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Biomedical subjects

J S Miller

Publications and source records attributed to J S Miller.

At least 73 records · Page 4Linked to original sources
PubMed1998

Choice of mitral prosthesis in the elderly. An analysis of actual outcome.

BACKGROUND: In younger patients requiring mitral valve replacement (MVR), mechanical prostheses (MPs) have been reported to give better freedom from all valve-related complications (VRCs) because of the high incidence of late valve degeneration (VD) associated with bioprostheses (BPs). In older patients, however, the risk of VD may be reduced because of the large competing risk of noncardiac death (NCD). Previous studies on VD in the elderly have used actuarial analysis, which overestimates the risk of VD in this population because it assumes that dead patients are still at risk. In contrast, cumulative incidence (actual) analysis acknowledges that patients who die have no risk of VD. This study compares the results of both "actual" and "actuarial" analyses of the freedom from VD in elderly patients undergoing MVR. METHODS AND RESULTS: From June 1976 through January 1996, 504 patients > or = 70 years of age underwent MVR at our institution. Isolated mitral operations were performed in 159 patients, and 169 had concomitant CABG. Hospital mortality was 59 of 374 (15.9%) for tissue prosthesis versus 24 of 130 (18.5%) for mechanical prosthesis (P = NS). For tissue versus mechanical prosthesis, 10-year freedom from noncardiac death was 75.0% versus 67.6% (P = NS); 10-year actuarial freedom from valve degeneration was 79.8% versus 93.4% (P = NS); 10-year actual freedom from valve degeneration was 92.6% versus 95.4% (P = NS); and 10-year actual freedom from all VRCs was 84.4% versus 92.3% (P = NS). CONCLUSIONS: In elderly patients undergoing MVR, actuarial analysis overestimates the 10-year risk of VD compared with actual analysis (20.2% versus 7.4% for BP, 6.6% versus 4.6% for MP). In these patients, the actual freedoms from VD and all VRCs do not differ significantly between BP and MP. Thus, in this age group, the necessity for anticoagulation or its avoidance may be the predominant factor in choosing a replacement mitral valve.

Actuarial Analysis↗
PubMed1998

Comparative analysis of autografting in chronic myelogenous leukemia: effects of priming regimen and marrow or blood origin of stem cells.

The aims of this study were (1) to evaluate the effect of intermediate (cyclophosphamide alone) or intensive (mitoxantrone, cytosine arabinoside, cyclophosphamide) priming on the cytogenetic response in mobilized bone marrow (BM) or peripheral blood (PB) progenitors in patients with chronic myelogenous leukemia (CML), (2) to determine the incidence of cytogenetic remissions after mobilized progenitor transplantation in CML, and (3) to determine the effect of in vivo priming on the ability to select Philadelphia chromosome-negative (Ph-negative) CD34(+)HLA-DR- cells from mobilized BM or PB in quantities sufficient for transplantation. Between February 1994 and March 1997, 44 patients were enrolled in three sequential protocols. Although the duration of neutropenia after only cyclophosphamide mobilization was shorter, clinical morbidity for the intermediate and intensive priming protocols was similar. Cytogenetic responses in mobilized PB progenitors were similar after mobilization with either intermediate or intensive chemotherapy. The degree of Ph negativity in the mobilized product correlated with disease stage at the time of mobilization (early chronic phase [ECP] > late CP > accelerated phase). Cytogenetic responses after transplantation with mobilized progenitors obtained after the different regimens were similar. The cytogenetic status of the graft predicted the cytogenetic status of marrow obtained 3 weeks after transplantation whereas cytogenetic responses 3, 6, and 12 months after transplantation correlated with the number of BCR/ABL-negative CD34(+)HLA-DR- cells, but not the number of Ph-negative metaphases in the graft. In patients with ECP CML, mobilized PB collections yielded significantly more CD34(+)HLA-DR- cells than from steady state or mobilized BM. CD34(+)HLA-DR- cells were Ph negative and polyclonal (X-chromosome inactivation) in the majority of ECP CML patients, before and after mobilization and irrespective of the mobilization regimen. Because infusion of large numbers of Ph-negative CD34(+)HLA-DR- cells predicted superior outcome after transplantation, approaches in which CD34(+)HLA-DR- cells are selected from mobilized PB may result in longer lasting and clinically significant cytogenetic responses after transplantation.

Adult↗
PubMed1998

Ex vivo culture of CD34+/Lin-/DR- cells in stroma-derived soluble factors, interleukin-3, and macrophage inflammatory protein-1alpha maintains not only myeloid but also lymphoid progenitors in a novel switch culture assay.

We have demonstrated that long-term culture initiating cells (LTC-IC) are maintained in a stroma noncontact (SNC) culture where progenitors are separated from stroma by a microporous membrane and LTC-IC can proliferate if the culture is supplemented with interleukin-3 (IL-3) and macrophage inflammatory protein-1alpha (MIP-1alpha). We hypothesize that the same conditions, which result in LTC-IC proliferation, may also maintain lymphoid progenitors. Natural killer (NK) cells are of lymphoid lineage and a stromal-based culture can induce CD34+/Lin-/DR- cells to differentiate along the NK cell lineage. We developed a three-step switch culture assay that was required to demonstrate the persistence of NK progenitors in CD34+/Lin-/DR- cells assayed in SNC cultures supplemented with IL-3 and MIP-1alpha. When CD34+/Lin-/DR- progeny from the SNC culture were plated sequentially into "NK cell progenitor switch" conditions (contact with stromal ligands, hydrocortisone-containing long-term culture medium, IL-2, IL-7, and stem cell factor [SCF]) followed by "NK cell differentiation" conditions (contact with stromal ligands, human serum, no hydrocortisone, and IL-2), significant numbers of CD56+/CD3- NK resulted, which exhibited cytotoxic activity against K562 targets. All steps are required because a switch from SNC cultures with IL-3 and MIP-1alpha directly to "NK cell differentiation" conditions failed to yield NK cells suggesting that critical step(s) in lymphoid commitment were missing. Additional experiments showed that CD34+/CD33- cells present after SNC cultures with IL-3 and MIP-1alpha, which contained up to 30% LTC-IC, are capable of NK outgrowth using the three-step switch culture. Limiting dilution analysis from these experiments showed a cloning frequency within the cultured CD34+/CD33- population similar to fresh sorted CD34+/Lin-/DR- cells. However, after addition of FLT-3 ligand, the frequency of primitive progenitors able to develop along the NK lineage increased 10-fold. In conclusion, culture of primitive adult marrow progenitors ex vivo in stroma-derived soluble factors, MIP-1alpha, and IL-3 maintains both very primitive myeloid (LTC-IC) and lymphoid (NK) progenitors and suggests that these conditions may support expansion of human hematopoietic stem cells. Addition of FLT-3 ligand to IL-2, IL-7 SCF, and stromal factors are important in early stages of NK development.

Adult↗
PubMed1998

FLT-3 ligand and marrow stroma-derived factors promote CD3gamma, CD3delta, CD3zeta, and RAG-2 gene expression in primary human CD34+LIN-DR- marrow progenitors.

We hypothesize that early lymphoid commitment from primitive hematopoietic marrow progenitors is governed by signals from the marrow microenvironment leading to sequential induction of lineage-specific genes. Using expression of lymphoid genes as markers of differentiation, we characterize a highly purified population (>99.8% by double sorting) of primary human CD34+Lin-DR- progenitors. This population was then used to evaluate the effects of supplemental cytokines (interleukin-2 [IL-2], IL-3, IL-7, c-kit ligand), FLT-3 ligand (FL), and stroma-derived factors on lymphoid differentiation in vitro. CD3, RAG-1, Ikaros, CD10, and TdT transcripts were detected in the starting CD34+Lin-DR- population. By contrast, CD3gamma, CD3delta, CD3zeta, and RAG-2 transcripts were not present in any samples tested. The presence of supplemental cytokines alone at culture initiation permitted stimulation of the expression of CD3zeta, but not of CD3gamma or CD3delta. However, when FL and stroma-derived factors were added to cytokines, CD3 gene expression was induced in all samples. The predominant CD3 transcripts induced by optimal culture conditions were alternatively spliced isoforms lacking transmembrane sequences (CD3delta and CD3gamma) and portions of the intracellular and extracellular domains (CD3gamma). The combination of cytokines, FL, and stromal factors also provided a potent stimulus for RAG-2 gene expression. These findings show that FL in combination with stroma-derived factors provide important signals to promote early events required for lymphoid differentiation.

Alternative Splicing↗
PubMed1998

Early results of posterior leaflet folding plasty for mitral valve reconstruction.

BACKGROUND: Standard reconstruction for posterior mitral leaflet (PML) disease is quadrangular resection and annular plication; when the PML is excessively high, a sliding plasty is used. We have developed an alternative technique, a posterior leaflet folding plasty. It is performed by folding down the cut vertical edges of the PML. The central height of the PML is reduced, leaflet coaptation is moved posteriorly, and annular plication is unnecessary. METHODS: From March 1995 to August 1996, 26 (17.9%) of 145 patients undergoing mitral reconstruction had a posterior leaflet folding plasty. Concomitant procedures included anterior leaflet resection or resuspension and myotomy and myectomy. In 3 patients, the PML resection extended to a commissure. RESULTS: There was one death and no reoperations. The mean New York Heart Association class was improved from 2.4 preoperatively to 1.4. There was no major postoperative mitral insufficiency in the 26 patients. Systolic anterior motion was transiently seen in 1 patient in whom left ventricular outflow tract obstruction was present preoperatively. CONCLUSIONS: The data demonstrate the safety and short-term efficacy of posterior leaflet folding plasty. This technique may help avoid systolic anterior motion after reconstruction of the PML.

Adult↗
PubMed1998

Valve repair versus replacement for mitral insufficiency: when is a mechanical valve still indicated?

OBJECTIVES: Although many advantages of mitral valve reconstruction have been demonstrated, whether specific subgroups of patients exist in whom mechanical valve replacement offers advantages over mitral reconstruction remains undetermined. METHODS: This study examined the late results of mitral valve surgery in patients with mitral insufficiency who received either a St. Jude Medical valve (n = 514) or a mitral valve reconstruction with ring annuloplasty (n = 725) between 1980 and 1996. RESULTS: Overall operative mortality was 7.2% in the patients receiving a St. Jude Medical mitral valve and 5.4% in those undergoing mitral valve reconstruction (no significant difference); isolated mortality was 2.5% in the St. Jude Medical group and 2.2% in the valve reconstruction group (no significant difference). The follow-up interval was more than 5 years for 340 patients with a mean of 39.8 months (98.5% complete). Overall 8-year freedom from late cardiac death, reoperation, and all valve-related complications was 72.8% for the St. Jude Medical group and 64.8% for valve reconstruction group (no significant difference). For patients with isolated, nonrheumatic mitral valve disease, 8-year freedom from late cardiac death and reoperation was better in the mitral valve reconstruction group (88.3%) than in the St. Jude Medical valve group (86.0%; p = 0.05). Furthermore, Cox proportional hazards regression revealed that mitral valve reconstruction was independently associated with a lesser incidence of late cardiac death (p = 0.04), irrespective of preoperative New York Heart Association class. However, the St. Jude Medical valve offered better 8-year freedom from late cardiac death, reoperation, and all valve-related complications than did mitral valve reconstruction in patients with multiple valve disease (77.0% vs 45.3%; p < 0.01). CONCLUSIONS: Therefore, mitral valve reconstruction appears to be the procedure of choice for isolated, nonrheumatic disease, whereas insertion of a St. Jude Medical valve should be preferred for patients with multiple valve disease.

Cardiac Surgical Procedures↗
PubMed1998

Minimally invasive port-access coronary artery bypass grafting with early angiographic follow-up: initial clinical experience.

OBJECTIVE: New techniques for minimally invasive coronary artery bypass grafting have recently emerged. The purpose of this study was to determine the safety and efficacy of Port-Access (Heartport, Inc., Redwood City, Calif.) coronary revascularization and to evaluate with angiography the early graft patency rate with this new approach. METHODS: From October 1996 to May 1997, 31 patients underwent Port-Access coronary artery bypass grafting with an anterior minithoracotomy and endovascular-occlusion cardiopulmonary bypass. There were 26 men and 5 women with a mean age of 62 years (range 42 to 82 years). Fifteen patients underwent single bypass; 12 patients underwent double bypass, and 4 patients underwent triple bypass. Bypass conduits included the left internal thoracic artery (n = 30), right internal thoracic artery (n = 2), radial artery (n = 10), and saphenous vein (n = 6). Three sequential grafts were used. Angiographic studies of the bypass grafts were performed in 27 of 31 patients (87%). RESULTS: There were no deaths, neurologic deficits, myocardial infarctions, or aortic dissections. Conversion to sternotomy was not required in any case. There were two reoperations for bleeding, one reoperation for tamponade, and one reoperation for pulmonary embolus. Postoperative angiography revealed anastomotic patency of the left internal thoracic artery to left anterior descending artery in 26 of 26 grafts (100%) with overall anastomotic patency in 43 of 44 grafts (97.7%). CONCLUSION: These results demonstrate that Port-Access coronary artery bypass can be performed accurately and safely with acceptable morbidity. This approach allows for multivessel revascularization on an arrested, protected heart with excellent anastomotic precision and reproducible early graft patency.

Adult↗
PubMed1998

Innovative therapy for chronic myelogenous leukemia.

Innovative therapies for chronic myelogenous leukemia (CML) have focused mainly on combining autologous transplantation with another modality of therapy for purging of the graft or treatment of the patient after transplant. Of the three categories of innovative therapies, two are based on studies that demonstrate the bcr/abl gene rearrangement in the pathogenesis of CML, whereas the third is based on the observation that allogeneic disparity is important to maintain remissions in CML. The rationale and data supporting these innovative approaches are reviewed in this article and future strategies are discussed.

Bone Marrow Purging↗
PubMed1998

Three new ellagic acid derivatives from the bark of Eschweilera coriacea from the Suriname rainforest.

Bioassay-guided fractionation of Eschweilera coriacea collected in the lowland wet forest of Suriname yielded the new but only weakly active ellagic acid derivative eschweilenol A (1) and the two new but inactive ellagic acid derivatives eschweilenol B (2) and eschweilenol C (3). The four known compounds, sucrose, ellagic acid, 3-O-galloylepigallocatechin, and epigallocatechin, were also isolated. The structures of the three new compounds were determined by spectrometric methods, primarily from the HMQC, HMBC, NOESY, and ROESY NMR techniques, and chemical methods, including methylation and triethylsilylation. The location of a hydroxyl group in one ellagic acid derivative was determined by a new technique involving an NOE correlation of the protons of a triethylsilyl derivative with a proton on a neighboring aromatic ring.

Antifungal Agents↗
PubMed1998

Graft-versus-leukemia is sufficient to induce remission in juvenile myelomonocytic leukemia.

It has been unclear whether a graft-versus-leukemia (GVL) effect assists in the control of juvenile myelomonocytic leukemia (JMML) following allogeneic bone marrow transplant. We describe a patient with JMML who relapsed early after an unrelated donor transplant, and following withdrawal of immunosuppression developed graft-versus-host disease (GVHD). Associated with GVHD the proportion of donor cells measured by variable nucleotide tandem repeat (VNTR) analysis increased, and peripheral blasts and cutaneous disease were eliminated. These findings strongly suggest that GVL has a role in the control of JMML.

Bone Marrow Transplantation↗
PubMed1998

Activated peripheral blood mononuclear cells from patients receiving subcutaneous interleukin-2 following autologous stem cell transplantation prolong survival of SCID mice bearing human lymphoma.

Interleukin-2 (IL-2) after autologous stem cell transplantation (SCT) is being explored as a way of reducing relapse. To determine the immunostimulating effect of low-dose subcutaneous IL-2 following SCT, the in vitro and in vivo activity of patient peripheral blood mononuclear cells (PBMNC) was studied. A predominantly natural killer (NK) lymphocytosis was induced and sustained throughout most of the IL-2 treatment period. The in vivo primed PBMNC had enhanced lytic activity against a variety of tumor targets. The in vitro cytotoxicity of in vivo IL-2-primed PBMNC could be increased further by overnight incubation in 1000 U/ml IL-2. The SU-DHL-4 B cell lymphoma xenotransplantation model was used as an in vivo system for testing the efficacy of cellular therapy. PBMNC obtained by apheresis from autografted patients that had received post-transplant IL-2 for 35-42 days were infused i.v. into SU-DHL-4 bearing C.B-17 severe combined immunodeficient (SCID) mice. Control mice died of disseminated lymphoma at a median of 35.2 days, while murine recipients of in vivo activated human PBMNC cells from IL-2-treated SCT patients survived significantly longer (58.2 days). The in vivo effect of human PBMNC on survival of tumor-bearing mice correlated well with their in vitro cytolytic activity as assessed by 51Cr release assays, indicating that the SCID SU-DHL-4 lymphoma model can be utilized reliably to test the efficacy of cellular therapy in vivo.

Administration, Cutaneous↗
PubMed1998

Ruptured aortic pseudoaneurysm 28 years after gunshot wound: case report and review of the literature.

Penetrating injuries to the abdominal aorta most often result in rapid exsanguination and death. Immediate surgical intervention may result in control of hemorrhage and survival of the patient. Rarely, hemorrhage after aortic injury may be contained by surrounding tissues, resulting in pseudoaneurysm formation. Traumatic pseudoaneurysms may rupture at any time, and this is usually a fatal event. A 47-year-old man recently presented with a supraceliac abdominal aortic pseudoaneurysm that ruptured into the right chest 28 years after a gunshot wound to the back. This report describes the pathophysiology, diagnosis, and treatment of traumatic pseudoaneurysms of the abdominal aorta and includes a review of the literature. This is a case in which a traumatic pseudoaneurysm of the abdominal aorta was successfully repaired by surgery after rupture into the thorax and is the first such case to be reported in the literature.

Aneurysm, False↗
PubMed1998

The changing face of long-term care.

When it comes to long-term care insurance, most people think of elderly clients. Providers who understand the benefits of this type of insurance can suggest this option to individuals to ensure that they can remain at home.

Aged↗
PubMed1998

Aging in the Amish community.

The experience of aging in The Old Order Amish Community, of Lancaster County, Pennsylvania, is explored from the viewpoint of the elderly. Through personal interviews with elderly Amish and others knowledgeable about the community, the influence of religious beliefs and practices as the core of their lifestyle becomes evident. The entire community, not just family members, cares for the elders with respect and loving care, generally without recourse to any external resources from the non-Amish.

Adolescent↗
PubMed1997

Natural killer (NK) cells are functionally abnormal and NK cell progenitors are diminished in granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cell collections.

Granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood progenitor cell (PBPC) collections are increasingly emerging as the graft of choice in many centers for autologous transplantation, and with increasing frequency for allogeneic transplantation. However, the role of myeloid cytokines in lymphoid function, lymphoid progenitors, and immune-mediated antitumor responses is not known. We studied PBPC collections from normal donors mobilized with G-CSF (10 microg/kg). CD56+/CD3- natural killer (NK) cells sorted from PBPC products exhibited a diminished ability to kill tumor targets, were less responsive in acquiring increased cytolysis with interleukin-2 (IL-2), and proliferated less than NK cells from normal unprimed peripheral blood. This abnormality was not explained by a change in phenotype of NK cells normally circulating in the blood after G-CSF administration. We could not demonstrate any direct suppressive effect on normal unprimed NK cell proliferation or cytotoxicity by culture with pharmacologic concentrations of G-CSF. We next evaluated the effects of G-CSF on CD34+ NK cell progenitors. CD34+/CD2+, CD34+/CD7+, and CD34+/CD10+ progenitors were markedly diminished in G-CSF-mobilized PBPC products. CD34+ cells cultured in limiting dilution assays showed a sixfold decrease in NK cell progenitors when derived from G-CSF-mobilized CD34+ PBPCs compared with CD34+ cells derived from unprimed marrow. The finding of decreased NK cell function, inhibited proliferation, and diminished cloning frequency after treatment with G-CSF could be mimicked in vitro by culture of primitive marrow progenitors (CD34+, lineage-negative, HLA-DR-) on stromal layers in the presence of exogenous G-CSF. The findings presented here show that G-CSF administration to normal donors decreases NK cell function and the relative frequency of NK cell progenitors within the CD34+ progenitor population. Overcoming this diminished lymphoid capacity may be important to facilitate early posttransplant immunotherapy. Our in vitro model will be used in future studies to determine the mechanism of the G-CSF-induced suppression of NK cell progenitors, which may occur early in the differentiation process.

Antigens, CD34↗
PubMed1997

Postoperative pain control after lumbar spine fusion. Patient-controlled analgesia versus continuous epidural analgesia.

STUDY DESIGN: A prospective, randomized, double-blind clinical trial. OBJECTIVE: To compare the efficacy of postoperative continuous epidural analgesia versus patient-controlled analgesia in patients undergoing lumbar fusion. SUMMARY OF BACKGROUND DATA: Controversy remains regarding the optimal strategy for postoperative pain control. METHODS: Fifty-four patients were divided into two treatment groups. There was no difference between the groups with respect to age, levels fused, estimated blood loss, and use of spinal instrumentation. Patient-controlled analgesia or epidural analgesia was administered in a double-blind manner for a 3-day postoperative course. Each patient received both an epidural and a patient-controlled analgesia delivery system; 26 received the epidural active agent and 28 received patient-controlled analgesia. Postoperative time to liquids and solid food, ambulation, length of stay, and side effects was recorded. Pain was evaluated by a visual analog scale on postoperative days 1, 2, and 3. RESULTS: Results showed no difference between the groups with reference to diet, ambulation, length of stay, and visual analog scale scores. Minor side effects occurred in 71% of patients in both groups. No major complications occurred. Epidural catheter dislodgment occurred in 11% of patients. The total cost for epidural analgesia was approximately $550 more than that for patient-controlled analgesia for a 3-day postoperative course. CONCLUSIONS: These data suggest that there is no clinical advantage of epidural opiate/local anesthetic analgesia over systemic opiate by patient-controlled analgesia for spinal fusion patients. However, possible technical limitations (namely, the low dosage of bupivacaine and placement of the catheter tip) may have prevented adequate delivery of anesthetic to the involved segments. Although the incidence of side effects is similar, cost factors and a high incidence of epidural catheter dislodgment favor use of patient-controlled analgesia.

Adult↗