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Biomedical subjects

J Lipton

Publications and source records attributed to J Lipton.

At least 37 records · Page 2Linked to original sources
PubMed1999

Elevated serum cytokines are associated with cytomegalovirus infection and disease in bone marrow transplant recipients.

To assess the relationship between serum cytokines and cytomegalovirus (CMV) reactivation, 75 allogeneic bone marrow transplant patients underwent weekly measurements of interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-alpha, CMV blood cultures, and antigenemia tests. Of the patients, 44 (58.7%) developed CMV infection, and 19 (25.3%) developed clinical CMV disease. The mean maximum levels of all three cytokines were significantly increased in patients with CMV infection compared with levels in those without. Maximum levels of IL-6 were significantly higher in patients with active CMV disease than in those who did not develop CMV disease (281.2+/-85.5 vs. 95.7+/-15.0 pg/mL; P=.034). Levels of IL-8 and TNF-alpha were also elevated in patients who developed active disease. In a multivariate logistic regression model, IL-6 levels were independently associated with CMV disease (odds ratio=1.70 per 100-pg/mL increase in IL-6; P=.009). Cytokines may play an important role in the pathogenesis of CMV after bone marrow transplantation and may be a useful predictor for CMV.

Adult↗
PubMed1998

Clinical and economic analysis of allogeneic peripheral blood progenitor cell transplants: a Canadian perspective.

Allogeneic peripheral blood progenitor cell (PBPC) transplants are an alternative to BMT, although G-CSF mobilization dose, timing of pheresis and risk of GVHD are not well defined. We compared harvest characteristics, donor and recipient outcomes and costs of two PBPC transplant strategies with historical controls who received BMT. Twenty donors mobilized with four daily s.c. G-CSF doses (5 microg/kg/day) (group 1) and 20 mobilized with 10 microg/kg/day G-CSF (group 2) were compared with 20 BM controls (group 3). G-CSF and phereses were well tolerated. Four of 40 PBPC donors required femoral catheter placement. At least 2.5 x 10(6) CD34+/kg recipient weight were collected with two phereses in 19/20 donors (group 1) and 18/20 donors (group 2). Time to neutrophil (18 vs 20 vs 22 days, P = 0.02) and platelet (21 vs 24 vs 27 days, P = 0.005) engraftment was shorter in the PBPC groups (group 2 vs group 1 vs group 3) but secondary engraftment outcomes were not different. The incidence of grade 2-4 aGVHD was higher in the low-dose G-CSF group (group 1) but there was no difference in cGVHD, 100-day or 1-year survival. The mean PBPC transplant cost (group 1) at first hospital discharge was less than BM (group 3) ($34,643 vs $37,354) but the mean overall cost for both groups was similar at 100 days ($46,334 vs $46,083). Allogeneic PBPC transplant with short course, low-dose G-CSF mobilization is safe, feasible and cost equivalent to allogeneic BMT.

Bone Marrow Transplantation↗
PubMed1998

Effect of cytomegalovirus infection on 1-year mortality rates among recipients of allogeneic bone marrow transplants.

The effect of cytomegalovirus (CMV) infection on 1-year mortality rates among allogeneic bone marrow transplant recipients who are receiving a standard protocol as prophylaxis for CMV infection is unclear. We determined the risk factors for death within 1 year among 103 bone marrow transplant recipients by performing a multivariate analysis. The results of donor and recipient CMV serologies did not predict 1-year mortality, although there was a trend towards higher mortality among CMV-seropositive recipients who received marrow from seronegative donors (P = .077). Multivariate analysis revealed that the factors independently associated with 1-year mortality were the development of CMV antigenemia (relative risk [RR] = 2.74; confidence interval [CI] = 1.28-5.86), bone marrow transplantation (BMT) from unrelated donors (RR = 3.20; CI = 1.30-7.92), and severe acute graft-versus-host disease (RR = 3.50; CI = 1.50-8.17). Although significant on univariate analysis, advanced underlying disease before BMT and the development of active CMV disease after BMT were not independent risk factors. In conclusion, the development of CMV antigenemia after BMT was associated with increased 1-year mortality, while the development of active CMV disease was not. Reactivation of CMV infection may represent a marker of poor immune reconstitution or may contribute to further immunosuppression after BMT.

Adolescent↗
PubMed1997

Evaluation of critical body residue QSARs for predicting organic chemical toxicity to aquatic organisms.

The critical body residue (CBR) is the concentration of chemical bioaccumulated in an aquatic organism that corresponds to a defined measure of toxicity (e.g., mortality). The CBR can provide an alternative measure of toxicity to traditional waterborne concentration measurements (e.g., concentration in water causing 50% mortality). The CBR has been suggested as a better estimator of dose than the external water concentration and has been postulated to be constant for chemicals with the same mode of action. CBR QSARs have both theoretical and experimental support, developed primarily from studies on the acute toxicity of narcotic chemicals to small fish. CBR QSARs are less well developed for the aquatic toxicity of non-narcotic chemicals. CBRs vary substantially with the mode of action and toxicity endpoint, and may be affected by genetic, hormonal or environmental variation. CBR QSARs may not be applicable to very hydrophobic chemicals, chemicals with specific modes of action, or those with toxicity controlled by kinetic processes such as biotransformation. CBRs models have not been developed or evaluated for sediment and dietary exposure routes. Application of CBR QSARs to contaminated site assessments will require further research and development.

Animals↗
PubMed1996

Alpha-melanocyte-stimulating hormone reduces endotoxin-induced liver inflammation.

Alpha-Melanocyte-stimulating hormone (MSH) is a potent anti-inflammatory agent in many models of inflammation, suggesting that it inhibits a critical step common to different forms of inflammation. We showed previously that alpha-MSH inhibits nitric oxide (NO) production in cultured macro-phages. To determine how alpha-MSH acts in vivo, we induced acute hepatic inflammation by administering endotoxin (LPS) to mice pretreated with Corynebacterium parvum, alpha-MSH prevented liver inflammation even when given 30 min after LPS administration. To determine the mechanisms of action of alpha-MSH, we tested its influence on NO, infiltrating inflammatory cells, cytokines, and chemokines. Alpha-MSH inhibited systemic NO production, hepatic neutrophil infiltration, and increased hepatic mRNA abundance for TNF alpha, and the neutrophil and monocyte chemokines (KC/IL-8 and MCP-1). We conclude that alpha-MSH prevents LPS-induced hepatic inflammation by inhibiting production of chemoattractant chemokines which then modulate infiltration of inflammatory cells. Thus, alpha-MSH has an effect very early in the inflammatory cascade.

Animals↗
PubMed1996

Acute anterior uveitis in juvenile Reiter's syndrome.

We describe the case of an acute anterior uveitis (AAU) and reactive arthritis following a gastrointestinal infection of Salmonella typhimurium in a 9-year-old girl. Reiter's syndrome mainly affects men and is unusual in children especially in young females.

Acute Disease↗
PubMed1996

Detection of donor cell derived acute myelogenous leukaemia in a patient transplanted for chronic myelogenous leukaemia using fluorescence in situ hybridization.

The recurrence of leukaemia following allogeneic bone marrow transplantation appears to develop rarely in donor cells. However, the standard method for assigning the origin of recurrence, metaphase analysis, can be unreliable. We have applied the technique of fluorescence in situ hybridization (FISH) directly on archival Wright stained bone marrow slides obtained from a patient who developed acute myelogenous leukaemia (AML) following allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukaemia (CML). Using a chromosome-specific DNA probe we linked a chromosomal aberration, previously detected by conventional metaphase analysis, directly to morphologically identifiable blast cells. In this way we were able to assess cell-lineage involvement of the secondary leukaemia and assign a donor origin.

Adult↗
PubMed1995

Isolated chloroma: the effect of early antileukemic therapy.

OBJECTIVE: To evaluate the effect of antileukemic chemotherapy administered at diagnosis on the survival of patients with isolated chloroma. DESIGN: Retrospective review of locally identified patients and analysis of cases from the medical literature. PATIENTS: The records of all patients with isolated chloroma identified at three teaching hospitals in Toronto between 1980 and 1994 were reviewed. A MEDLINE search was done to identify all cases of isolated chloroma reported in the English-language medical literature. Patients with a previous known hematologic disorder were excluded. MEASUREMENTS: The effect of therapy on 1) the interval between diagnosis of chloroma and diagnosis of acute myeloid leukemia and 2) survival was determined. RESULTS: 7 local patients and 83 published cases were identified, for a total of 90 evaluable patients. For the entire group, the median time to the diagnosis of acute myeloid leukemia was 9 months, and median survival was 22 months. Chemotherapy was administered to 49 patients (54%) at diagnosis of chloroma. Significantly fewer patients treated with chemotherapy subsequently developed acute myeloid leukemia (41% compared with 71%; P = 0.001). Survival was longer in patients treated with chemotherapy (> 50% alive with a median follow-up of 25 months compared with a median survival of 13 months for those initially untreated; P = 0.001). Multivariate analysis showed that neither local radiotherapy nor surgery had an effect on survival. CONCLUSIONS: Administration of antileukemic chemotherapy at diagnosis of chloroma is associated with a significantly lower probability of developing acute myeloid leukemia and with longer survival.

Acute Disease↗
PubMed1995

Short communication: selecting input distributions for use in Monte Carlo simulations.

Monte Carlo analysis is increasingly employed as a means of quantifying uncertainties in risk assessment. However, the output of any Monte Carlo analysis is extremely sensitive to the input distributions used. In this paper we present a simple set of guidelines for the selection of input distributions. The guidelines involve allocating variables with unknown distributions to appropriate distributional "classes," based on the range of possible values that could be obtained for the data and known characteristics about the behavior of the variable. If the class of distribution is not identifiable, then variables can be related to a specific distribution using goodness-of-fit techniques. If these identification schemes fail, bootstrapping techniques may be used to generate a sampled distribution from the available data. Finally, "default" distributions may be employed using analogous data if site-specific data are unavailable.

Mathematics↗
PubMed1994

Secondary malignancies after bone marrow transplantation in adults.

PURPOSE: The records of 557 consecutive adult recipients of allogeneic-related and -unrelated and syngeneic bone marrow transplants (BMTs) were reviewed to determine the incidence of secondary cancers. PATIENTS AND METHODS: Four hundred fifty-six patients were transplanted for acute lymphocytic leukemia (ALL; n = 79), acute myelogenous leukemia (AML; n = 182), and chronic myelogenous leukemia (CML; n = 195); 42 patients were transplanted for aplastic anemia (AA) and 59 for a variety of other hematologic and nonhematologic disorders, malignant and nonmalignant. Conditioning regimens included high-dose chemotherapy with or without total-body irradiation (TBI). Statistical analyses determined the cumulative incidence of developing a secondary cancer and elucidated the associated risk factors. Complete records (1 to 24 years of follow-up) on all patients were available. RESULTS: Nine patients developed 10 secondary cancers for a cumulative actuarial risk of 12% (95% confidence interval [CI], 4.3 to 23.0) 11 years after transplant. The age-adjusted incidence of secondary cancer was 4.2 times higher than that of primary cancer in the general population. Eight of the 10 were epithelial in origin and three were cutaneous. TBI and acute graft-versus-host disease (GVHD) with a severity > or = grade II were associated with the development of any secondary cancer. On the other hand, chronic GVHD was a risk factor only for the development of secondary skin neoplasms. CONCLUSION: Adult recipients of BMT face a significant risk of developing a secondary malignancy. Their risk is similar to that of other patients with hematologic malignancies who are treated with chemoradiotherapy only. Epithelial tumors, rather than the more commonly reported Epstein-Barr virus (EBV)-associated lymphomas, were most common. The fact that we did not routinely use T-cell-depleted marrow grafts nor anti-T-cell immunoglobulin for the treatment of acute GVHD may explain this variance.

Adolescent↗
PubMed1994

Pneumatosis intestinalis with free air mimicking intestinal perforation in a bone marrow transplant patient.

A case of pneumatosis intestinalis with perforation is reported in a patient after bone marrow allograft for chronic myeloid leukemia. Risk factors included the transplant, prolonged immunosuppression and neutropenia, graft-versus-host disease, extended use of corticosteroids, infection and lower gastrointestinal endoscopic biopsy. The literature is reviewed and a management plan for patients presenting with this complication is discussed.

Adult↗
PubMed1992

Uncertainty in risk assessment: exceedence frequencies, acceptable risk, and risk-based decision making.

The use of "exceedence frequencies" is proposed as a means of evaluating the acceptability of uncertain environmental risks. A survey was conducted of U.S. Environmental Protection Agency personnel. When respondents were requested to identify preferred "acceptable" exceedence frequencies at four different regulatory risk thresholds (10(-3) to 10(-6), three general response patterns were found: "absolutist" responses in which no level of exceedence was deemed acceptable; "fixed" responses in which respondents felt that the level of exceedence should remain constant at all risk levels; and "outcome sensitive" responses in which preferred exceedence frequencies were inversely related to the risk level. This last group's responses were based on the rationale that the "marginal cost" of risk (in terms of expected mortalities) increases as the risk threshold increases. Although the majority of respondents accepted the concept of an acceptable risk exceedence frequency, the low exceedence frequencies selected as being "acceptable" by survey respondents (generally 5% or less) appear to be overly conservative given the degree of uncertainty inherent in risk assessments. Finally, two regulatory uses of exceedence frequencies are proposed as a tool for streamlined risk ranking.

Attitude of Health Personnel↗
PubMed1992

Detection of colour vision abnormalities in uncomplicated type 1 diabetic patients with angiographically normal retinas.

Colour vision function was assessed in 38 non-complicated type 1 diabetic patients in whom fluorescein angiography was normal, and was compared with that in 36 age-matched, non-diabetic controls. All of the patients were healthy and none were taking medication except insulin. The eye examination, which was normal in every patient, included the Ishihara and City University tests, measurement of Snellen acuity, slit-lamp examination, tonometry, and fundal photography as well as fluorescein angiography. Colour discrimination ability was measured with the Farnsworth-Munsell 100-hue test. Mean (SE) 100-hue test error score for the diabetic group was 86.8 (8.1) compared with 28.2 (3.3) for controls, p<<0.001. There was no relation between colour vision abnormalities and diabetes duration (r = 0, p>0.05), blood glucose at the time the colour tests were performed (r = 0.4, p > 0.05), most recent glycated haemoglobin result (r = 0.3, p>0.05), or the mean of all previous glycated haemoglobin results (r = 0, p>0.05). It is concluded that colour discrimination may be abnormal in uncomplicated type 1 diabetic patients before the onset of retinopathy, and that colour discrimination losses in diabetes may not be of vascular aetiology.

Adult↗
PubMed1991

Continuous cocaine administration produces persisting changes in brain neurochemistry and behavior.

Rats were administered either continuous cocaine, daily injections of cocaine, continuous amphetamine, or no drug for 5 days and then given a 30 day drug-free recovery period. When subsequently tested in open field, the daily cocaine injection animals were the most hyperactive whereas the cocaine pellet animals were the most fearful. In vitro autoradiography was then utilized to examine persisting changes in receptor binding for D2 ([3H]spiperone), D1 ([3H]SCH23390), benzodiazepine ([3H]flunitrazepam), 5-HT1 ([3H]5-HT), 5-HT2 ([3H]ketanserin), and muscarinic acetylcholine (ACh) receptors ([3H]QNB; quinuclidinyl benzilate). In the amphetamine pellet animals, there were large increases in [3H]spiperone binding in several dopamine (DA)-rich regions; these were accompanied by conversely decreased [3H]SCH23390 binding. Cocaine pellet animals showed a completely different pattern, with appreciable increases in [3H]flunitrazepam binding in DA-rich areas, cortex, and amygdala but decreased [3H]QNB binding in DA-rich areas, hippocampus, and amygdala. While cocaine injection animals showed elevated [3H]spiperone binding in caudate and substantia nigra, they had generally smaller changes in most brain regions than the other drug groups. These findings replicate and extend previous reports that continuous drug administration induces long-lasting alterations in brain chemistry, but indicate that continuous cocaine has enduring effects on different neurochemical systems from continuous amphetamine.

Amphetamine↗
PubMed1991

A silicone pellet for continuous cocaine: comparison with continuous amphetamine.

An inexpensive silicone pellet is described for the continuous administration of cocaine for up to 5 days. Rats implanted with this pellet show minimal skin irritation and go through distinct behavioral stages, with an initial period of hyperactivity followed by motor stereotypies. Then, at 3-4 days after implantation, a variety of hallucinogen-like ("late-stage") behaviors appear, including limb flicks, sudden startle responses, and repetitive mid-air grasping movements. Compared to continuous d-amphetamine, continuous cocaine induces decreased motor stereotypies but heightened "late-stage" behaviors.

Animals↗
PubMed1991

Treatment of strabismus after retinal detachment surgery with botulinum neurotoxin A.

Thirty-one consecutive patients were treated with injections of Botulinum Neurotoxin A to rectus muscles for strabismus following retinal detachment surgery. In 14 cases the presenting problem was diplopia and in 17 cases the presenting problem was cosmetic appearance. A total of 67 injections was given. Twenty-seven cases had nine months or more follow-up. Of these, four of 11 cases with diplopia had fusion restored, four were shown to have no fusion potential, and three had temporary improvement only. In 16 cases with a primary cosmetic problem there was no useful effect in two, three had surgery as an alternative, three were realigned long-term, and eight had continuing maintenance therapy with toxin. Over half the series had undergone multiple detachment surgery, often for giant tears and other complex pathology.

Adult↗