NANOCIS®: Possible errors in the summary of product characteristics quality control method and a suggested alternative method.

BACKGROUND: Determination of the radiochemical purity of [99mTc]NANOCIS® was performed using the procedure described in the Summary of Product Characteristics (SPC). In contrast to the clinical findings of thyroid gland accumulation indicating free [99mTc] pertechnetate, the QC results showed no free [99mTc]pertechnetate. This discrepancy prompted us to further investigate the described QC procedure. The aim of our study is to develop a correct QC procedure for [99mTc]NANOCIS®. METHOD AND MATERIALS: After 99mTc-labelling performed in accordance with the SPC, QC was performed on two stationary phases (Whatman No. 1 and ITLC-SA) with both wet and dry application spots. RESULTS: All QC samples prepared using the method described in the SPC (Whatman No. 1 with dry application spot) indicated an acceptable labelling with a radiochemical purity over 99 %. The QC methods performed using non-SPC described methods (Whatman No. 1 with wet application spot, ITLC-SA with wet and dry application spot), show more impurities, resulting in radiochemical purity ranging between 68 % and 99 %. All results from the three QC procedures not outlined in the SPC resulted in comparable results. When comparing the QC results with imaging of the thyroid gland, if the correct TLC method is used, a clear connection was observed between low radiochemical purity, as a result of free [99mTc]pertechnetate present in the prepared radiopharmaceutical, and visualisation of the thyroid gland, due to thyroid uptake of the free [99mTc]pertechnetate. CONCLUSION: Drying the application spot on Whatman No. 1 paper indicates erroneous high labelling. To obtain a correct QC result, either an analytical method using Whatman No. 1 papers without drying of the application spot or a method using instant thin layer chromatography with a silica acid coating (ITLC-SA) should be used.

Mini Nutritional Assessment Short-Form (MNA-SF) Predicts Institutionalisation in an Intermediate Post-Acute Care Setting.

OBJECTIVES: The aim of the study was to investigate whether nutritional status as measured by the Mini Nutritional Assessment Short-Form (MNA-SF) predicts level of care of the discharge destination after post-acute care in a nursing home. DESIGN: Cohort study. SETTING: Post-acute intermediate care nursing home, 19-bed unit with increased multidisciplinary staff. PARTICIPANTS: Patients ≥70 years in post-acute care (N=900) following an acute admission to the hospital. MEASUREMENTS: The predictive value of nutritional status, as measured by the MNA-SF, on discharge destination was analysed by means of a multinomial logistic regression model with the MNA-SF as the independent variable, discharge destination as the dependent variable and age and living situation as co-variates. The participants were grouped into three categories according to their discharge destination: home, other institution or readmitted to the hospital. RESULTS: A higher score on the MNA-SF significantly predicted a reduced risk of discharge to institution (adjusted OR=0.90 (95% CI=0.84;0.97), p=0.003). CONCLUSION: Nutritional status, as measured by the MNA-SF, predicted discharge destination from an intermediate care nursing home following acute hospitalisation. The findings underscore the value of nutritional assessment as part of overall clinical assessment and care planning prior to discharge. The findings may also imply that interventions to improve nutritional status could increase patients' ability to return home, as opposed to further institutionalisation, after hospitalisation.

Three Different Outcomes in Older Community-dwelling Patients Receiving Intermediate Care in Nursing Home after Acute Hospitalization.

OBJECTIVES: To evaluate the recovery and outcome of older communitydwelling patients admitted to intermediate care (IC) in nursing homes after acute hospitalization, and to compare patients who were able and unable to return directly to their own homes. DESIGN: Prospective, observational, cohort study conducted between June 2011 and 2014. SETTING: A 19- bed IC unit in a nursing home with increased multidisciplinary staffing. PARTICIPANTS: A total of 961 community-dwelling patients, ≥70 years of age, considered to have a rehabilitation potential and no major cognitive impairment or delirium, transferred from internal medicine, cardiac, pulmonary and orthopaedic hospital departments. MEASUREMENTS: Demographic data, clinical information, comprehensive geriatric assessment (CGA), discharge destination and length of stay. Residence status and mortality 1 month, 2 months, 3 months, and 6 months after discharge from the hospital. RESULTS: The trajectory of recovery was divided into 3 groups: 1) Rapid recovery, able to return home after median 14 days in IC (n=785, 82%); 2) Slow recovery, requiring additional transfer to other nursing home after IC, but still able to return home within 2 months (n=106, 11%). 3) Poor recovery, requiring transfer to other nursing home after IC and still in a nursing home or dead at 2 months (n=66, 7%). Significant different clinical characteristics were demonstrated between the patients in the 3 groups. After 6 months, the recovery of patients with rapid or slow recovery was similar, 87% were living at home, compared to only 20% of the patients with poor recovery. In multiple logistic regression analysis, slow or poor recovery was significantly associated with low scores on the Barthel index and orthopaedic admission diagnosis. CONCLUSIONS: Although the majority of patients selected for treatment in the IC unit were able to recover and return home, a group of patients needed extra time, up to 2 months, to recover and another group had a poor chance of recovering and returning home. Different caring pathways for different patient groups may be considered in the PAC setting.

Estimating the glomerular filtration rate using serum cystatin C levels in patients with spinal cord injuries.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: To investigate the relationship between (51)chromium-ethylene-diamine-tetra-acetate ((51)Cr-EDTA) clearance, serum cystatin C (CysC), serum creatinine, creatinine clearance and estimated glomerular filtration rate (eGFR(MDRD), MDRD stands for modification of diet in renal disease) based on the serum creatinine in patients with complete or incomplete spinal cord injury (SCI) and to develop and evaluate a GFR-estimating equation using serum CysC. SETTINGS: Spinal Cord Injury Unit, Viborg Regional Hospital, Viborg, Denmark. METHODS: Ninety-eight men and 47 women with SCI were included in the study. Serum CysC levels were measured by an automated particle-enhanced nephelometric immunoassay, serum and urine creatinine levels were measured by an enzymatic method traceable to the IDMS creatinine reference method, and (51)Cr-EDTA clearance was measured by a multiple plasma sample method. RESULTS: The area under the curves (AUCs) in the non-parametric receiver operating characteristics (ROC) plots for serum CysC were compared with serum creatinine and to eGFR(MDRD) and revealed a significant difference (P-value < 0.05) for all SCI patients. There was no significant difference between the AUC for serum CysC compared with the AUC for creatinine clearance. GFR (ml min(-1) per 1.73 m(2)) can be calculated from serum CysC values (mg l(-1)) using the equation eGFR(CysC) = 212·exp(0.914·CysC). The model accurately predicted the GFR of 88% of patients within ± 30% of the measured GFR, and it was able to predict the GFR of 50% of patients within ± 10% of the measured GFR. CONCLUSION: In patients with SCI, GFR can be estimated independent of age, sex and muscle mass by a newly developed equation based on a single serum CysC value.

Doppler ultrasound compared with strain gauge for measurement of systolic ankle blood pressure.

This study assesses measurement variation in the measurement of ankle systolic blood pressure (ABP) when measured with Doppler ultrasound and with the strain gauge method. Ninety-seven patients were included. ABP was measured with Doppler ultrasound and with the strain gauge method. The methods were compared graphically by scatterplots and analyzed by paired t test, analysis of variance, and Pitman's paired variance ratio test. ABP was measured by strain gauge in all extremities, whereas no Doppler signal was obtainable in 7 limbs (4%). There was no systematic difference in measurements between the means of the two measurements. However, a substantial difference of more than 25 mm Hg was found in 15% of limbs and more than 20 mm Hg in 20%. In the majority of patients, measurements of ABP by Doppler ultrasound and the strain gauge method give similar results, but for a minority the discrepancy is substantial.

The viability of cryopreserved PBPC depends on the DMSO concentration and the concentration of nucleated cells in the graft.

BACKGROUND: DMSO is widely used as a cryoprotectant for PBPC. It is desirable to reduce the amount of DMSO without jeopardizing the quality of the stem cell product. The present study was undertaken to investigate whether recovery and survival of CD34+ cells would be significantly altered when PBPC used for autologous transplantations were cryopreserved with four different DMSO concentrations. METHODS: Apheresis samples of PBPC from 20 consecutive patients were mixed in parallel with 2%, 4%, 5% and 10% DMSO, frozen with identical cell concentrations at a controlled rate, and stored in liquid nitrogen for 6-8 weeks. PBPC samples from 11 consecutive patients were also cryopreserved with two different cell concentrations (150 and 300 x 10(6) nucleated cells/mL) to investigate the effect of increasing the cell concentrations while decreasing the DMSO concentration. The flow cytometric absolute count method, based on ISHAGE guidelines, was used to measure the absolute count of total and viable CD34+ cells in the post-thaw samples. RESULTS: PBPC cryopreserved at 150 x 10(6) cells/mL with 2% DMSO yielded significantly inferior CD34+ cell recovery (P < 0.001) and survival (P < 0.001) compared with cryopreservation with 4% and 5% DMSO. This was also observed when comparing higher cell concentrations. However, a reduced cell survival (P = 0.02) was observed when the nucleated cell concentration was increased from 150 to 300 x 10(6) cells/mL in samples cryopreserved with 5% DMSO. DISCUSSION: We conclude that 5% DMSO may be the optimal dose for cryopreserving PBPC as long as the cells have not been concentrated at much more than 200 x 10(6) nucleated cells/mL.

Large-volume leukapheresis yields more viable CD34+ cells and colony-forming units than normal-volume leukapheresis, especially in patients who mobilize low numbers of CD34+ cells.

BACKGROUND: Large-volume leukapheresis (LVL) differs from normal-volume leukapheresis (NVL) by increased blood flow and altered anticoagulation regimen. LVL is now regarded as a safe procedure for collection of peripheral blood progenitor cells (PBPCs), but it is not known whether the procedure will alter CD34+ cell quality or will be useful for patients who mobilize few CD34+ cells into peripheral blood. STUDY DESIGN AND METHODS: The results from 82 LVL and 125 NVL (4.0-5.3 and 2.7-3.5 times the patients' blood volumes processed, respectively) were retrospectively analyzed in altogether 112 consecutive patients with malignant diseases. RESULTS: The LVL yielded significantly more CD34+ cells (4.2 x 10(6) vs. 3.1 x 10(6)/kg, p = 0.006, all patients; and 1.8 x 10(6) vs. 1.3 x 10(6)/kg, p = 0.004, bad mobilizers) and significantly higher colony-forming units (77 x 10(4) vs. 33 x 10(4)/kg; all patients and 33 x 10(4) vs. 20 x 10(4)/kg, p < 0.001, both groups). Significantly fewer leukapheresis procedures were required to obtain 2 x 10(6) CD34+ cells per kg (one vs. two, p = 0.001, all patients; and two vs. three, p = 0.009, bad mobilizers). No significant differences in CD34+ cell viability and time to hematologic recovery were observed between the patients who received PBPCs harvested by NVL and LVL. CONCLUSION: Although a median platelet loss of 36 percent can be expected, LVL can be recommended as the standard apheresis method for PBPC collections in patients with malignant diseases. LVL is particularly useful in patients who mobilize a low number of CD34+ cells into the peripheral blood.

Autologous transplantation: the viable transplanted CD34+ cell dose measured post-thaw does not predict engraftment kinetics better than the total CD34+ cell dose measured pre-freeze in patients that receive more than 2x10(6) CD34+ cells/kg.

BACKGROUND: The aim of the study was to investigate whether the number of viable CD34+ cells in cryopreserved PBPC autografts is a better predictor of engraftment than the total CD34+ cell number determined before freezing. METHODS: A total of 119 patients was treated with autotransplantation for various malignant disorders during the period 1996-2002. All patients were reinfused with at least 2x10(6)/kg total CD34 cells analyzed before programmed freezing in 10% DMSO. The total CD34 cell number determined before freezing was compared with the number of viable cells determined after cryopreservation for 51 of these patients. The number of viable cells was determined by a flow cytometric analysis including triple staining with anti-CD34, anti-CD45 and the viability marker 7-actinomycin D (7-AAD). RESULTS: Simple linear regression analyses showed that both the total transplanted CD34 cell dose measured before freezing and the viable CD34 cell dose determined after cryopreservation were significantly correlated with neutrophil and platelet engraftment. In a multiple regression model the prediction of engraftment was not improved when the transplanted viable CD34 cell dose was included as a variable in addition to the total CD34 cell dose measured immediately after collection. DISCUSSION: Routine estimation of viable CD34 cells after cryopreservation of PBPC autografts is not necessary as long as the total CD34 cell dose is determined before freezing and the patients are reinfused with at least 2x10(6) cells/kg body weight.

No differences in colony formation of peripheral blood stem cells frozen with 5% or 10% dimethyl sulfoxide.

High-dose chemotherapy with autologous stem cell rescue usually requires cryopreservation of the cells. For several years, 10% dimethyl sulfoxide (DMSO) has been used as the standard cryoprotectant. Because DMSO infusion can lead to toxic clinical complications in a dose-related manner, we wanted to evaluate if reduction to 5% DMSO would be possible. We have compared colony formation in the myeloid, erythropoietic, and megakaryocyte lineages in peripheral blood progenitor cell (PBPC) samples cryopreserved in parallel with 5% and 10% DMSO. Twenty-seven PBPC samples from patients with malignant diseases were investigated after 3 months of cryopreservation in liquid N(2), and samples from 14 of these patients were investigated after 1 year. A significantly higher colony formation was demonstrated for colony-forming units-erythrocyte (CFU-E) and CFU-granulocyte, erythrocyte, macrophage, megakaryocyte (GEMM) both at 3 months and at 1 year in the 5% samples. For CFU-granulocyte-macrophage (GM) and CFU-megakaryocyte (Mk) no significant difference was demonstrated neither at 3 months nor at 1 year in samples frozen with 5% and 10% DMSO. Also, there was a statistically significant correlation between the CFU-total and CFU-Mk-total, indicating that the CFU-total might be used as an evaluation of megakaryocyte progenitors. Viability testing with the Trypan Blue exclusion test showed that cells cryopreserved in 5% DMSO had significantly higher viability than the cells cryopreserved in 10% DMSO. We conclude that 5% DMSO is at least as good for cryopreservation of small-volume PBPC samples as the conventional 10% DMSO, and our results suggest that the possibility of using 5% DMSO for cryopreservation of autologous PBPC grafts should be further investigated in clinical studies.

Long-term risk of second malignancy after treatment of Hodgkin's disease: the influence of treatment, age and follow-up time.

BACKGROUND: To quantify the long-term risk of second cancers (SCs) up to 30 years after primary treatment for Hodgkin's disease (HD) Material and methods In the period 1968 to 1985, an unselected population of 1024 patients started treatment for HD at the Norwegian Radium Hospital (NRH) and were followed for SC from 1969 through 1998 by The Norwegian Cancer Registry. The median age at diagnosis of HD was 40 years, and the median time at follow-up was 14 years. RESULTS: Of 197 SCs, 14 were acute non-lymphocytic leukemia (ANLL), 31 non-Hodgkin's lymphoma (NHL) and 152 solid cancers. The standardized incidence ratio (SIR) was significantly increased for SCs as a group, and for the subgroups ANLL, NHL, lung cancer, breast cancer, stomach cancer and melanoma. ANLL was related to heavy treatment with chemotherapy (CT) and combined CT and radiotherapy (RT), NHL was not treatment related, and solid tumors were related to radiotherapy only or combined RT and CT. The SIR of ANLL and NHL reached a peak between 5 and 10 years after treatment. Solid and non-solid tumors increased with young age at diagnosis of HD and solid tumors increased with follow-up time up to 28 years CONCLUSION: In a long-term follow-up study of HD patients of all ages, the SIR of solid tumors was high in patients treated at young age and decreased with increasing age. Most solid tumors had started within or at the edge of the irradiated field, and SIR of solid tumors increased even 20-30 years after diagnosis.

Serum cystatin C as a marker of the renal function in patients with spinal cord injury.

OBJECTIVE: To investigate the relationship between serum cystatin C, serum creatinine, and (51)Cr-EDTA-clearance in patients with spinal cord injury. SETTING: The Spinal Cord Unit, Viborg-Kjellerup County Hospital. METHODS: Twenty-four men and seven women aged 20.3 to 68.0 years with motor complete spinal cord injury (ASIA A or B) were included. Serum cystatin C was measured by an automated particle-enhanced nephelometric immunoassay (Dade Behring), serum creatinine by an enzymatic method (Vitros 950), and (51)Cr-EDTA-clearance by a multiple plasma sample method. RESULTS: A linear relationship was found between (51)Cr-EDTA-clearance and the reciprocal values of cystatin C and creatinine. The correlation coefficient between (51)Cr-EDTA-clearance and 1/cystatin C was 0.72 compared to the correlation coefficient between (51)Cr-EDTA-clearance and 1/creatinine being 0.26. Comparison of the area under the curves in the non-parametric receiver operating characteristics (ROC) plots for serum cystatin C (area under the curve (AUC)=0.912; SE=0.065), and serum creatinine (AUC=0.507; SE=0.115) revealed significant differences (P-values=0.0005). CONCLUSION: In patients with spinal cord injury serum cystatin C is a better marker of the renal function compared to serum creatinine.

Flow cytometric measurement of apoptosis and necrosis in cryopreserved PBPC concentrates from patients with malignant diseases.

The number of viable precursor cells actually reinfused into patients after high-dose chemotherapy is one of the most clinically important variables determining graft success or failure. A modified, previously described flow cytometric method based on annexin V staining was therefore applied to assess the degree of apoptosis and necrosis in cryopreserved PBPC concentrates from patients with malignant diseases. Twenty-two samples of unmanipulated cryopreserved PBPC concentrates were analyzed by flow cytometry. The samples were triple-stained with anti-CD34 PE, annexin V-FITC and actinomycin D, which enabled the separation of viable, early apoptotic and late apoptotic/necrotic CD34(+) precursor cells. Apotosis and necrosis were also measured in the total cell population of the concentrates. Eighty-one percent (range 49-97) of the CD34(+) cells were viable, while 7% (range 1-15) were early apoptotic and 12% (range 2-36) were late apoptotic/necrotic after freeze/thaw. There was no difference in apoptosis and necrosis in CD34(+) cells harvested from mildly pretreated patients with multiple myeloma and heavily pre-treated patients with non-Hodgkin's lymphoma. Apoptosis and necrosis were higher in the total mature cell population of the concentrates. Thirty-two percent (range 7-69) of the cells were apoptotic and 33% (range 12-60) were necrotic. We conclude that flow cytometric analysis of annexinV/actinomycin D binding in PBPC concentrates is a simple technique that can give additional information of the viability status of the cells post thaw. The present study confirms the relative robustness of human CD34(+) precursor cells concerning the freeze/thaw procedure, which are carried out in daily clinical practice.

Peripheral blood progenitor cell grafts contain high levels of platelet-secreted mediators.

BACKGROUND: The cytokine network in peripheral blood progenitor cell (PBPC) grafts may affect hematopoietic reconstitution or the risk of postransplant relapse of malignant disorders through effects on normal progenitor cells or contaminating malignant cells. Whether thrombopoietin (TPO), SCF, and platelet-secreted mediators are parts of this network was investigated. STUDY DESIGN AND METHODS: Peripheral blood and PBPC plasma samples were collected consecutively from patients with malignant disorders who underwent PBPC harvest. Blood samples were collected immediately before and after apheresis. Patients underwent mobilization by chemotherapy plus G-CSF, except for one patient who received only G-CSF. Plasma levels were also determined for healthy controls. RESULTS: PBPC grafts had greater levels of platelet-secreted platelet factor 4 (PF4), beta-thromboglobulin, and platelet-derived growth factor isoform AB, as compared with venous levels in patients and controls. Although platelet and PF4 levels in autografts were significantly correlated, the graft:blood ratio was higher for PF4 than for platelets. In both the patients' blood and the autografts, TPO levels were increased from the levels in normal controls. Blood and graft levels of SCF were within the normal range. CONCLUSION: The cytokine network of PBPC autografts includes increased levels of TPO and several platelet-derived mediators.

High arterial compliance in cirrhosis is related to low adrenaline and elevated circulating calcitonin gene related peptide but not to activated vasoconstrictor systems.

BACKGROUND AND AIMS: Static and dynamic functions of the wall of large arteries are largely unknown in cirrhosis in vivo. The present study was undertaken to determine arterial compliance (COMP(art)) in relation to vasodilator and vasoconstrictor systems in patients with cirrhosis. In addition, vasoactivity was manipulated by inhalation of oxygen. STUDY POPULATION AND METHODS: In 20 patients with alcoholic cirrhosis and 12 controls we determined COMP(art) (stroke volume relative to pulse pressure), cardiac output, plasma volume, systemic vascular resistance, central circulation time, plasma catecholamines, renin activity, endothelin-1, and calcitonin gene related peptide (CGRP) at baseline and during oxygen inhalation. RESULTS: COMP(art) was significantly increased in cirrhotic patients compared with controls (1.32 v 1.06 ml/mm Hg; p< 0.05) and inversely related to plasma adrenaline levels (r=-0.53; p<0.02) but positively related to circulating levels of CGRP (r=0.58; p<0.01). No significant relation was found for plasma noradrenaline, renin activity, or endothelin-1. COMP(art) was positively related to plasma volume (r=0.50; p<0.02) and inversely to systemic vascular resistance (r=-0.69; p<0.001) and central circulation time (r=-0.49; p<0.02). During oxygen inhalation, COMP(art) decreased (-13%; p<0.005) and systemic vascular resistance increased (+10%; p<0.001) towards normal values without significant changes in mean arterial pressure. Plasma adrenaline (-16%; p<0.01) decreased and the relation to COMP(art) disappeared. The relation of COMP(art) to CGRP and circulatory variables remained unchanged. CONCLUSION: Elevated arterial compliance in cirrhosis is related to low adrenaline, high CGRP, and systemic hyperdynamics but not to indicators of the activated vasoconstrictor systems (noradrenaline, renin, endothelin-1). Thus the altered static and dynamic characteristics of the wall of large arteries are intimately associated with circulatory and vasodilatory derangement in cirrhosis but biomanipulation indicates that the changes are, at least in part, reversible during isobaric conditions.

Autologous stem cell transplantation as post-remission therapy in adult acute myelogenous leukemia: does platelet contamination of peripheral blood mobilized stem cell grafts influence the risk of leukemia relapse?

Conventional chemotherapy of acute myelogenous leukemia (AML) results in an overall long-term disease-free survival of less than 50%, but for selected subsets of younger patients the prognosis can be improved by allogeneic stem cell transplantation. The use of autologous stem cell transplantation is now investigated as an alternative to allotransplantation due to its lower risk of serious complications. However, autotransplantation is associated with a relatively high risk of post-transplant AML relapse that can be derived from contaminating leukemia cells in the autograft. Peripheral blood mobilized stem cell (PBSC) grafts usually contain a higher number of platelets. The degree of platelet contamination is determined by the peripheral blood platelet count at the time of harvesting, and the platelets become activated and release soluble mediators during the ex vivo handling of PBSC grafts. Many of these platelet-derived mediators can bind to specific receptors expressed by AML blasts, and the platelet contamination may then alter AML blast survival and thereby influence the risk of post-transplant leukemia relapse. Therefore, we conclude that the platelet contamination of autologous stem cell grafts is possibly of clinical importance, but the effect of this nonstandardized parameter is difficult to predict in individual patients because the number of graft-contaminating platelets, the degree of platelet activation, and the effects of platelet-derived mediators on AML blasts differ between patients.

[High dose chemotherapy with autologous stem cell support in cancer patients]. / Høydosebehandling med autolog stamcellestøtte hos kreftpasienter.

INTRODUCTION: In 1996 it was decided that high-dose chemotherapy with peripheral stem cell support should be offered by all five university hospitals in Norway. MATERIAL AND METHODS: We report on the first 49 patients from the western part of Norway treated with this modality at Haukeland University Hospital in the 1996-98 period. RESULTS: All patients had a total of > 2-10(6) CD34 positive cells/kg collected before high-dose chemotherapy. To achieve this critical stem cell dose, five patients had to have three or more stem cell collections; four of them had to be mobilised several times. Poor stem cell mobilisation was mostly marked in patients with soft tissue sarcoma and testicular cancer, but was also observed in a few heavily pre-treated patients with non-Hodgkins lymphoma. With the exception of one lymphoma patient who developed a rapid bone marrow relapse, all patients had satisfactory sign of bone marrow regeneration after reinfusion of the stem cells. This also applied to the poor mobilisors. No treatment-related deaths have occurred. Four to 38 months after high-dose therapy, 33% of patients with multiple myeloma and 52% of patients with malignant lymphoma were alive and in complete remission. Three of the four patients with soft tissue sarcoma relapsed 3-7 months after high-dose chemotherapy.

Percutaneous transluminal angioplasty in selected patients with severe carotid artery stenoses: the results of a consecutive series of 24 patients.

OBJECTIVES: To assess clinically and with duplex scanning the results of percutaneous transluminal angioplasty in a subgroup of patients with carotid artery stenosis. DESIGN: A retrospective study. MATERIALS: Twenty-four patients with focal hemispheric neurological symptoms from a concentric, smooth carotid stenosis more than 70% treated with balloon dilatation. Control investigations were performed with duplex scanning. RESULTS: Angiography after PTA revealed no residual stenosis in 15 patients (62%), a stenosis of less than 50 was seen in seven patients (30%) and PTA was ineffective in two patients (8%). Three patients (13%) had transient ischaemic attacks during the procedure but none had strokes. One patient experienced short lasting paraesthesia of the arm a few hours after the PTA procedure. After a follow-up of a mean of 11 months (1-38) no recurrent symptoms had occurred. Clinical success was thus achieved in 22 of 24 patients (92%). At duplex scanning, 16 (66%) patients had no stenosis, six patients (30%) had a stenosis of 70%, one patient (4%) a stenosis of 80%, and one patient had an occluded carotid artery. CONCLUSION: Our results indicate that PTA in a selected group of patients with carotid artery stenosis is safe and the interim, long-term results are promising. The procedure must be evaluated in a randomised prospective study against surgical treatment.

Insulin-like growth factor-1 (IGF-1) has a costimulatory effect on proliferation of committed progenitors derived from human umbilical cord CD34+ cells.

The effects of insulin-like growth factor-1 (IGF-1) on highly enriched human umbilical cord CD34+ cells were investigated in vitro. CD34+ cells were cultured in serum-free medium containing stem cell factor (SCF), GM-CSF, and interleukin-3 (IL-3). Culture of CD34+ cells for one week in the presence of these cytokines resulted in a dose-dependent increase in total cell number. Addition of G-CSF together with SCF+IL-3+GM-CSF increased the proliferation of myelopoietic cells as determined by the number of cells expressing the myelomonocytic marker CD64 and the granulocytic marker CD15 without significantly altering the number of CD34+ cells in the cultures. In the presence of G-CSF, IGF-1 induced a dose-dependent increase in the total cell number and a moderate but significant increase in the percentages of CD15+, CD64+ cells with sustained CD34+ cell proliferation. We conclude that IGF-1 can enhance the in vitro proliferation of committed progenitor cells derived from umbilical cord CD34+ cells.

Acute cardiovascular effect of 1,25-dihydroxycholecalciferol in essential hypertension.

A role for vitamin D in the pathophysiology of essential hypertension has frequently been suggested, but acute direct effects on blood pressure, cardiac output, renal hemodynamics, or hormones have not previously been demonstrated. The rapid effects of 1,25-dihydroxycholecalciferol (1,25-D) were assessed over 120 min after a bolus injection (0.02 microg/kg body weight) in eight men with essential hypertension and in nine healthy men. A placebo group of 10 healthy men was also included. Ionized calcium was monitored closely during the study, and was kept constant with a clamping technique. In the hypertensive patients, a transient increase in blood pressure and a reciprocal fall in cardiac output measured by a CO2 rebreathing technique (-15%, P < .05) were observed after 1,25-D injection. In the control group, both blood pressure and cardiac output remained unchanged. The glomerular filtration rate, effective renal plasma flow, and urinary sodium and water excretions were unchanged in both groups. Plasma levels of atrial natriuretic peptide at baseline were higher in the hypertensive patients than in the control subjects (P < .02); plasma levels of renin, aldosterone, norepinephrine, endothelin, and parathyroid hormone(1-84) were similar in the two groups. None of these hormones was affected during the observation time after the injection of 1,25-D. In conclusion, acute administration of 1,25-D caused a fast and likely nongenomic-mediated decrease in cardiac output in patients with essential hypertension, which together with a transient BP increase implies a 1,25-D-induced increase in total peripheral resistance. These data suggest an enhanced cardiovascular responsiveness to 1,25-D in hypertensive compared to healthy normotensive subjects.

Variation in cell yield and proliferative activity of positive selected human CD34+ bone marrow cells along the circadian time scale.

Variations in cell yield and proliferative activity of human bone marrow (BM) progenitor cells were determined with flow cytometry along the 24-h (circadian) time scale. Equal volumes of BM were aspirated every 5 h, altogether 5 times in 5 healthy men. An average 6-fold higher yield of positive selected CD34+ cells occurred in each subject when BM was aspirated during the daytime and late afternoon, while a lower yield occurred during the night. Using all CD34+ cell yield data normalized to percentage of mean, a significant time-effect was found by ANOVA (p = 0.02) and a significant circadian rhythm was detected by the least-squares fit of a 24 h cosine (p = 0.02). The 95% confidence limits of the acrophase (time of highest values) were computed to be at midday between 10:24 and 14:48 h. A highly significant correlation (p = 0.001) was found between proliferation of positive selected CD34+ cells and the more mature myeloid precursor cells from the same BM aspirates, suggesting a common temporal pattern along the circadian time scale. However, no correlation was demonstrated between proliferation and cell yield of CD34+ selected cells, suggesting that mechanisms other than variation in proliferation may cause the circadian rhythm in stem cell yield. These circadian variations in stem cell yield and proliferation suggest that proper timing within 24 h may potentially be important regarding outcome from progenitor cell harvesting and treatment with haematopoietic growth factors.