Botulinum toxin and conservative treatment strategies in people with cervical dystonia: an online survey.

Isolated cervical dystonia is a focal, idiopathic dystonia affecting the neck muscles. Treatment usually consists of botulinum neurotoxin (BoNT) injections into the dystonic muscles. Our aim is to investigate the use of BoNT treatment and conservative treatments by people living with cervical dystonia. An online survey in English was conducted between June and August 2022. Participants were eligible to participate if they were living with cervical dystonia, were over 18 years old and could read and understand English. The survey consisted of demographic questions, characteristics of dystonia, questions relating to BoNT use and the perceived utility of conservative treatments. The data were analysed descriptively, and open-ended questions were grouped into similar topics represented by direct quotes. We received 128 responses from people with cervical dystonia, with an average age of 59 years and 77% women. Most participants (52%) described their cervical dystonia as mild to moderate with an average pain score of 5/10. Eighty-two (64%) participants were having regular BoNT injections, with overall positive perceived effects. Common activities reported to improve the symptoms were the use of heat packs, massage, relaxation, physiotherapy and participation in general exercise. Common coping strategies reported were getting sufficient rest, having the support of friends and family, and remaining engaged in enjoyable hobbies. We found that most participants received regular BoNT injections and that heat packs, exercise, massage, physiotherapy and relaxation were mostly perceived as effective in reducing the symptoms of cervical dystonia.

A cross-sectional study of walking, balance and upper limb assessment scales in people with cervical dystonia.

Cervical dystonia (CD) is a neurological movement disorder causing the neck to move involuntarily away from the neutral position. CD is a network disorder, involving multiple brain areas and, therefore, may impair movement in parts of the body other than the neck. This study used clinical assessments to investigate walking, balance and upper limb function (UL) in people with CD; the reliability of scoring these assessments and examined for relationship between CD severity, usual exercise and clinical assessments. We conducted a prospective observational cohort study of participants with isolated, focal, idiopathic CD. Participants were assessed by experienced physiotherapists and completed three questionnaires and eight clinical assessments of fear of falling, balance confidence, walking, balance, UL function and usual exercise. Results were compared to published data from healthy adults and other neurological populations. Twenty-two people with mild to moderate CD participated. Fear of falling, gross UL function and usual exercise were worse in people with CD compared with healthy adults, while walking, balance and distal UL function were similar to healthy populations. All assessments were reliably performed by physiotherapists, and we found no correlations between the severity of dystonia or usual exercise and performance on the physical assessments. Routine performance of clinical assessment of walking and balance are likely not required in people with mild to moderate CD; however, fear of falling and gross upper limb function should be assessed to determine any problems which may be amenable to therapy.

Fall-related hospitalization in people with Parkinson's disease.

BACKGROUND AND PURPOSE: Falls are common in people with Parkinson's disease (PD) but few data exist on fall-related hospitalizations in this group. This population-based study compared fall-related hospital admissions, injury rates and consequences in people with and without PD, and determined whether PD was an independent predictor of fall-related hospital length of stay. METHODS: This was a retrospective study using probabilistic linkage of hospital data in people aged ≥65 years hospitalized for a fall between 1 July 2005 and 31 December 2013 in New South Wales, Australia. Rates of hospital admissions and injuries per person admitted over the study period were compared between people with and without PD using Poisson or negative binomial regression. Multilevel linear modelling was used to analyse length of stay by clustering individuals and adjusting for possible confounders. RESULTS: There were 342 265 fall-related hospital admissions in people aged ≥65 years during the study period, of which 8487 (2.5%) were for people with PD. Sixty-seven per cent of fall-related PD admissions were associated with injury and 35% were associated with fracture. People with PD had higher rate ratios for fall admissions (1.63, 95% confidence interval 1.59-1.67) and injury (1.47, 95% confidence interval 1.43-1.51) and longer median length of stay [9 (interquartile range 1-27) vs. 6 (interquartile range 1-20) days in people without PD; P < 0.001]. PD remained associated with increased length of stay after controlling for comorbidity, age, sex and injury (P < 0.001). CONCLUSIONS: This study provides important benchmark data for hospitalizations for falls and fall injuries for older people with PD, which may be used to monitor the effect of fall prevention programmes.

Evolution of Carotid Surgical Practice in the last Decade.

Stroke units provide immediate care and appropriate intervention in the evolving stroke. The aims of this study were to review the practice of carotid endarterectomy (CEA) before and after the establishment of a Stroke Unit in St. James's Hospital. Prior to the introduction of the Stroke Unit, 263 CEA's were performed over a five-year period. 139/263 (53%) of these were for symptomatic disease. 229 were performed in the five years since. 179/229 (78%) of these were for symptomatic disease. The 30-day stroke and death rates were < 2% before the introduction of the Stroke Unit, and have remained unchanged. Since the introduction of the Stroke Unit, there has been a slight decrease in the overall number of CEA's performed with a 25% increase in the proportion of endarterectomies performed for symptomatic disease. Despite the reduction in surgery for asymptomatic disease the overall 30-day stroke and death rate remains excellent at 2/229 (2%).

Going paperless: improved cataract surgery outcome data quality in a new fully electronic unit.

OBJECTIVES: To report outcome data on the first 5000 consecutive cataract cases at a new paperless eye unit and benchmark against the Royal College of Ophthalmologists' National Ophthalmology Database (RCOphth NOD). METHODS: Using the in-built audit tool of the electronic medical records system, data from all cataract operations performed between 1 April 2014 and 13 January 2017 were compiled. RESULTS: Five thousand and eight cases were recorded of which the overall intra-operative complication rate was 2.4%, the most common being posterior capsular rupture-1.14%. Follow-up data on post-operative complications were recorded in 98.6% of cases. Pre- and post-operative visual acuities was measured in 98.0% of cases. In all, 40.8% of eyes achieved a visual acuity of 6/6 or better and 90.7% achieved 6/12 or better. CONCLUSIONS: A data set of >5000 consecutive cataract operations was obtained in this eye department. The recording of pre- and post-operative visual acuity in 98% of cases compare very favourably to the RCOphth NOD Audit Report 2017 where pre- and post-operative visual acuities were recorded in only 57.1% of operations. Despite this difference, the outcome measures from this unit and RCOphth NOD were very similar, validating the results of the RCOphth NOD audit reports. Significantly, when applying the RCOphth NOD audit criteria for measuring post-operative visual acuity, approximately 15% of cases were excluded from the data set, reducing the completeness of the data set. Paperless ophthalmology units are feasible in today's NHS and can produce near complete cataract data sets; this can ultimately lead to more comprehensive and reliable aggregate cataract outcome data.

Detection of a potent humoral response associated with immune-induced remission of chronic myelogenous leukemia.

The effectiveness of donor-lymphocyte infusion (DLI) for treatment of relapsed chronic myelogenous leukemia (CML) after allogeneic bone marrow transplantation is a clear demonstration of the graft-versus-leukemia (GVL) effect. T cells are critical mediators of GVL, but the antigenic targets of this response are unknown. To determine whether patients who respond to DLI also develop B-cell immunity to CML-associated antigens, we analyzed sera from three patients with relapsed CML who achieved a complete molecular remission after infusion of donor T cells. Sera from these individuals recognized 13 distinct gene products represented in a CML-derived cDNA library. Two proteins, Jkappa-recombination signal-binding protein (RBP-Jkappa) and related adhesion focal tyrosine kinase (RAFTK), were recognized by sera from three of 19 DLI responders. None of these antigens were recognized by sera from healthy donors or patients with chronic graft-versus-host disease. Four gene products were recognized by sera from CML patients treated with hydroxyurea and nine were detected by sera from CML patients who responded to IFN-alpha. Antibody titers specific for RAFTK, but not for RBP-Jkappa, were found to be temporally associated with the response to DLI. These results demonstrate that patients who respond to DLI generate potent antibody responses to CML-associated antigens, suggesting the development of coordinated T- and B-cell immunity. The characterization of B cell-defined antigens may help identify clinically relevant targets of the GVL response in vivo.

Inter-limb coordination in bimanual reach-to-grasp following stroke.

Purpose. To determine the extent to which inter-limb coordination in the execution of unimanual and bimanual tasks was impaired following stroke.Methods. Thirteen stroke survivors aged 55 - 77 years and 13 healthy, neurologically intact participants aged 57 - 86 years performed a unimanual and two bimanual tasks involving the relocation of single and paired objects. Movements were recorded using electromagnetic sensors attached to the wrists and a series of micro switches placed under the objects. Main outcome measures included time to complete components of the tasks; comparison between sides; deviation of the hands from a linear trajectory; coordination of the two sides as indicated by relative phase angle.Results. Stroke survivors took longer to complete the bimanual tasks, but did not deviate from the optimal trajectories more than the healthy participants. Both groups performed unimanual tasks faster than bimanual and stroke participants were only slightly less synchronised when performing bimanual tasks.Conclusions. In conclusion, in a group of stroke patients with reasonable strength, inter-limb coordination was mildly impaired. This impairment in coordination was not due to lateral deviation of the impaired limb.

Comparative outcomes of T-cell-depleted and non-T-cell-depleted allogeneic bone marrow transplantation for chronic myelogenous leukemia: impact of donor lymphocyte infusion.

PURPOSE: Donor lymphocyte infusion (DLI) can restore complete remission in patients with chronic myelogenous leukemia (CML) who have relapsed after T-cell-depleted (TCD) allogeneic bone marrow transplantation (BMT). The existence of salvage treatment for patients with DLI after TCD allogeneic BMT prompted an evaluation of overall outcome after CD6+ -TCD allogeneic BMT for patients treated during the time when DLI has been available. PATIENTS AND METHODS: We performed a retrospective analysis of outcomes of 46 patients who underwent TCD allogeneic BMT for stable-phase CML and compared these outcomes with those of 40 patients who underwent non-TCD allogeneic BMT. All subjects were patients at one of two neighboring institutions during a period when DLI was available. All patients received marrow from HLA-identical sibling donors, underwent similar myeloablative regimens, and had similar pretreatment characteristics. RESULTS: After BMT, the TCD group had a lower incidence of grade 2 to 4 acute (15% v 37%, P = .026) and chronic graft-versus-host disease (GVHD) (18% v 42%, P = .024) than did the non-TCD group. The 1-year treatment-related mortality rates for the TCD group and the non-TCD group were 13% and 29%, respectively (P = .07). The estimated 3-year probability of relapse (cytogenetic or hematologic) was higher for patients in the TCD group than for patients in the non-TCD group (62% v 24%, P = .0003). Twenty-three patients (20 in the TCD group and three in the non-TCD group) received and were assessable for response to DLI. After DLI, 17 of 20 patients in the TCD group and two of three patients in the non-TCD group achieved complete remission. Donor lymphocyte infusion induced GVHD in nine of 23 patients. Thirty (65%) of 46 patients in the TCD group and 27 (69%) of 39 assessable patients in the non-TCD group remained alive without evidence of disease. The estimated 3-year overall survival rates were similar for the TCD group and the non-TCD group (72% v 68%, respectively; P = .38). At last follow-up, there was no difference in the overall prevalence of GVHD or the proportion of patients requiring immunosuppressive agents between groups. CONCLUSION: These results suggest that the combination of T-cell depletion and post-BMT DLI is a viable treatment option for patients undergoing allogeneic BMT for CML and should be prospectively compared with traditional forms of GVHD prophylaxis.

Phase I evaluation of intravenous recombinant human interleukin 12 in patients with advanced malignancies.

A Phase I dose escalation trial of i.v. administered recombinant human interleukin 12 (rhIL-12) was performed to determine its toxicity, maximum tolerated dose (MTD), pharmacokinetics, and biological and potential antineoplastic effects. Cohorts of four to six patients with advanced cancer, Karnofsky performance >/=70%, and normal organ function received escalating doses (3-1000 ng/kg/day) of rhIL-12 (Genetics Institute, Inc.) by bolus i.v. injection once as an inpatient and then, after a 2-week rest period, once daily for five days every 3 weeks as an outpatient. Therapy was withheld for grade 3 toxicity (grade 4 hyperbilirubinemia or neutropenia), and dose escalation was halted if three of six patients experienced a dose-limiting toxicity (DLT). After establishment of the MTD, eight more patients were enrolled to further assess the safety, pharmacokinetics, and immunobiology of this dose. Forty patients were enrolled, including 20 with renal cancer, 12 with melanoma, and 5 with colon cancer; 25 patients had received prior systemic therapy. Common toxicities included fever/chills, fatigue, nausea, vomiting, and headache. Fever was first observed at the 3 ng/kg dose level, typically occurred 8-12 h after rhIL-12 administration, and was incompletely suppressed with nonsteroidal anti-inflammatory drugs. Routine laboratory changes included anemia, neutropenia, lymphopenia, hyperglycemia, thrombocytopenia, and hypoalbuminemia. DLTs included oral stomatitis and liver function test abnormalities, predominantly elevated transaminases, which occurred in three of four patients at the 1000 ng/kg dose level. The 500 ng/kg dose level was determined to be the MTD. This dose, administered by this schedule, was associated with asymptomatic hepatic function test abnormalities in three patients and an onstudy death due to Clostridia perfringens septicemia but was otherwise well tolerated by the 14 patients treated in the dose escalation and safety phases. The T1/2 elimination of rhIL-12 was calculated to be 5.3-9.6 h. Biological effects included dose-dependent increases in circulating IFN-gamma, which exhibited attenuation with subsequent cycles. Serum neopterin rose in a reproducible fashion regardless of dose or cycle. Tumor necrosis factor alpha was not detected by ELISA. One of 40 patients developed a low titer antibody to rhIL-12. Lymphopenia was observed at all dose levels, with recovery occurring within several days of completing treatment without rebound lymphocytosis. There was one partial response (renal cell cancer) and one transient complete response (melanoma), both in previously untreated patients. Four additional patients received all proposed treatment without disease progression. rhIL-12 administered according to this schedule is biologically and clinically active at doses tolerable by most patients in an outpatient setting. Nonetheless, additional Phase I studies examining different schedules and the mechanisms of the specific DLTs are indicated before proceeding to Phase II testing.

Supportive devices for preventing and treating subluxation of the shoulder after stroke.

BACKGROUND: Supportive devices such as slings, wheelchair attachments and orthoses have been used to treat subluxation of the shoulder after stroke. OBJECTIVES: To investigate the effect of supportive devices in preventing subluxation, re-positioning the head of humerus in the glenoid fossa, decreasing pain, increasing function and adversely increasing contracture in the shoulder after stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched on 22 March 2004). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2004), MEDLINE (1966 to March 2004), CINAHL (1982 to March 2004), EMBASE (1974 to March 2004), AMED (1985 to March 2004) and the Physiotherapy Evidence Database (PEDro, March 2004). We also handsearched conference proceedings and contacted authors for additional information. SELECTION CRITERIA: Studies were included if they were: randomised, quasi-randomised or controlled trials; participants had a stroke; intervention was supportive devices; and subluxation, pain, function or contracture were measured. DATA COLLECTION AND ANALYSIS: Two independent reviewers examined the identified studies which were assessed for methodological quality and analysed as (1) supportive devices versus no supportive devices or (2) two supportive devices. MAIN RESULTS: Four trials (one on slings, three on strapping - 142 participants) met the inclusion criteria. One trial testing a hemisling versus no device reported that no participants had subluxation greater than 10 mm, the same number had lost more than 30 degrees of shoulder external rotation (Peto odds ratio (OR) = 1.00, 95% confidence interval (CI) 0.1 to 9.3), and more participants in the hemisling group had pain (Peto OR = 8.7, 95% CI 1.1 to 67.1). The other three showed that strapping was effective in delaying the onset of pain (weighted mean difference (WMD) = 14 days, 95% CI 9.7 to 17.8), but was ineffective in reducing pain severity (WMD = -0.7 cm on a visual analogue scale, 95% CI -2.0 to 0.7), increasing upper limb function (WMD = 0.8, 95% CI -1.5 to 3.1) or affecting the degree of contracture (WMD = -1.4 degrees, 95% CI -10.9 to 8.1) at the shoulder. AUTHORS' CONCLUSIONS: There is insufficient evidence to conclude whether slings and wheelchair attachments prevent subluxation, decrease pain, increase function or adversely increase contracture in the shoulder after stroke. There is some evidence that strapping the shoulder delays the onset of pain but does not decrease it, nor does it increase function or adversely increase contracture.

Fenestrated endovascular repair of complex aortic aneurysms.

BACKGROUND: Fenestrated endovascular aneurysm repair (FEVAR) provides an endovascular solution for patients with large abdominal aortic aneurysms and challenging neck anatomy in addition to repair of endoleaks and pseudoaneurysms. This article reports the midterm outcomes of FEVAR from a single-tertiary referral centre in Ireland. METHODS: From 2006 to 2012, nine consecutive asymptomatic patients with neck anatomy unfavourable for standard EVAR underwent endovascular repair with a customised fenestrated Zenith stent graft. An additional three patients had fenestrated grafts for repair of pseudoaneurysms (n = 2) following open AAA repair and a type I endoleak (n = 1). All patients were prospectively enrolled in a computerised database. Outcomes including mortality, morbidity, renal function, target vessel patency, endoleak and reintervention were analysed. FINDINGS: The mean age and aneurysm size in the primary repair group were 74 years (65-84 years) and 6 cm (5-8.3 cm), respectively, and in the secondary repair group, the mean age was 66 years (61-75 years). No procedures required open conversion, and no visceral arteries were lost. On completion angiography, two patients in group 1 had a type I endoleak and one had a type III endoleak. There were no endoleaks in the secondary repair group. Follow-up ranged from 30 days to 6 years. There was one death within 30 days (8 %) and two deaths at 3 years from non-aneurysm-related causes. Six patients required secondary interventions. Three patients had a transient post-operative creatinine rise of >30 %. CONCLUSION: Our study supports FEVAR as a feasible and effective therapy in the management of patients with complex aortic aneurysms.

A MultiCenter Pilot Randomized Controlled Trial of Remote Ischemic Preconditioning in Major Vascular Surgery.

A pilot randomized controlled trial that evaluated the effect of remote ischemic preconditioning (RIPC) on clinical outcomes following major vascular surgery was performed. Eligible patients were those scheduled to undergo open abdominal aortic aneurysm repair, endovascular aortic aneurysm repair, carotid endarterectomy, and lower limb revascularization procedures. Patients were randomized to RIPC or to control groups. The primary outcome was a composite clinical end point comprising any of cardiovascular death, myocardial infarction, new-onset arrhythmia, cardiac arrest, congestive cardiac failure, cerebrovascular accident, renal failure requiring renal replacement therapy, mesenteric ischemia, and urgent cardiac revascularization. Secondary outcomes were components of the primary outcome and myocardial injury as assessed by serum troponin values. The primary outcome occurred in 19 (19.2%) of 99 controls and 14 (14.1%) of 99 RIPC group patients (P = .446). There were no significant differences in secondary outcomes. Our trial generated data that will guide future trials. Further trials are urgently needed.

A CD4+ T cell clone selected from a CML patient after donor lymphocyte infusion recognizes BCR-ABL breakpoint peptides but not tumor cells.

BACKGROUND: In patients with chronic myelocytic leukemia (CML), the breakpoint cluster region and fusion between the BCR and the c-ABL genes (BCR-ABL) oncogen product is a potential tumor-specific antigen. Previous studies have shown that T cells specific for the junctional region peptides of the BCR-ABL oncoprotein can be detected in healthy individuals as well as in patients with CML in chronic phase. We assessed whether BCR-ABL- specific T cells could be found in a patient achieving a complete cytogenetic remission after CD4+ donor lymphocyte infusion. METHODS: Using dendritic cells pulsed with BCR-ABL breakpoint peptides as antigen-presenting cells, we stimulated patient peripheral blood lymphocytes to isolate peptide-specific T cell clones present at the time of the cytogenetic response. T cell clones were isolated and the cellular specificity of these cells was examined. RESULTS: A CD3+ CD4+ T cell clone (1F7) that recognizes overlapping p210 junctional peptides presented by HLA-DR molecules was identified and expanded in vitro. Clone 1F7 failed to recognize autologous tumor cells as well as dendritic cells derived from patient CML cells. Clone 1F7 did not inhibit the growth and differentiation of CML precursor cells in a standard colony formation assay. Finally, using a clone-specific probe, 1F7 cells could not be detected in patient peripheral blood at the time of the donor lymphocyte infusion response. CONCLUSIONS: These results suggest that clone 1F7 was selected in vitro using highly potent peptide pulsed dendritic cells but was not representative of the anti-leukemia immune response in vivo. Based on these findings, CD4+ T cells with BCR-ABL specificity do not appear to be mediators of the anti-leukemia response in vivo after donor lymphocyte infusion.

Derivation of adherence metrics from electronic dosing records.

Numerous adherence variables have been created from electronic dosing records hindering synthesis of the vast body of adherence research. To elucidate the mathematical foundation for electronic adherence monitoring and to understand how diverse electronic adherence metrics are related to each other and the underlying construct of adherence behavior. Several representative adherence metrics are derived mathematically and their relationship to the underlying consumption (or dosing event) rate analyzed. Data from a 3-month study of 286 individuals on single-drug antihypertensive therapy are then used to empirically study the statistical properties of several of these electronic adherence metrics. As suggested by their common link to the consumption (or dosing event) rate, the analyzed electronic adherence metrics were generally strongly correlated (r <- .6 and > .4). The lowest correlation (r = .15) involved the ratio of the observed number of doses to the recommended number (called average adherence), which tended to emphasize quantity consumed, and the ratio of the observed to maximum mean squared rate deviation (MSRD ratio), which focused more on dose timing. Despite their different formulations, electronic adherence variables are generally closely correlated. Adherence metrics that average the consumption rate over multiple doses (by summing up the number of doses and dividing by the monitored time) may be less sensitive to short-term fluctuations in medication intake. Metrics that are more sensitive to timing variability may thus be preferable when timing as well as quantity of dosing are of interest.

CD8+ cell depletion of donor lymphocyte infusions using cd8 monoclonal antibody-coated high-density microparticles (CD8-HDM) after allogeneic hematopoietic stem cell transplantation: a pilot study.

A CD8 murine monoclonal antibody-coated high-density microparticle (HDM) has been developed, which allows for the rapid depletion of CD8+ T cells from apheresis products by gravity sedimentation. We conducted a study to determine the efficacy and safety of CD8 depletion of donor lymphocyte infusions (DLI) to treat relapse after stem cell transplantation using the Eligix CD8-HDM Cell Separation System. Patients were targeted to receive 3 x 10(7) CD4+ T cells/kg. Nine patients were enrolled, three with CML, three myeloma, two CLL, and one NHL. A median of 1 x 10(10) mononuclear cells were obtained by apheresis and processed. The median depletion of CD8+ cells was 99.3% (97.8->99.5%). CD8 depletion was highly specific, with a median recovery of CD4+ cells of 75%. A median of 2.9 x 10(7) CD4+ cells/kg was infused. No infusional toxicity was noted. All CML patients achieved a complete molecular remission. A CLL patient demonstrated a complete response. One patient developed GVHD (grade II acute GVHD and subsequently chronic GVHD). The CD8-HDM Cell Separation System appears to be highly selective and effective in depleting CD8+ T cells from DLI apheresis products, and CD8-depleted DLI is capable of mediating a graft-versus-leukemia effect while minimizing GVHD.

Changes in T cell receptor repertoire associated with graft-versus-tumor effect and graft-versus-host disease in patients with relapsed multiple myeloma after donor lymphocyte infusion.

Recent reports of clinical responses following donor lymphocyte infusions (DLI) in patients with relapsed multiple myeloma (MM) after allogeneic BMT have demonstrated the ability of allogeneic cells to mediate a graft-versus-myeloma (GVM) effect, but the mechanisms involved have not been determined. To identify changes in the T cell compartment associated with DLI, we performed a molecular analysis of the T cell receptor (TCR) repertoire in four patients with relapsed MM who received infusions of CD4+ lymphocytes from HLA-identical sibling donors. Three of the four patients demonstrated a clinical anti-myeloma response following DLI but also developed graft-versus-host disease (GVHD). The TCR repertoire was examined after PCR amplification of 24 Vbeta gene subfamilies. This method determines the relative utilization of each Vbeta gene subfamily and also allows the identification of clonal and oligoclonal T cell populations through analysis of CDR3 regions for each TCR Vbeta gene subfamily. Serial blood samples were obtained over at least a 1 year period before and after DLI and results compared to 10 normal donors. Serial analysis of CDR3 size profiles demonstrated the appearance of clonal T cell populations after DLI in each of the three responding patients. The appearance of some clones was noted within the first 3 months after DLI and coincided with decreasing levels of monoclonal paraprotein indicating an ongoing GVM response. Other T cell clones appeared at later time points and coincided with the development of GVHD. These findings demonstrate that T cell clones with different patterns of onset can be identified in the peripheral blood of MM patients following DLI. Further functional characterization of these distinct clonal expansions will be required to determine whether these T cell clones are mediators of either anti-myeloma or anti-host activity.

Outcome after autologous and allogeneic stem cell transplantation for patients with multiple myeloma: impact of graft-versus-myeloma effect.

A total of 228 patients with multiple myeloma (MM), 166 patients receiving autologous transplantation (124 PBSC and 38 BM) and 66 patients receiving T-cell-depleted allogeneic transplantation were analyzed to compare overall survival (OS), progression-free survival (PFS) and risk of relapse. Patients receiving autologous transplantation had a significantly improved OS (P=0.006) and PFS (P=0.002) at 2 years with OS and PFS for autologous transplant 74% and 48%, respectively, compared with 51% and 28% for allogeneic transplantation. By 4 years after transplantation, outcome was similar with OS and PFS for autologous transplantation 41% and 23%, respectively, compared with 39% and 18% for allogeneic transplantation. The 4-year cumulative incidence of nonrelapse mortality was significantly higher in patients receiving allogeneic transplantation (24% vs 13%) (P=0.004). Relapse was the principle cause of treatment failure for both groups; however, there was a significantly reduced risk of relapse associated with allogeneic transplantation at 4 years: 46% for allograft vs 56% for autograft (P=0.02). Despite a lower risk of relapse after allogeneic transplantation, autologous transplantation is associated with improved OS and PFS compared with allogeneic transplantation in patients with MM. Strategies focused on reducing nonrelapse mortality in allogeneic transplantation may translate into an improved outcome for patients receiving allogeneic transplantation.

Using argon laser blue light reduces ophthalmologists' color contrast sensitivity. Argon blue and surgeons' vision.

Color contrast sensitivity was measured in laser operators before and after laser use. After argon blue-green laser treatment sessions, sensitivity was reduced for colors lying along a tritan color-confusion line for several hours. This acute effect is due to specular "flash-backs" from the aiming beam off the surface of the contact lens. It is caused only by argon 488-nm light, when the aiming beam intensity is high. In addition, a correlation has been demonstrated between the number of years of laser experience and a chronic reduction in tritan color contrast sensitivity. It is suggested that repeated acute changes caused by the argon lasers may cause cumulative effects and produce a chronic threshold elevation. A simple method of eliminating the acute effect is documented.

Alterations in Ca2+ signal transduction in critically ill surgical patients.

BACKGROUND: Despite improvements in supportive care and pharmacologic therapies, sepsis and related disorders such as systemic inflammatory response syndrome (SIRS) continue to be a leading cause of death in the intensive care unit. We hypothesized that immune dysfunction in this setting may in part be mediated at the level of early signal transduction in monocytes and neutrophils as manifested by changes in intracellular free Ca2+. METHODS: Monocytes and neutrophils were isolated from patients in the intensive care unit who met the criteria for SIRS and from normal volunteers. Cells were loaded with the Ca(2+)-sensitive fluorescent dye Indo-1 and stimulated with the chemotactic peptide f-Met-Leu-Phe (fMLP). Changes in intracellular calcium ion concentration were measured by flow cytometry. RESULTS: Patient monocytes exhibited a decreased Ca2+ flux (43% +/- 3.1%) as compared with normal monocytes (63% +/- 2.5%) (p < 0.05). Patient neutrophils also exhibited a decreased Ca2+ flux in response to fMLP of 58% +/- 3.7% versus 69.3% +/- 3.1% for normal neutrophils (p < 0.05). Incubation of patient cells in normal plasma reversed this dysfunction and showed an improved Ca2+ flux to 60% +/- 2.7% for monocytes and 71% +/- 3.7% for neutrophils (p < 0.05). Conversely, calcium flux was decreased in both normal monocytes (42.3% +/- 3.1%) and normal neutrophils (55.4% +/- 3.8%) after incubation in SIRS patient plasma (p < 0.05). Incubation of normal monocytes and neutrophils in interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor, or lipopolysaccharide did not show a statistically significant alteration in calcium flux in response to fMLP. CONCLUSIONS: Patients with SIRS exhibit alterations in early signal transduction after stimulation with fMLP in monocytes and neutrophils. This effect appears to be mediated by a soluble factor because the defect in SIRS patient cells can be reversed by incubation in normal plasma and normal cells appear to acquire this defect after incubation in patient plasma. Further studies are underway to identify the factor or factors responsible for this functional defect.