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Biomedical subjects

S Myers

Publications and source records attributed to S Myers.

At least 55 records · Page 3Linked to original sources
PubMed1995

Apolipoprotein A-I stimulates placental lactogen expression by human trophoblast cells.

Earlier studies from our laboratory indicated that apolipoprotein A-I (Apo A-I) stimulates the acute release of human placental lactogen (hPL) from trophoblast cells in culture. We have now demonstrated that Apo A-I also causes a secondary increase in hPL release, beginning about 6 h after exposure to Apo A-I, that is blocked by cycloheximide and actinomycin D. Apo A-I also stimulated a dose-dependent increase in hPL promoter activity in JAR cells transfected with a 1.1-kilobase (-1078/2) fragment of the hPL3 promoter coupled to a chloramphenicol acetyltransferase (CAT) reporter gene. Maximal stimulation, 5.2-fold above basal levels, occurred at an Apo A-I concentration of 1.5 mg/ml, which is within the physiological concentration of Apo A-I during pregnancy. 37pA, a synthetic amphipathic peptide that mimics the secondary structure of Apo A-I and stimulates the synthesis and release of hPL, also stimulated a dose-dependent increase in CAT activity, with maximal stimulation comparable to that caused by Apo A-I. In addition, Apo A-I stimulated a modest increase in CAT activity in BeWo choriocarcinoma cells, Chinese hamster ovary cells, and HeLa cells. However, the maximal stimulation of hPL promoter activity in the Chinese hamster ovary and HeLa cells (approximately 2.5-fold above basal levels) was less than that in choriocarcinoma cells, suggesting that trophoblast cell nuclear factors may be necessary for maximal expression of the promoter in response to Apo A-I. Taken together, these results indicate that Apo A-I stimulates hPL gene expression, and that DNA elements in the first 1.1 kilobase of the promoter are sufficient for transactivation by Apo A-I.

Animals↗
PubMed1995

Source of stem cells impacts on hematopoietic recovery after high-dose chemotherapy.

The restoration of hematopoiesis after high-dose chemotherapy may be accelerated by the use of stem cells from the bone marrow (BM) or peripheral blood. Numerous reports utilizing mobilized peripheral blood progenitor cells (PBPC) for stem cell rescue have shown that PBPC are sufficient to restore hematopoiesis, but there are little data comparing the recovery among patients treated with various stem cell sources. We reviewed the clinical outcomes of 69 women at our institution who were treated for locally advanced or metastatic breast cancer with high-dose cyclophosphamide (CY) and thiotepa and autologous stem cell and growth factor support. Of the 43 patients with normal BM, 19 received BM alone and 24 received BM plus G-CSF mobilized PBPC. Of the 26 patients with evidence of metastatic disease in the BM, or evidence of fibrosis and hypocellularity, 15 received CY-mobilized PBPC and 11 received CY/G-CSF-mobilized PBPC. Of the marrow-negative patients, those receiving BM alone had significantly longer (P < 0.001) granulocyte recovery (absolute neutrophil count > 500 x 10(6)/l) and platelet recovery (platelets > 50 x 10(9)/l) compared with BM + G-CSF-mobilized PBPC. They also had significantly longer (P < 0.001) durations of antibiotic and amphotericin usage, increased transfusion requirements and longer hospitalizations. Of the marrow-positive patients, there was a slightly shortened granulocyte recovery, shortened hospital stays and lessened amphotericin usage in the patients who received CY/G-CSF-mobilized PBPC compared with the CY-mobilized patients. Although the number of harvested mononuclear cells differed significantly between the groups, this did not correlate with the time to hematopoietic recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

The cost of intensive care: a comparison on one unit between 1988 and 1991.

OBJECTIVE: To assess the changes in cost of intensive care in one unit after a 3 year period and to evaluate the relative costs of an integrated high dependency unit. DESIGN: Combined retrospective and prospective audit of all expenditure incurred in an intensive care/high dependency unit over two periods: April 1988-February 1989 and January-July 1991. SETTING: Combined 13-bedded intensive care/high dependency unit of a central London teaching hospital. RESULTS: The overall cost rose by 50%. Hidden costs such as infrastructure maintenance, capital assets, pathology and radiology services accounted for nearly a quarter of total expenditure. Pharmacy and supplies each accounted for some 10% of total expenditure whereas staff costs exceeded 50%. The cost of the intensive care section rose by 14% of 1149 pounds per patient day as increased bed occupancy offset increases in nurse: patient ratios and expenditure on consumables. However, the cost of the high dependency unit section rose by 87% to 437.83 pounds. This was due to a lower bed occupancy (through increased patient turnover), improved staffing ratios, and increased utilisation of equipment and supplies. CONCLUSIONS: Intensive care is an increasingly expensive speciality, the costs for which are rising over and above the rate of general inflation. Staff costs are by far the largest single item of expenditure. Large reductions in spending on drugs and consumables are unlikely to provide considerable savings on the total budget. Hidden costs account for a high proportion of the budget and should be taken into account when evaluating cost. The significantly lower cost of high dependency care should encourage studies into its cost-effectiveness.

Health Services Research↗
PubMed1994

Benchmarking: finding ways to improve.

BACKGROUND: This article provides health care organizations with a benchmarking methodology to use in comparing practices and processes to identify and actualize opportunities for improvement. The 15-step model can be used to guide internal and external benchmarking activities in a variety of health care settings. EXAMPLES: Two internal benchmarking case studies are illustrated: (1) one hospital used the Baxter model to evaluate its laparoscopic cholecystectomy services, and (2) another prepared for expansion of cardiac catheterization services. CONCLUSIONS: Two key factors of a successful benchmarking initiative are highlighted: management commitment and involvement, and the need to understand internal practices and processes before benchmarking.

Cholecystectomy, Laparoscopic↗
PubMed1993

Accuracy of diagnosis of psychosis on general practice computer system.

OBJECTIVES: To determine the accuracy of diagnoses of schizophrenia and non-affective psychosis entered by general practitioners on a computer system. To compare recording of clinical events on computer with written records. DESIGN: Examination of case notes of all patients with a computer diagnosis of psychosis. Search of 8000 randomly selected patient records to identify patients with psychosis not recorded on computer and comparison of 141 computer and written entries for prescribing and consultation in each practice. SETTING: 13 London practices on the VAMP research bank. MAIN OUTCOME MEASURES: Accuracy of record of psychosis compared with ICD 9, American Psychiatric Association diagnostic manual, and syndrome checklist criteria. RESULTS: Computer search revealed 102 patients with schizophrenia, 78 with other psychoses, and 71 with non-affective psychosis who had adequate case notes. The sensitivity and positive predictive value of the computer diagnosis of schizophrenia were 88% (95% confidence interval 62% to 98%) and 71% (48% to 88%). For all non-organic psychoses sensitivity was 91% (74% to 97%) and positive predictive value was 91% (74% to 98%). On average 95% of all known prescriptions and 74% of all consultations were recorded on computer compared with 42% and 75% in written records. CONCLUSIONS: Recording of psychotic illness on the VAMP computer is accurate and complete. Prescribing was more fully recorded on the computer than on the written records. Computer databases of well motivated general practitioners could be used for research.

Ambulatory Care Information Systems↗
PubMed1993

New strategies in marrow purging for breast cancer patients receiving high-dose chemotherapy with autologous bone marrow transplantation.

High-dose chemotherapy and autologous bone marrow transplantation (ABMT) are commonly used to treat selected patients with high-risk breast cancer. A limitation of ABMT is that clonogenic cancer cells could be collected with the bone marrow and produce a relapse of diseases when reinfused into patients. Purging the marrow ex vivo may eliminate the tumor cells, but it can also delay engraftment. We employed two different purging methods whereby breast cancer cells were depleted without delaying engraftment. The addition of WR-2721 (amifostine) to 4-hydroperoxycyclophosphamide (4-HC) reduced the time to engraftment by 10 days compared with marrow purged with 4-HC alone (26 versus 37 days, respectively). The positive selection of CD34+ hematopoietic progenitors produced engraftment within 21 days. The use of granulocyte colony-stimulating factor (G-CSF) accelerated the engraftment time of CD34+ hematopoietic progenitors to 11 days.

Amifostine↗
PubMed1993

The role of prostaglandin I2 and biliary lipids during evolving cholecystitis in the rabbit.

BACKGROUND: Acute cholecystitis increases gallbladder prostanoid synthesis. The percent study examined the hypothesis that increased endogenous gallbladder release of prostaglandin I2 (PGI2) after bile duct ligation is caused by both increased ductal pressure and altered biliary lipids. METHODS: Prostanoid release, biliary lipids, and in vitro fluid absorption of sham gallbladders were compared with those of gallbladders in which acute cholecystitis was induced after common bile duct ligation for 6, 24, and 72 hours. RESULTS: Bile duct ligation for 6, 24, and 72 hours increased gallbladder PGI2 release twofold and increased gallbladder bile levels of lysolecithin and taurine-conjugated bile acids fivefold compared with sham groups (P < 0.05). In vitro gallbladder fluid absorption was decreased by 50% or more in the 6-, 24-, and 72-hour bile duct-ligated groups (P < 0.05) but was reversed by indomethacin only in the 6-hour ligated group. CONCLUSIONS: Decreased gallbladder fluid absorption following bile duct ligation for 6 hours was caused by increased gallbladder release of PGI2. Decreased gallbladder fluid absorption following bile duct ligation for 24 and 72 hours was not a prostanoid-mediated process (not reversed by indomethacin) but was associated with increased bile levels of proinflammatory biliary lipids.

Absorption↗
PubMed1993

Solid-state emulsions: the effects of process and storage conditions.

The effects of process and storage conditions of solid-state emulsions were studied. Oil-in-water emulsions may be prepared from solid state emulsions by adding an aqueous phase to the solid. Solid-state emulsions are prepared by processing an oil phase and an aqueous solution of matrix material via a solvent removal process. Sucrose, the carrier material utilized in this report, results in a metastable solid or glass, which can transform upon aging to a more stable thermodynamic state. Aging was determined by monitoring the crystallinity as a function of time, temperature, relative humidity, and grinding. The crystallinity of solid-state emulsions was determined with X-ray diffraction and differential scanning calorimetry. Results indicate that solid-state emulsions should be stored between 15 and 25% relative humidity at 25 degrees C. Grinding has no apparent effect on the crystallinity of the sample, as detected by X-ray diffraction, although the microcrystallinity is increased. The utilization of silinized glassware enabled the sample-to-sample microcrystalline variability to be reduced.

Calorimetry, Differential Scanning↗
PubMed1992

Increased gall-bladder prostanoid synthesis after bile-duct ligation in the rabbit is secondary to new enzyme formation.

Ligation of the common bile duct (BDL) in the male rabbit resulted in increased gall-bladder microsomal total cyclo-oxygenase activity with prostaglandin E2 (PGE2) and 6-oxoprostaglandin F1 alpha [6-oxo-PGF1 alpha, stable metabolite of prostaglandin I2 (PGI2; prostacyclin)] as the major prostanoids synthesized after 24 and 72 h. Kinetic analysis of gallbladder microsomal membrane fractions incubated with increasing levels of [14C]arachidonic acid indicated that BDL for 24 and 72 h did not change substrate affinity (apparent Km) but markedly increased the rate of conversion (apparent Vmax.) suggesting the presence of more total enzyme responsible for synthesis of 6-oxo-PGF1 alpha and PGE2. BDL for 24 and 72 h significantly increased gall-bladder tissue slice basal release of 6-oxo-PGF1 alpha, but not PGE2, when compared with the controls. Gall-bladder slice release of PGE2 was 3-fold less than 6-oxo-PGF1 alpha in the control gall-bladder slices. Immunoblot analysis of 72 h BDL gall-bladder microsomal membrane fractions showed a slight increase in cyclo-oxygenase content and a 5-fold increase in the content of prostacyclin synthase as compared with the control. These data suggest that the BDL-stimulated total gall-bladder cyclo-oxygenase activity was the result of an increase in the level of specific prostaglandin-synthetic enzymes, in particular prostacyclin synthase, and not from a change in enzyme affinity.

Animals↗
PubMed1992

Treatment of hypercholesterolemia: comparison of younger versus older patients using wax-matrix sustained-release niacin.

OBJECTIVE: Compare lipid response, side effect profile and toxicity of younger (less than 50 years) versus older (50 to 70 years) hypercholesterolemic subjects taking wax-matrix sustained-release niacin (Endur-acin). STUDY DESIGN: An 8-week randomized double-blind placebo controlled trial. SETTING: General community. PARTICIPANTS: Volunteers from community cholesterol screening programs and chart review of patients at family practice clinics. Male and female subjects, age 20 to 70, with baseline low density lipoprotein cholesterol level within the 75th to 95th percentile, excluded if on medications that affect lipids or if a history of diabetes, gout, peptic disease, or liver disease is present. INTERVENTION: Nicotinic acid dosage schedules were 1,000 mg/day, 1,250 mg/day, 1,500 mg/day, or 2,000 mg/day for 8 weeks. MAIN OUTCOME MEASURES: Change in blood lipids and blood chemistries, side effects, and pill compliance. RESULTS: 158 subjects (79%) completed the study. Higher dose groups (1,500 mg and 2,000 mg) demonstrated improvements in total cholesterol, LDL-cholesterol, HDL cholesterol, and total-to-HDL-cholesterol ratio (P less than 0.05) compared to baseline and controls. Higher-dose older subjects demonstrated significantly greater improvements than younger subjects on comparable doses for total cholesterol, HDL cholesterol, total-to-HDL-cholesterol ratio, and triglycerides, P less than 0.02). Adherence to medication schedules was better and incidence of side effects and toxicity no greater in older subjects compared to younger. CONCLUSION: Wax-matrix niacin (Endur-acin) was shown to be effective and well tolerated for the pharmacological treatment of hypercholesterolemia. Older persons, ages 50 to 70, appear to experience greater benefits with no greater side effects when compared to younger subjects on similar doses.

Adult↗
PubMed1992

Characterization of chemotherapy mobilized peripheral blood progenitor cells for use in autologous stem cell transplantation.

Twenty patients were treated with chemotherapy to mobilize progenitors into the blood. Peripheral blood stem cells were quantitated in peripheral blood or leukapheresis products using colony assays and flow cytometric measurement of CD34+ cells. In four patients where complete sets of serial samples were obtained, the appearance of CD34+ cells preceded the increase in CFU-GM by 24-48 h. Peak levels of CD34+ cells ranged from 0.6-5% and coincided with the peak increase in CFU-GM. Mobilized CD34+ cells contained subsets expressing CD33, CD13, CD45RA, CD38, HLA-DR, CD61 and CD41. Subsets of CD34+ cells expressing CD33, CD13, or CD45RA represent committed myeloid progenitors. In contrast to bone marrow CD34+ cells, few mobilized CD34+ cells expressed CD71, CD7, CD19 or CD10. Prompt engraftment of granulocytes greater than 500 x 10(6)/l at a median of 13 days and platelets greater than 50 x 10(9)/l at a median of 15 days was observed in patients reconstituted with mobilized cells. These data indicate that CD34+ cells mobilized during recovery from chemotherapy are predominantly myeloid in phenotype and contain few actively proliferating cells or cells with lymphoid phenotypes.

Antigens, CD↗
PubMed1992

Phase I study of busulfan, cyclophosphamide, and timed sequential escalating doses of cytarabine followed by bone marrow transplantation.

In both animal models and human studies in leukemia, residual disease on day 8 following myelosuppressive therapy is in a proliferative phase and therefore may be sensitive to the S-phase specific drug cytarabine. Based on this concept, 17 patients with refractory or relapsed leukemia or lymphoma undergoing either autologous or allogeneic bone marrow transplantation (BMT) were treated on a Phase I protocol using high doses of busulfan (16 mg/kg, days -10, -9, -8, -7) and cyclophosphamide (120 mg/kg, days -6, -5) followed by escalating doses of a 48-h continuous infusion of cytarabine (starting dose 1000 mg/m2/48 h, days -3, -2). Ten patients received autologous transplants (two with Hodgkin's disease, seven with non-Hodgkin's lymphoma, one with chronic myelogenous leukemia (CML) in blast phase). Seven received allogeneic BMT (two with refractory acute myelocytic leukemia (AML), one with refractory acute lymphoblastic leukemia (ALL) undergoing a second BMT, one with Burkitt's-type leukemia, one with ALL in fifth relapse and two with CML in accelerated/blast phase). Two of these patients received a T cell-depleted haploidentical transplant. The maximum tolerated dose of cytarabine was 1500 mg/m2/48 h; a pulmonary syndrome including dyspnea, hypoxemia, and interstitial infiltrates which responded to aggressive diuresis was the dose limiting toxicity. Of the 10 patients who received cytarabine doses of 2000 or 2500 mg/m2/48 h, five patients developed adult respiratory distress syndrome (ARDS) with three patients requiring intubation; two recovered. Of the nine patients with lymphoma, seven responded with complete tumor clearance (CTC) with two patients tumor-free 13 and 15 months post-BMT, one remained refractory and one died too early to evaluate (TETE).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Niacin revisited. A randomized, controlled trial of wax-matrix sustained-release niacin in hypercholesterolemia.

Two hundred one male and female subjects, aged 20 to 70 years, with elevated low-density lipoprotein cholesterol values (in the 75th to 95th percentiles), participated in a randomized, controlled, double-blind study using a new form of niacin (Enduracin), which employs a wax-matrix vehicle for sustained release. Four niacin treatment groups (daily doses of 2000, 1500, 1250, and 1000 mg) were compared with placebo- and diet-treated controls to determine side-effect profile and optimal range of efficacy. The groups given 2000 and 1500 mg demonstrated significant reductions in values of low-density lipoprotein cholesterol (-26% and -19.3%, respectively), total cholesterol (-18.4% and -13.3%), and total cholesterol-high-density lipoprotein cholesterol ratio (-20.4% and -19.4%) when compared with diet- and placebo-treated controls. Smaller improvements were seen in high-density lipoprotein cholesterol and triglyceride levels. Blood chemistry monitoring indicated that reduction in low-density lipoprotein cholesterol level strongly correlated with an increase in baseline levels of some enzymes for niacin-treated subjects. The improved side-effect profile of the wax-matrix form of niacin was particularly notable. The dropout rate due to side effects was only 3.4% and was coupled with good medication compliance.

Adult↗
PubMed1991

Inhibition of anaphylaxis-evoked intestinal fluid secretion by the dual application of an H1 antagonist and cyclooxygenase inhibitor.

The regulation of anaphylaxis-mediated fluid secretion by the small intestine was examined in rats immunized by infection with Trichinella spiralis and reinfected by intraduodenal injection with L1 larvae. Net fluid secretion, which was measured as the volume of fluid present in the intestine 30 minutes after the challenge infection, was significantly greater in both actively and passively immunized rats than in nonimmune rats. The amount of fluid recovered from the immune host was equivalent to that secreted in response to 50 micrograms/kg of prostaglandin E2 or 250 micrograms/kg of cholera toxin. Worm-induced fluid secretion in immune hosts was reduced by treatment with diphenhydramine and inhibited by the dual application of diphenhydramine and indomethacin. Indomethacin alone had no effect despite inhibiting mucosal prostaglandin synthesis. Fluid secretion was unaltered by prior treatment of immune rats with a 5-lipoxygenase inhibitor, L-651,392, and only slightly reduced when L-651,392 was used in combination with indomethacin. After a challenge infection, more histamine was released into intestinal loops of immune rats than those of nonimmune rats. Prechallenge treatment of immune rats with indomethacin caused a twofold increase in histamine release. In summary, anaphylaxis-induced fluid secretion in the small intestine is mediated largely by histamine and cyclooxygenase products. This secretion can be lowered by treatment with diphenhydramine and further reduced by diphenhydramine in combination with indomethacin. The paradoxical effects of indomethacin when used alone and in combination with diphenhydramine are explained by the downregulation of histamine release by products of the cyclooxygenase pathway.

Analysis of Variance↗