking digitalis and diuretics, New York Heart Association functional class III were studied before and after 8 weeks of therapy with Enalapril (10 mg twice daily). We measured IGF1 levels, radionuclide left ventricular ejection fraction (EF) and peak oxygen consumption (PVO2). We found that 7 of 9 patients had abnormally low levels of IGF1 (0.2-0.5 mU/ml). IGF1 levels reverted to normal after Enalapril therapy (0.36 +/- 0.03 to 0.8 +/- 0.14 mU/ml, P = .004). This was associated with a significant increase in EF (27.4 +/- 1.1 to 31.4 +/- 0.9%) and PVO2 (14.8 +/- 1.2 to 18.6 +/- 1.5 ml/kg/min) values (P < .05). CONCLUSION: Chronic ACE inhibition therapy restored previously reduced IGF1 plasma levels in patients with CHF, most likely by reducing angiotensin II activity.

Adult↗
PubMed1997

Single-agent high-dose melphalan salvage therapy for Hodgkin's disease: cost, safety, and long-term efficacy.

BACKGROUND: Few data are available on the cost, safety, and long-term efficacy of single-agent high-dose melphalan (HDM) followed by autologous bone marrow (ABMT) or blood stem cell (ABSCT) transplantation in the salvage therapy of Hodgkin's disease (HD). PATIENTS AND METHODS: From February 1981 to September 1996, 23 patients with relapsed (n = 15) or refractory (n = 8) HD received salvage therapy with HDM 140-200 mg/m2 followed by non-cryopreserved ABMT (n = 18) or cryopreserved ABSCT (n = 5). The cost of HDM/ABSCT in 1996, from initial consultation until transfer back to referring physician, was determined and compared to the estimate costs of two multi-agent regimens commonly used for HD. RESULTS: HDM was well tolerated with no early transplant-related mortality. The five-year overall and progression-free survival rates were 52% and 50%, respectively. The average total cost in Canadian funds of HDM/ABSCT in 1996 was $34,400/patient. This cost was estimated to be $4,700-6,800 cheaper per patient than the multi-agent high-dose regimens. CONCLUSION: These data suggest that HDM is safe, feasible, active, and reasonably inexpensive salvage therapy for patients with relapsed/refractory HD.

Adolescent↗
PubMed1997

Partially mismatched blood cell transplants for high-risk hematologic malignancy.

Eleven patients with high-risk hematologic malignancy received cryopreserved but otherwise unmanipulated blood cell transplants (BCT) from partially mismatched family members in whom progenitor cells had been mobilized by G-CSF. Donors were mismatched by up to one antigen in the GVH direction and up to three antigens in the rejection direction. Outcomes were compared with those of 22 patients receiving BCT from fully matched donors. Two mismatched patients died without engraftment on day 21 and 32. One had rejected bone marrow from the same donor, the other was mismatched by two antigens in the rejection direction and received the lowest dose of CD34+ cells. Median time to granulocyte engraftment was 21.5 (range 16-33) days for the mismatched group compared with 16 (11-28) days for the matched group (P = 0.01). No correlation was found between CD34+ cell dose and time to granulocyte or platelet recovery. In the mismatched and matched BCT groups respectively, the risk of grade II-IV acute graft-versus-host disease (GVHD) was 73% vs 28% (P = 0.001) and of chronic GVHD 100% vs 78% at 18 months (P = 0.01). The relationship of T cell dose to acute GVHD could only be evaluated in the matched group and no correlation was found. One of 11 mismatched patients and eight of 22 matched patients had relapse or persistent disease. Disease-free survival at 1 year was similar at 55% for mismatched and 50% for matched BCT. These results indicate that allogeneic BCT from partially mismatched family members is accompanied by a high incidence of GVHD but may result in comparable survival to BCT from fully matched donors.

Adolescent↗
PubMed1997

Factors influencing yields of progenitor cells for allogeneic transplantation: optimization of G-CSF dose, day of collection, and duration of leukapheresis.

Mobilization of hematopoietic progenitor cells by G-CSF was attempted on 89 occasions in 85 healthy donors. Three dose ranges of G-CSF were chosen for analysis: low (4-7.4 micrograms/kg), intermediate (7.5-10 micrograms/kg) and high (> 10 micrograms/kg). A target blood level for apheresis of 20 x 10(6)/L CD34+ cells was reached by day 3 in 75 patients (84%) and by day 4 in all but 1 (99%). Target yields above 2.5 x 10(6)/kg for 75 unmanipulated transplants were exceeded in a single collection in 73 donors (97%). Correlation of CD34+ cell yields to blood CD34+ cell level before leukapheresis was moderate only (r2 = 0.32). There was close linear correlation between processed volume and cumulative CD34+ cell yield, with a median r2 value of 0.98 (range 0.74-1.00). Yields of CD34+ cells achieved on day 3 were significantly lower after the high dose than after the intermediate G-CSF dose (21 +/- 3 versus 29 +/- 6 x 10(6)/L blood processed, p = 0.03). After the low dose of G-CSF, yields on day 4 were higher than on day 3 (48 +/- 10 versus 22 +/- 4 x 10(6)/L blood processed, p = 0.01). There was no difference between day 3 and day 4 yields with the intermediate G-CSF dose. In 73 of 93 (78%) leukaphereses, the CD34+ cell yield was more than 100% of the estimated intravascular CD34+ cells at the beginning of collection and ranged up to 342%. These data indicate that a daily dose of 7.5-10 micrograms/kg G-CSF, given as a multiple of 300 and 480 micrograms ampoules, is a convenient regimen giving adequate yields from a single collection on day 3 or 4 in most donors. Measuring blood CD34+ cell levels is of limited value in predicting yields, but monitoring CD34+ cell yields during leukapheresis may help to minimize unnecessary or inefficient collection.

Antigens, CD34↗
PubMed1997

Absence of irreversible rejection in the presence of warm anti-donor-HLA class I cytotoxic IgG antibody.

Since the initial presentation by Kissmeyer-Nielsen and colleagues [1966] and later by Patel and Terasaki [1969], it has been accepted that renal transplantation should not be performed in the presence of cytotoxic alloreactive antibodies of the IgG fraction performed at room temperature against HLA Class I [Braun 1989] antigens. Such antibodies are feared to induce hyper-acute or accelerated rejection because of the presence of HLA Class I antigens on kidney cells. For this reason, the microlymphocytotoxicity crossmatch (XM test: recipient serum reacted against donor lymphocytes as surrogate for HLA antigens) is now universally used before transplantation [Ting 1983]. A positive XM performed against the recipient T lymphocyte at room temperature after treatment of recipient serum with dithiothreitol (DTT), an agent that removes immunoglobulin M, denotes the presence of cytotoxic alloreactive IgG antibodies against the potential donor HLA class I antigen. Herein, we present the case of a patient who developed positive XM test of the IgG isotype against HLA Class I of the donor antigens performed at room temperature seven days after she received a kidney allograft from her daughter. Although the development of a positive XM was associated clinically with acute rejection, the patient responded remarkably well to anti-rejection therapy and maintained excellent graft function thereafter. Thus, strategies to identify the role played by the different IgG isotypes determined against HLA Class I antigens and their relation to irreversible rejection are needed to differentiate between those potential kidney recipients who may benefit from kidney transplantation in the presence of innocent warm IgG subclass antibodies reactive against HLA Class I antigens and those patients who may not.

Adult↗
PubMed1996

Fibronectin fibrils and growth factors stimulate anchorage-independent growth of a murine mammary carcinoma.

Stromal cells are important regulators of mammary carcinoma growth and metastasis. We have previously shown that a 3T3-L1 adipocyte cell line secretes hepatocyte growth factor (HGF), which stimulates proliferation of a murine mammary carcinoma (SP1) in monolayer cultures (DNA Cell Biol. 13, 1189-1897, 1994). We now examine the role of growth factors and the extracellular matrix protein fibronectin in stimulation of anchorage-independent growth of SP1 cells. Purified transforming growth factor-beta (TGF-beta) stimulated significant colony growth in soft agar cultures, whereas HGF had a lesser effect. Analysis by confocal microscopy revealed that carcinoma cell colonies contained extracellular microfibrils composed of fibronectin. Partial depletion of fibronectin from 7% FBS/agar cultures reduced the number of colonies; colony growth could be recovered by adding back exogenous fibronectin. Addition of the 70-kDa N-terminal fragment of fibronectin, which inhibits fibronectin fibril formation, reduced growth of SP1 cell colonies, but an 85-kDa fragment containing the cell binding domain did not inhibit colony growth. These findings indicate that deposition of extracellular fibronectin fibrils is necessary, but not sufficient, for anchorage-independent growth of SP1 mammary carcinoma cells; growth factors are also required. SP1 cells had less fibronectin mRNA and secreted less fibronectin protein under anchorage-independent conditions than under anchorage-dependent conditions, as determined by Northern blotting and immunoprecipitation analysis. Thus, both growth factors (HGF and TGF-beta) and fibronectin may be important regulators of paracrine stimulation by stromal cells of anchorage-independent growth of mammary carcinoma cells.

3T3 Cells↗
PubMed1996

Allogeneic blood cell transplants for haematological malignancy: preliminary comparison of outcomes with bone marrow transplantation.

Twenty-six patients with haematological malignancy received cryopreserved but otherwise unmanipulated blood cell transplants (BCT) from five- or six-antigen matched siblings in whom progenitor cells had been mobilized by G-CSF. Outcomes were compared with a historical control group of 26 BMT patients matched for age and disease status. Granulocyte counts recovered to 0.5 x 10(9)/l in a median of 16 days after BCT compared with 21.5 days after BMT (P = 0.0002). Platelet counts, unsupported for 3 days, reached 20 x 10(9)/l in a median of 14 days vs 20.5 days (P = 0.0003) after BCT compared with BMT in those patients who engrafted. In the BCT and BMT groups, respectively, the risk of grade II-IV acute GVHD was 37 vs 21% (P = 0.16) and of chronic GVHD at 1 year 53 vs 48% (P = 0.9). There was no significant difference in red cell transfusions but BCT patients required fewer platelet transfusions (median 3 vs 5, P = 0.015) and fewer days in hospital (20.5 vs 25, P = 0.02). These results indicate that allogeneic BCT from matched and partially mismatched family donors result in faster engraftment than BMT without a significant increase in GVHD. Allogeneic BCT may prove to be a more tolerable procedure than BMT for both donor and recipient and there are indications of improved cost-effectiveness.

Adolescent↗
PubMed1996

High-dose melphalan +/- total body irradiation and autologous hematopoietic stem cell rescue for adult patients with Ewing's sarcoma or peripheral neuroectodermal tumor.

The role of high-dose therapy and autologous stem cell transplantation (ASCT) in the treatment of patients with Ewing's sarcoma (EWS) remains uncertain. From November 1985 to September 1994, 13 patients aged 16-30 years (median 20.5) received high-dose melphalan (HDM) 140-200 mg/m2 +/- 500 cGy TBI followed by ASCT for relapsed/refractory (n = 4), metastatic (n = 2), or non-metastatic (n = 6) EWS, or for peripheral neuroectodermal tumor (PNET) (n = 1). This regimen was well tolerated with no transplant-related mortality and no toxicity requiring life sustaining measures. Three of the four patients treated for relapsed/refractory EWS had progression-free survivals (PFS) less than 5 months. The only long-term survivor of these four patients received HDM while in complete remission following pulmonary irradiation. Both patients with pulmonary metastases at presentation died just 5 and 6 months post-ASCT. All four patients with non-metastatic, bulky (> 8 cm) osseous EWS progressed at a median of 11 months (range 7-22 months) while the two patients with non-bulky EWS remain progression-free 25+ and 28+ months post-HDM/TBI + ASCT. The 19-year-old patient with a PNET of the thoracoabdominal wall relapsed 4 months post-ASCT. Overall, only three of these 13 patients remain progression-free at 25+, 28+, and 108+ months following HDM +/- TBI and ASCT. In conclusion, HDM +/- TBI did not obviously improve the outcome of these 13 patients relative to that expected following conventional dose therapy alone.

Adolescent↗
PubMed1996

Second allogeneic transplants for leukemia using blood instead of bone marrow as a source of hemopoietic cells.

There is increasing interest in blood cell transplants (BCT) from normal donors as an alternative to BMT. Ten patients with relapsed or persistent leukemia after BMT received intensive cytotoxic conditioning followed by allogeneic BCT. Three BCT were from single-antigen mismatched donors; two of the corresponding recipients had rejected a BMT from the same donor. Two patients received BCT from a different donor (one matched, one single-antigen mismatched). The other six BCT were from the same, fully matched, bone marrow donors. Donors were given G-CSF to mobilize progenitor cells which were collected by a single 2-4 h leukapheresis. Methotrexate, CsA and folinic acid were used for GVHD prophylaxis for all transplants but CsA was discontinued sooner after BCT than after BMT. One patient died without engraftment having rejected a BMT from the same single-antigen mismatched donor 4 years previously. Nine patients had granulocyte recovery at a median of 14 days, up to 6 days faster than with their previous BMT. Platelet recovery was also 2-6 days faster than with BMT in four previously engrafting patients. Four patients died without platelet recovery after BCT within a year of BMT, three of treatment-related toxicity and one of relapse. Two patients developed grade II acute GVHD. Of six patients given BCT more than a year from BMT, four, all with acute leukemia, survive 7, 14, 29 and 29 months after BCT and one relapsed at 7 months. All four survivors developed chronic GVHD. These results indicate that BCT may be useful therapy for relapse occurring more than a year after BMT.

Adolescent↗
PubMed1996

Localization of platelet-derived growth factor beta receptor expression in the periepithelial stroma of human breast carcinoma.

Platelet-derived growth factor (PDGF) BB is secreted by most human breast carcinoma cells; however, only recently have PDGF beta receptors been demonstrated in malignant breast tissue. In the present study, the tissue localization of PDGF beta receptor expression was studied in human breast carcinoma and nonmalignant breast tissues stained using both immunofluorescence and immunoperoxidase techniques. We examined a total of 29 cases of breast carcinomas, which showed both in situ and invasive components. PDGF beta receptor staining was localized in the periepithelial stroma and was particularly intense in regions immediately adjacent to carcinoma in situ components in all tumors examined. A diffuse low level of PDGF beta receptor staining was seen throughout the stroma of eight nonmalignant breast tissues as well as of nonmalignant regions of tumor tissues. Image analysis was used to assess the coincidence of staining of PDGF beta receptor with epithelial or stromal cells in 13 of the 29 tumor tissues studied. Less than 5% of malignant ductal epithelium or myoepithelium showed PDGF beta receptor staining. Analysis with stromal cell type-specific markers indicated significant localization of PDGF beta receptor primarily within alpha smooth muscle actin-staining cells (32%) and vascular endothelial cells (41%) in the periepithelial stroma. PDGF beta receptor positivity was strongly associated with periepithelial stromal cells adjacent to the basement membrane surrounding regions of carcinoma in situ but was less intense in regions of invasive carcinoma where basement membrane was degraded. The absence of PDGF beta receptors on carcinoma cells and their presence in the surrounding stroma suggest a paracrine stimulation of adjacent stromal tissue by malignant epithelial cells in human breast tumors.

Actins↗
PubMed1995

Effect of glucocorticoids on serum osteocalcin concentration in horses.

The effects of dexamethasone (0.2 mg/kg of body weight; IV, IM, and PO) and methylprednisolone acetate (120 mg given intra-articularly) on serum osteocalcin and cortisol concentrations were studied in 6 horses. Serum osteocalcin and cortisol concentrations were serially monitored after each treatment. A significant (P < 0.05) decrease in serum osteocalcin and cortisol concentrations was observed from 12 to 24 and 2 to 48 hours, respectively, after IV and IM administrations of dexamethasone. Serum osteocalcin and cortisol concentrations were significantly decreased from 6 to 48 and 3 to 72 hours, respectively, after oral administration. In contrast, a change in serum osteocalcin concentration was not detected after intra-articular administration of methylprednisolone. Oral, IV, or IM treatment with 0.2 mg of dexamethasone/kg caused a decrease in serum osteocalcin concentration in horses.

Animals↗
PubMed1995

Collection of progenitor cells for allogeneic transplantation from peripheral blood of normal donors.

Fourteen donors were given recombinant G-CSF to mobilize progenitor cells. Circulating CD34+ cells were monitored daily and leukapheresis was performed at 3-5 days when the level exceeded 20 x 10(6)/L. Monitoring of CD34+ cells collected at intervals during apheresis gave results within 20 min. Yields of 2.6-7.4 x 10(6) per kg recipient body weight were achieved in single aphereses of 2-4 h in all but two cases where the donor was substantially smaller than the recipient. These products were sufficient to establish engraftment, at least of granulocytes, in 11 five or six antigen matched recipients with high risk malignancy. Despite some complications donors tolerated the procedure well and the five individuals who had previously given marrow preferred these manoeuvres to bone marrow harvest. The ability to monitor CD34+ cells rapidly in the circulation and leukapheresis product facilitates an efficient collection technique for allogeneic BCT donors. Adequate yields could probably be achieved by a single harvest on days 2-4 in most donors.

Acute Disease↗
PubMed1995

Challenging consults: application of principles of physiology and biochemistry to the bedside. Osmotic diuresis: the importance of counting the number of osmoles excreted.

Polyuria is usually the result of a water diuresis or an osmotic diuresis. Traditionally, the assessment of the extracellular fluid (ECF) volume and the concentration of Na+ in plasma is sufficient to differentiate between the two. We present a case and our approach, which is based on calculations and quantitation of osmoles, to demonstrate the utility of this approach. A patient with diabetes mellitus, human T-cell lymphocyte virus, type 1 (HTLV-1) associated lymphoma, and hypercalcemia presented with marked ECF volume contraction and polyuria. A spot urine osmolality was 567 mOsm/kg H2O in the face of urine output of approximately 6 L/d. The initial diagnosis was an osmotic diuresis. However, a quantitative analysis revealed the enormous number of osmoles could not be accounted for physiologically. Hence, we postulated a water diuresis to be the cause of the polyuria. To confirm this hypothesis, we found that at different times during his hospitalization, the urine specific gravity ranged from 1.005 to 1.022, and urine output varied markedly over 8-h periods. Despite a plasma sodium of 147 mmol/L, the patient did not complain of thirst. Taken together, this suggested the presence of a hypothalamic lesion which caused central diabetes insipidus with variable output of antidiuretic hormone together with a blunted thirst response. Illustration of the utility of a quantitative approach to polyuria is the focus of the discussion.

Chlorides↗
PubMed1993

Post-transplant conversion from cyclosporin to azathioprine: effect on cardiovascular risk profile.

The benefits of long-term cyclosporin (CyA) therapy are not yet established and must be weighed against its toxicity. We studied cardiovascular risk factors in 25 patients who received a kidney transplant between 1985 and 1989 and in whom CyA was discontinued. The protocol for discontinuing CyA involved starting azathioprine (Aza) and then weaning CyA over 6 weeks without changing the prednisone dose. Parameters collected from the patients' charts 3 months before (pre) and 3 months after conversion (post) and at the most current follow-up (cur) included serum creatinine, cholesterol, blood pressure, and anti-hypertensive medication. The severity of the hypertension was graded, based on a hypertension index reflecting the nature and dose of the anti-hypertensive medication. Of the 25 patients in whom CyA was discontinued, 2 experienced a rejection episode during conversion and were switched back to CyA; 1 patient had a rejection episode after conversion but remained on Aza. Converted patients demonstrated improved renal function (1/Cr pre 0.69 +/- 0.20, post 0.84 +/- 0.23, P < 0.05), lower serum cholesterol levels (pre 6.8 +/- 1.0, post 5.8 +/- 1.2, P < 0.05), lower mean arterial pressure (pre 111 +/- 14, post 102 +/- 8, P < 0.05) and a lower hypertension index (pre 2.45 +/- 2.77, cur 1.62 +/- 1.70, P < 0.05). Although conversion may carry some risk of acute rejection, it improves graft function and the cardiovascular risk profile significantly.

Adult↗
PubMed1991

Decreased hospitalization and increased height velocity in focal segmental glomerulosclerosis responsive to ciclosporin A.

Eleven pediatric patients with nephrosis and focal segmental glomerulosclerosis were treated with long-term (8-38 months) ciclosporin A in combination with steroids. All had abnormal height-velocity curves and multiple hospitalizations for complications of nephrosis. Eight patients attained remission with a dramatic improvement in growth and decrease in necessity for hospitalization for therapy of nephrosis complications, while maintaining adequate renal function. Three nonresponders developed end-stage renal disease. Long-term ciclosporin A therapy may be of benefit in steroid-resistant nephrosis in childhood.

Child↗