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Biomedical subjects

S Myers

Publications and source records attributed to S Myers.

At least 19 recordsLinked to original sources
PubMed1995

Octreotide does not prevent bacterial translocation in an infant piglet model of intestinal ischemia-reperfusion.

The process of bacterial translocation (BT) after ischemia/reperfusion (I/R) injury is reported to be mediated by local mucosal factors, the effects of pancreatic enzymes, epithelial disruption, and by dysfunctional intestinal motility. Octreotide (OCT), a somatostatin analog, has been postulated to protect against BT by influencing one or more of these factors. Twenty-two formula-fed piglets (weight, 3.5 +/- 0.5 kg; age, 20 +/- 5 days) were divided into four groups: control (no drug given; no I/R; n = 6), I/R (no drug given; n = 5), I/R plus low-dose OCT (LD OCT, 0.08 microgram/kg; n = 6), and I/R plus high-dose OCT (HD OCT, 8 micrograms/kg; n = 5). All experimental subjects had nonocclusive mesenteric ischemia induced by reversible pericardial tamponade with mesenteric flow decreased to 25 +/- 5% of baseline for 5 hours followed by 15 +/- 5 hours of reperfusion. Mesenteric lymph nodes (MLN), liver, spleen, blood, and peritoneum were harvested for blind microbial analysis. None of the animals in the control group experienced translocation to the tissues tested. All of the animals in the I/R group experienced BT to the MLN. The subjects in the LD OCT and HD OCT groups experienced BT to the MLN 66% and 80% of the time, respectively. Despite the reported clinical evidence that OCT can protect the intestinal mucosa from injury and increase the clearance of bacteria from the gastrointestinal tract, in this study in which variables other than I/R known to promote bacterial translocation were eliminated, OCT failed to modify or prevent the occurrence of translocation to the MLN after I/R injury.

Animals↗
PubMed1995

Transplantation of keratinocytes in the treatment of wounds.

BACKGROUND: Keratinocyte grafting can be used to treat acute traumatic and chronic non-healing wounds. The keratinocyte sheets are fragile and clinical "take" is difficult to assess, especially as activated keratinocytes secrete many growth factors, which have effects on wound healing apart from take. We have developed animal models of grafting that allow us to examine factors influencing autologous keratinocyte graft take. Results show clearly that pretreatment of the wound bed with viable dermis greatly increases the take of keratinocyte grafts. DATA SOURCES: International literature. CONCLUSIONS: As a greater understanding of the complex interactions of cell and matrix evolve, so will potential therapeutic maneuvers, not just in the field of cultured keratinocyte grafts, but clearly in that of benign tumors, for example, keloids, and that of oncology. There is now overwhelming evidence of the requirement for a dermal substitute for cultured keratinocyte autografts, and the sheet complexity of the situation demands that this should approximate live human dermis as closely as possible. The stumbling blocks relate to avoiding the risks of viral transmission, tissue matching of host and donor, providing early epithelial cover, and improving delivery systems for fragile keratinocyte grafts.

Animals↗
PubMed1995

Evaluation of the clinical usefulness of thermodilution volumetric catheters.

OBJECTIVE: To determine if treatment modalities (fluid, inotropes, and blood) would be altered based on preload measurements of right ventricular end-diastolic volume index measured by fast response thermodilution catheter, as compared with pulmonary artery occlusion pressure (PAOP). DESIGN: A prospective clinical trial. SETTING: An 11-bed surgical intensive care unit (ICU) at The Queen's Medical Center, an affiliate of the University of Hawaii Surgical Residency program. PATIENTS: Surgical ICU patients who required pulmonary artery catheters, except those patients with arrhythmias or history of tricuspid valve disease. INTERVENTIONS: During the first 48 hrs after catheter insertion, hemodynamic data were obtained at least every 4 hrs. Treatment of low preload was initiated only if clinical indications were present. These indications included a mean arterial pressure of < 70 mm Hg, heart rate of > 120 beats/min, urine output of < 40 mL/hr, stroke volume of < 40 mL/m2 with oxygen delivery of < 450 mL/min/m2, and lactic acidosis. Volume infusion was considered if PAOP was < 18 mm Hg and right ventricular end-diastolic volume index was < 140 mL/m2. Treatment was given tohigh preload, defined as a PAOP of > 18 mm Hg to prevent pulmonary edema. When PAOP and right ventricular end-diastolic volume index gave conflicting information, other clinical parameters were assessed to determine treatment. MEASUREMENTS AND MAIN RESULTS: Twenty-seven patients requiring 70 catheters were evaluated for the study. Thirteen patients with 46 pairs of data points completed the study. Fourteen patients were excluded from analysis due to irregular heart rate, poor quality of cardiac output at the time of volume infusion, or lack of major volume manipulation. PAOP and right ventricular end-diastolic volume index measurements agreed in 42 of 46 instances (PAOP of < 18 mm Hg, right ventricular end-diastolic volume index of < 140 mL/m2), leading to fluid treatment. In one instance, PAOP was > 18 mm Hg, right ventricular end-diastolic volume index was < 140 mL/m2, and the patient had normal blood pressure and good urine output. PAOP was used in this instance as a guide to diurese the patient, which led to improvement of heart rate and stroke volume index. Three measurements in two patients with high intra-abdominal pressure indicated a PAOP of > 18 mm Hg with right ventricular end-diastolic volume index of < 140 mL/m2. A rigid abdomen accompanied hypotension, tachycardia and low urine output. Thus, a fluid bolus was administered, resulting in improved blood pressure, stroke volume, and heart rate. PAOP were obtained at end-expiration. Positive end-expiratory pressure (PEEP) was removed for < 1 sec, if patients were on PEEP > or = 10 cm H2O, to avoid the effects of high intrapleural pressure on PAOP readings. Cardiac output was measured at end-expiration, and stroke volume index and right ventricular end diastolic volume index were derived. CONCLUSIONS: In this small sample of surgical patients with sepsis, adult respiratory distress syndrome, and hemorrhagic shock (n = 13), the additional information derived from right ventricular end-diastolic volume index did not change treatment in 43 of 46 instances. However, patients with increased intra-abdominal pressures may show misleadingly high PAOP despite low preload. These patients clearly benefitted from the additional information derived from ventricular volume measurements. Additionally, clinicians who are reluctant to take off-PEEP PAOP may also find this catheter useful.

Blood Pressure↗
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

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↗
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↗
PubMed1991

The home care practice and attitudes of Minnesota family physicians.

OBJECTIVE: Assess home care practice and attitudes of Minnesota family physicians (FPs). DESIGN: Mailed survey. SETTING: State of Minnesota. PARTICIPANTS: Members of the Minnesota Academy of Family Physicians, 80% of the FPs practicing in the state. INTERVENTION: A 55-item mailed, self-complete questionnaire regarding general practice and personal physician characteristics (18 questions), specific questions regarding geriatric and home care practice and related attitudes (37 questions); up to four reminder or follow-up surveys were sent. MAIN OUTCOME MEASURES: Descriptive summary of FP home care practice and attitudes. RESULTS: Eighty percent of surveys were completed, 76% of responding physicians made at least one home visit in the previous year, and 92% of home visits were to geriatric patients. Discriminant function analysis identified six significant (P less than 0.001) variables that explained 52% of the variance (r2 = 0.52, Wilks Lambda = 0.48) in home visiting behavior between frequent home visiting FPs (greater than 24 visits/year) and non-visiting FPs. FPs most likely to do home visiting were older and tended to have small group or solo practices in rural settings. CONCLUSION: The survey documented continued decline (from previously published surveys) of physician home visiting behavior and widespread dissatisfaction with reimbursement. However, attitudes regarding home care provided by other professionals were highly positive.

Attitude of Health Personnel↗