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Biomedical subjects

P Stewart

Publications and source records attributed to P Stewart.

At least 145 records · Page 8Linked to original sources
PubMed1986

Mortality among industrial workers exposed to formaldehyde.

A historical cohort study evaluated the mortality experience of 26,561 workers employed in 10 formaldehyde-producing or -using facilities. Approximately 600,000 person-years of follow-up accrued as workers were followed to January 1, 1980. Estimates of historical exposure to formaldehyde by job were developed by project industrial hygienists using monitoring data available from participating plants, comments from long-term workers, and comprehensive monitoring data specifically collected for this study. Mortality from all causes combined was about as expected [standardized mortality ratio (SMR) = 96] based on mortality rates of the general U.S. population. Significantly fewer deaths occurred from infective and parasitic diseases (SMR = 51) and from accidents (SMR = 72) than expected. Cancer overall was not related to formaldehyde exposure. Workers exposed to formaldehyde had slight excesses for Hodgkin's disease and cancers of the lung and prostate gland, but these excesses were not consistently related to duration of or average, cumulative, or peak formaldehyde exposure levels. Recent animal studies found nasal cancer among rats exposed to formaldehyde, but no excess of this tumor occurred in this study. Mortality from brain cancer and leukemia among these industrial workers was not excessive in contrast to reported excesses among professional groups (e.g., anatomists, embalmers, and pathologists) with exposure to formaldehyde. Although there was a deficit for cancer of the buccal cavity and pharynx, mortality from certain subsites, i.e., the nasopharynx and oropharynx, was elevated. These subsites did not, however, show a consistently rising risk with level of exposure. These data provide little evidence that mortality from cancer is associated with formaldehyde exposure at levels experienced by workers in this study.

Adult↗
PubMed1986

Detection of dyslipoproteinemia with the use of plasma total cholesterol and triglyceride as screening tests. The Lipid Research Clinics Program Prevalence Study.

The efficiency of screening for dyslipoproteinemias associated with hyperlipoproteinemia or with hypolipoproteinemia was examined in 8449 white examinees from the Lipid Research Clinics Prevalence Study. A two-stage lipid screening approach was used. A positive screening test for hyperlipidemia was defined as an elevated level of plasma total cholesterol or triglyceride at both visit 1 and visit 2. A positive screening test for hypolipidemia was defined as a reduced plasma total cholesterol level at both visits. The syndromes of dyslipoproteinemia were defined according to the lipoprotein pattern present at visit 2. When hyperlipidemia was used as a screening tool, generally only about one-half or less of the cases of hyperlipoproteinemia were detected (high proportion of false-negative results). Of all the hyperlipidemic participants, more than 80% had hyperlipoproteinemias (type I, IIa, IIb, III, IV, or V), and such lipid screening therefore provided a lower proportion of false-positive than false-negative results. Most of the participants (greater than 98%) without hyperlipoproteinemia were correctly identified (true negatives). The efficiency of screening for hypolipoproteinemia was in general poorer than that found for hyperlipoproteinemia. Our results were found to be related, in part, to the marked regression to the mean of plasma cholesterol and triglycerides at the extremes of the distributions and to the wide variety of dyslipoproteinemias that can be present within a given range of plasma cholesterol or triglyceride values. The results emphasize the importance of measuring plasma lipoproteins in the patient who is being evaluated for dyslipoproteinemia.

Adolescent↗
PubMed1986

Progeny's lipid and lipoprotein levels by parental mortality. The Lipid Research Clinics Program Prevalence Study.

Using data from Lipid Research Clinics study participants at visit 2 (3972 and 2346 adult men and women), we examined the hypothesis that parental mortality from cardiovascular disease (CVD) or cancer before age 60 predicts their adult progeny's lipid and lipoprotein levels. Weighted regression analysis was used to control for the potential effect of progeny's other CVD risk factors (age, systolic blood pressure, Quetelet index, cigarette smoking, and alcohol consumption), and to assess for the effect of progeny's parental cause-specific mortality status on progeny's lipids and lipoproteins. Nearly all of the statistically significant parent-progeny predictions were for sons. Paternal death from CVD before age 60 years was associated with significantly higher plasma total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels in sons and (at marginal significance) in daughters, when compared with those in reference progeny with paternal survival over age 60 or over age 75. Maternal death from CVD before 60 was associated with lower levels of high-density lipoprotein cholesterol (HDL-C) in sons. Paternal and maternal death from cancer before age 60 years were associated with higher triglyceride levels in adult sons than in sons whose parents had lived beyond ages 60 and 75. Paternal all-cause mortality before age 60 was associated with higher cholesterol and triglycerides in sons; maternal all-cause mortality before age 60 was associated with depression of HDL-C in sons. Familial aggregation of lipids and lipoproteins may account, in part, for familial aggregation of CVD. Knowledge of family history facilitates identification of progeny at higher risk for CVD by virtue of elevated cholesterol or LDL-C, or reduced HDL-C.

Adult↗
PubMed1985

Marrow transplantation from related donors other than HLA-identical siblings.

Marrow transplantation has generally been limited to patients with a sibling who is genotypically identical for HLA. In a study of the acceptable limits of HLA incompatibility, 105 consecutive patients with hematologic cancers who received marrow grafts from haploidentical donors (study group) were compared with 728 similar patients concurrently receiving grafts from HLA genotypically identical siblings (control group). The unshared haplotypes differed variably: 12 were phenotypically but not genotypically identical for HLA-A, HLA-B, and HLA-D; 63 differed at one locus (A, B, or D); 24 at two loci; and 6 at three. A higher proportion of study patients had delayed engraftment, granulocytopenia, or graft rejection. Acute graft versus host disease occurred earlier and with greater frequency in study patients. The risk of the disease did not correlate with disparity for Class I (A or B) versus Class II (D-region) loci. Thus, incompatibility for HLA has an important effect on the course after clinical marrow transplantation. In spite of these complications, there was no statistically significant difference in the survival of the study patients and control patients who received their transplants during remission.

Acute Disease↗
PubMed1985

Phospholipids, sterol carrier protein2 and adrenal steroidogenesis.

Rat adrenocortical cells and preparations of plasma membrane and mitochondria have been employed to assess the effects of phospholipids and of sterol carrier protein2 (SCP2) on specific aspects of adrenal steroidogenesis. With intact cells, liposomal dispersions of cardiolipin caused significant stimulation of corticosterone output, while preparations of phosphatidylcholine, phosphatidylinositol, or the 4'-phosphate and the 4',5'-diphosphate derivatives of phosphatidylinositol were without effect. With the adrenal plasma membrane preparation, none of the added phospholipids affected either sodium fluoride or ACTH-responsive adenylate cyclase activity. With intact mitochondria, only cardiolipin, among the various phospholipids, tested, caused a concentration-dependent stimulation of pregnenolone production. However, even at the highest concentration of cardiolipin tested (500 microM), the stimulatory effect was only half that observed with 0.7 microM SCP2, and the two effectors were not synergistic. SCP2 caused a redistribution of cholesterol from mitochondrial outer to inner membranes, while cardiolipin, which is an activator of cytochrome P-450scc, had no effect on distribution of mitochondrial membrane cholesterol.

Adrenal Cortex↗
PubMed1985

Marrow transplant experience in children with acute lymphoblastic leukemia: an analysis of factors associated with survival, relapse, and graft-versus-host disease.

One hundred fourteen children with acute lymphoblastic leukemia were treated with allogeneic marrow transplantation from HLA-identical siblings after conditioning with cyclophosphamide and total body irradiation. Methotrexate was given posttransplantation for prophylaxis of graft-versus-host disease. The minimum follow-up after transplantation was 2 years. Sixteen of 51 patients transplanted in marrow remission survive from 2.1 to 8.9 years (median 2.7), 13 in continuous remission, one in remission following testicular relapse, and two after marrow relapse. Sixty-three were transplanted in relapse and eight survived 3-10 years (median 5.7), five in continuous remission, and three in remission following testicular relapse. In a multivariate analysis, factors significantly related to increased survival were marrow remission at transplant (p less than 0.007) and chronic graft-versus-host disease (p less than 0.005). Factors associated with increased relapse were marrow relapse at transplant (p less than 0.002) and absence of significant graft-versus-host disease (p less than 0.004). The development of acute graft-versus-host disease was associated with high marrow cell doses (p less than 0.04). These data suggest that some children with acute lymphoblastic leukemia and a poor prognosis with conventional chemotherapy may be cured with marrow transplantation.

Adolescent↗
PubMed1985

Treatment of acute graft-versus-host disease after allogeneic marrow transplantation. Randomized study comparing corticosteroids and cyclosporine.

Seventy-seven patients (age 12 to 46 years) who underwent allogeneic marrow transplantation for hematologic malignancy or aplastic anemia and who had grade II to IV acute graft-versus-host disease despite methotrexate prophylaxis were randomly assigned to receive methylprednisolone 2 mg/kg per day intravenously (n = 39) or cyclosporine (n = 38) either 12 to 15 mg/kg per day orally or 3 to 5 mg/kg per day intravenously. In both groups, clinical and histologic evidence of graft-versus-host disease was detected at medians of 16 and 25 days, respectively. Drugs were given for a minimum of 14 days unless significant deterioration occurred. If graft-versus-host disease did not improve with this therapy, treatment with a second agent was initiated. Treatment responses were scored after reviewing clinical and laboratory data collected before, during, and after the 14-day treatment period. Possible scores were as follows: -1, worse; 0, no change; + 1, improvement in one organ system (skin, liver, gut) with no deterioration in the other two; +2, complete resolution of all involved systems. The median response score among 39 methylprednisolone-treated patients was 0. Sixteen patients (41 percent) showed response to treatment, 11 with partial and five with complete response. The median response score among 38 cyclosporine-treated patients was +1. Twenty-three patients (61 percent) showed response to treatment, 15 with partial and eight with complete response (p = 0.039). Twenty patients receiving methylprednisolone and 18 receiving cyclosporine required additional therapy. The incidence of chronic graft-versus-host disease was similar in both groups. It developed in all nonresponding patients at risk who had received secondary therapy. Among responding patients (scores +1 or +2) who were not given additional treatment, chronic graft-versus-host disease developed in eight of 11 (72 percent) receiving methylprednisolone and five of ten (50 percent) receiving cyclosporine. Survival beyond 17 months was similar in the two groups (28 percent and 24 percent, respectively). These data suggest that cyclosporine is a useful agent for the treatment of acute graft-versus-host disease, comparable in its efficacy to methylprednisolone.

Acute Disease↗
PubMed1985

Allogeneic marrow transplantation in the treatment of MOPP-resistant Hodgkin's disease.

Eight patients with disseminated Hodgkin's disease resistant to MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) chemotherapy were treated with high-dose chemoradiotherapy and marrow transplantation from an HLA-identical sibling. Two patients remain alive in unmaintained complete remission (CR) at 38 and 39 months after transplant. In the other six patients, reasons for failure included relapse of lymphoma (two patients), or death due to complications of the transplant procedure, including Legionnaire's disease, disseminated zoster, graft-v-host disease, and aspiration pneumonia secondary to severe mucositis. These results demonstrate that some patients with MOPP-resistant Hodgkin's disease can obtain prolonged CR following intensive chemoradiotherapy and allogeneic marrow transplantation.

Adult↗
PubMed1985

Autologous marrow transplantation in patients with acute nonlymphocytic leukemia in first remission.

Thirteen patients with acute nonlymphocytic leukemia underwent autologous bone marrow transplantation (ABMT) following high doses of cyclophosphamide and total body irradiation while in first complete remission. After marrow infusion four patients received human leukocyte interferon and nine received intravenous methotrexate. One patient died on day 16 of septicemia associated with severe gastrointestinal toxicity. In the remaining 12 patients the median day of achieving a circulating granulocyte level of 500/mm3 was 29 (range 15-94 days). Eight of 12 evaluable patients achieved a sustained platelet count of 20,000/mm3 or greater in a median of 44 days (range 12-116 days) and four patients did not achieve this level before death on days 116-396. One patient died on day 116 of interstitial pneumonitis secondary to cytomegalovirus. Eight patients relapsed 58-365 days after AMBT (median 335 days), and all have died. Three patients are alive and well without relapse 26-50 months after ABMT. This study demonstrated that poor engraftment was a frequent complication of ABMT when early posttransplant cytotoxic therapy was attempted. Relapse of leukemia and the number of long-term survivors in this small group of patients was not different from that expected following conventional therapy.

Acute Disease↗
PubMed1985

Effects of in vitro depletion of T cells in HLA-identical allogeneic marrow grafts.

We report results of a pilot study designed to evaluate the effects of in vitro depletion of T lymphocytes from donor marrow in patients receiving HLA-identical marrow grafts for treatment of hematologic malignancies. Twenty patients aged 31 to 50 years were prepared for transplantation with cyclophosphamide (120 mg/kg) and fractionated total body irradiation (12.0 or 15.75 Gy). All received cyclosporine after grafting. The donor marrows were treated with a mixture of eight murine monoclonal antibodies and rabbit serum complement in a manner that achieved a 2- to 3-log depletion of T cells in most patients. Initial engraftment occurred promptly in 19 of the patients, and only three had clinically significant acute graft-versus-host disease. Depletion of donor T cells, however, was associated with an increased incidence of graft failure, which occurred as late as 244 days after transplantation. Graft failure was transient in one patient but apparently was irreversible in seven others. Three of the seven patients had cytogenetic but not morphological evidence of leukemic relapse at the time of graft failure. All seven patients with irreversible graft failure have died, six after receiving second bone marrow transplants. Seven of the eight cases of graft failure occurred among the 11 patients prepared for transplantation with 12.0 Gy of total-body irradiation, and only one occurred among the nine patients with advanced malignancies who received 15.75 Gy of total-body irradiation. This association with irradiation dose suggests that host factors were partly responsible for the graft failures. Because graft failure seldom occurs in irradiated recipients of unmodified HLA-identical allogeneic marrow transplants, it appears that T cells in the donor marrow may serve a beneficial function in helping to maintain sustained engraftment possibly by eliminating host cells that can cause graft failure. Optimal application of in vitro manipulation of donor marrow as a method for preventing graft-versus-host disease will require more effective immunosuppression of the recipient in order to assure sustained engraftment and function of donor stem cells.

Adult↗
PubMed1984

Prophylaxis of infection in patients with aplastic anemia receiving allogeneic marrow transplants.

One hundred one patients with severe aplastic anemia underwent allogeneic marrow transplantation and received one of three forms of infection prophylaxis: oral nonabsorbable antibiotics and isolation and decontamination in a laminar airflow room (36 patients); prophylactic granulocyte transfusions from a single family member donor (33 patients); or conventional treatment in single rooms with hand-washing and mask precautions (31 patients). During the period of granulocytopenia, patients in the laminar airflow rooms acquired fewer infections than either of the other groups, but this difference was statistically significant only when compared with the group receiving conventional treatment. Patients in the laminar airflow rooms had significantly fewer infections after engraftment as compared with the other two groups. Incidence of interstitial pneumonia and graft rejection was not different among the three groups. Acute graft-versus-host disease occurred later (Day 47) in the group in the laminar airflow rooms as compared with the group receiving prophylactic granulocyte transfusions (Day 23) or the group receiving conventional treatment (Day 20). The incidence of grades II to IV acute graft-versus-host disease was less in the patients in the laminar airflow rooms but only reached borderline significance (p = 0.08) when compared with the conventionally treated patients. The survival at Day 100 was 92 percent for the group in the laminar airflow rooms, 79 percent for the group receiving prophylactic granulocyte transfusions, and 64 percent for the group receiving conventional treatment.

Adolescent↗
PubMed1984

Posture in labour: patients' choice and its effect on performance.

In a study to assess the influence of maternal posture on the progress and efficiency of labour, 275 parturients were asked to choose between remaining in bed during labour or being ambulant. Among primigravidae in spontaneous labour those who remained ambulant throughout had the shortest labours; they also had shorter labours than others who were only partially ambulant. Analysis of the data, based on original preference, however, suggests that an easy labour allows ambulation rather than vice versa. Radiotelemetry was used to transmit the fetal heart signal in all ambulant patients and provided satisfactory fetal surveillance in both high- and low-risk labours.

Female↗
PubMed1984

Allogeneic marrow transplantation in the treatment of preleukemia.

Ten patients with preleukemia and life-threatening pancytopenia were treated with marrow transplantation. In all ten cases allogeneic marrow was successfully engrafted. In three patients prepared for transplantation with cyclophosphamide alone, the abnormal cell clone either persisted or reemerged within 6 months of transplantation. The other seven patients were treated with cyclophosphamide plus total body irradiation before transplantation and six of the seven are alive and well without evidence of disease from 7 to 25 months after transplantation. These results suggest that cyclophosphamide alone before marrow transplantation is incapable of eradicating the abnormal clone. Cyclophosphamide combined with total body irradiation appears more effective, although more time is needed for full evaluation of results. This experience also emphasizes the importance of performing chromosome studies before transplantation for pancytopenic states in order to identify cases of preleukemia.

Adolescent↗
PubMed1984

Marrow harvesting from normal donors.

The experience at a single institution in harvesting marrow for allogeneic transplantation on 1,270 occasions from 1,160 normal donors is presented in detail, together with an analysis of all the donor complications. Four donors were less than 2 years old, and the youngest was 6 1/2 months. No special difficulties were encountered with these young donors. Hospitalization time was three days or less for 99% of the procedures. Six donors had life-threatening complications; three of a cardiopulmonary and two of an infectious nature, and one cerebrovascular embolic episode. Significant operative site morbidity, usually transient neuropathies, occurred in ten procedures. Ten percent of the donations were associated with transient postoperative fever of unknown origin. Increasing donor age was associated with a reduction of the cellularity of the marrow harvest. The use of stored autologous blood permitted the avoidance of blood bank transfusion in 81% of males, 69% of females, and 50% of children. It was concluded that the procedure was associated with a very low risk of complication, but that the involvement of normal donors in such an operation justifies stringent monitoring.

Adolescent↗
PubMed1983

A randomised trial to evaluate the use of a birth chair for delivery.

A randomised study of 189 deliveries was conducted to compare performance in the conventional dorsal position with that in a birth chair. There was no significant difference in the length of the second stage of labour, the time spent bearing down, or the need for operative delivery. Overall blood-loss was greater among patients delivered in the chair but more of this group had either an intact perineum or only superficial damage. The condition of the neonates in the two delivery groups was similar.

Clinical Trials as Topic↗
PubMed1983

Factors associated with graft rejection after HLA-identical marrow transplantation for aplastic anaemia.

One hundred and seventy-five consecutive patients with severe aplastic anaemia were given high-dose cyclophosphamide followed by marrow grafts from healthy, HLA-identical family members, and 168 lived long enough to show engraftment. In 38 patients the graft was rejected and 29 of these died. This analysis, using a binary logistic regression model, was aimed at identifying factors that predicted marrow graft rejection. Five factors correlated with graft rejection: (1) previous blood transfusion; (2) a positive relative response in mixed leucocyte culture indicating sensitization of patient against donor; (3) a low number of marrow cells used for transplantation; (4) marrow grafts from male donors; and (5) lack of infusion of viable donor buffy coat cells in addition to the marrow for transfused patients. The findings confirm the importance of transplanting early before transfusion and indicate that the greatest possible amount of donor marrow (supplemented by stem cells/lymphoid cells derived from the peripheral blood) should be obtained.

Anemia, Aplastic↗