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Biomedical subjects

L Frey

Publications and source records attributed to L Frey.

At least 55 records · Page 3Linked to original sources

Efficacy and tolerability of diclofenac dispersible in painful osteoarthrosis.

A multicentre, twelve-week, double-blind, randomized trial was conducted to evaluate the efficacy and tolerability of diclofenac dispersible in patients suffering from osteoarthrosis of the knee and/or hip. Symptomatic adult patients (N = 129) of either sex were treated with diclofenac dispersible or the conventional enteric-coated tablet of diclofenac sodium 50 mg orally, thrice daily. Both formulations of diclofenac led to comparable and clinically significant reductions in the intensities of pain at rest and during activity within 1 week of therapy initiation. More than 70% of patients in both treatment groups had no or mild pain on full passive movement by the end of the study with the Lequesne Index showing a reduction of around 50% from initial values. Overall assessments of efficacy by the patient and the investigator indicated a positive response rate for both diclofenac formulations ranging between 71% and 82%. The proportion of patients reporting adverse effects, predominantly gastro-intestinal, was slightly higher in the dispersible group, 40.3%, compared to 37.3% with enteric-coated diclofenac sodium.

Diclofenac↗

[Monitoring by measurement of gastrointestinal mucosal pH value (pHi)].

Noninvasive measurement of mucosal pH by tonometry provides information on the adequacy of gastrointestinal mucosal oxygenation. The technique requires tonometer catheters (commercially available from Tonometrics) and a standard blood gas analyzer. After positioning of the catheter in the stomach or gut for at least 30 min, fluid is withdrawn from the prefilled balloon mounted on the catheter tip for pHi measurements. The pCO2 in the withdrawn fluid and bicarbonate concentration in the arterial blood are determined and pHi is calculated according to the Henderson-Hasselbalch equation. The tonometer technique has been validated in experimental studies and pHi has been shown to be a useful parameter to estimate adequacy of oxygenation of the mucosa surrounding the tonometer balloon. In surgical patients, pHi was found to be of high predictive value concerning incidence of complications; return of pHi towards higher values was found to be associated with a higher survival rate. In intensive care units, pHi-guided resuscitation proved to be superior to conventional therapy. Tonometric measurement of pHi is a useful parameter to monitor mucosal oxygenation and to provide information on the probability of complications and patient outcome. Further studies are needed in well-stratified patient groups with a present lower limit of pHi, triggering defined therapeutic interventions to improve mucosal oxygenation.

Acid-Base Equilibrium↗

[Blood replacement in elective surgery: results of the Sanguis Study].

The aim of the Sanguis study, a project sponsored by the European Community, is to assess the use of blood and blood components including the use of programs for autologous blood transfusion in 43 hospitals in 10 European countries. The study was inaugurated by Prof. G. Sirchia, Milan, who formed a study group of experts from 10 countries. The study group defined the study design, identified the centers, and followed the progress of the project. From October 1990 until September 1991 data were collected in the 43 hospitals from patients undergoing one of six elective surgical procedures. The results obtained from interim analysis (70% of expected data) of patients with total hip replacement revealed differences in the frequency of homologous blood transfusion between hospitals and also regional differences between different countries. There was great variation in the use of alternative programs for reduction or even avoidance of homologous blood transfusion between hospitals. For total hip replacement, the calculated probability to receive homologous blood varied between 0 and 100% in different hospitals. This observational study will provide a data base concerning the transfusion practice in 6 elective surgical procedures in 10 European countries. According to the findings of this study, recommendations for improving the transfusion practice shall be elaborated and indications for alternative programs identified. In a subsequent study (Sanguis 2), these recommendations are to be validated.

Aged↗

Wake up to managing customer relationships.

A survey of 50,000 American households on their habits in purchasing healthcare services shows that healthcare marketers need to "wake up" to managing their customer base more effectively before they miss critical opportunities to capture and retain business.

Attitude to Health↗

Hypertonic saline dextran resuscitation during the initial phase of acute endotoxemia: effect on regional blood flow.

BACKGROUND AND METHODS: Small-volume resuscitation by means of bolus application of hypertonic saline solutions has been demonstrated to restore central hemodynamics and regional blood flow in severe hemorrhagic and traumatic shock. The aim of this study was to elucidate the potential of this new concept for treatment of profound hypovolemia and microcirculatory deterioration associated with sepsis and endotoxic shock. In a porcine model of acute hyperdynamic endotoxemia (elicited by continuous iv infusion of Salmonella abortus equi endotoxin for 3.5 hrs), small-volume resuscitation applying hypertonic-hyperoncotic solutions was analyzed for its effect on central hemodynamics, oxygen delivery (Do2), and regional blood flow. Fluid therapy was initiated when the pulmonary artery occlusion pressure (PAOP) tended to decrease (at 43 to 52 mins of endotoxemia), and consisted of 4 mL/kg bolus infusion of either 7.2% sodium chloride, 10% dextran, or 10% dextran in 7.2% sodium chloride; thereafter, PAOP was maintained by controlled infusion of 6% dextran-60. In a control group, 6% dextran-60 was given without preinjection of hypertonic-hyperoncotic solutions. RESULTS: On small-volume resuscitation, cardiac index significantly increased within 5 mins in all groups, while mean arterial pressure remained unchanged. Fluid requirements were significantly reduced after small-volume resuscitation and the hyperdynamic circulatory state was maintained until the end of the observation period; Do2 as well as blood flow to heart, kidneys, and splanchnic organs remained high. CONCLUSION: Small-volume resuscitation by means of hypertonic saline-dextran proved the most effective, and seems to be an attractive supportive therapy to prevent microcirculatory failure in sepsis and endotoxemia.

Acute Disease↗

Optimizing autologous blood donation by recombinant human erythropoietin (rhu-EPO) and interleukin 3 (IL-3).

The transfusion of autologous blood protects surgical patients from both the transfusion transmitted diseases (AIDS, posttransfusion hepatitis) and the immunosuppressive effects of homologous blood. Nevertheless, the use of autologous blood is still unsatisfactory, mainly because of the elaborated logistics, organization and technique required and the often insufficient amounts of autologous blood gained. Today, the major growth-factors of erythropoiesis are available as recombinant analogues. In the studies reviewed here, we investigated the effects of rhu-EPO and IL-3 on perioperative erythropoiesis in two canine models of acute isovolemic hemodilution. Different therapeutic concepts are compared with respect to preoperative changes in hematocrit, the volume of autologous blood gained and the duration of postdilutional anemia.

Animals↗

Cloning and structure of the pyrE gene of Lactobacillus plantarum CCM 1904.

The pyrE gene of Lactobacillus plantarum CCM 1904, coding for the orotate phosphoribosyl transferase involved in the pyrimidine biosynthetic pathway, was cloned in Escherichia coli and sequenced. The predicted polypeptide sequence extending over 212 amino acids (MW 22,690) was compared to those of E. coli and to those of lower eukaryotes (Saccharomyces cerevisiae, Podospora anserina, Sordaria macrospora, Dictyostelium discoideum). Important conserved stretches were revealed, implying that these proteins are closely related.

Amino Acid Sequence↗

Suppression of cellular immune activity following severe head injury.

Infection is a major cause of morbidity following multiple traumatic and head injury. Although immunosuppression has been demonstrated after multiple traumatic injury, the effects of head injury on immune function have not been thoroughly investigated. In a prospective study of 10 severely head-injured patients, in vitro and in vivo parameters of cellular immune activity were assessed. In vitro measurements of lymphocyte surface antigen expression following mitogen stimulation were made serially over a 3-week period in 10 patients with severe head injury. The control group consisted of 20 healthy subjects. Phenotyping of peripheral blood lymphocytes (PBLs) was performed following incubation with and without mitogens. Phenotypes were determined by flow cytometry using monoclonal antibodies (MABs) to T lymphocyte subsets and the alpha subunit of interleukin 2 (IL-2) receptors. In vivo cellular immune function was determined by measuring patient responses to delayed-type hypersensitivity (DTH) skin testing within 24 h of injury. When head-injured patients were compared to controls, PBLs incubated in the presence of phytohemagglutinin (PHA) demonstrated a decrease in cells marking as T cells (p = 0.005), helper-inducer T cells (p = 0.001), and in the number of IL-2 receptor-bearing cells (p = 0.001). The functional ability of these lymphocyte subpopulations to proliferate in the presence of PHA was significantly suppressed within 24 h of injury and normalized within 3 weeks of injury. DTH skin testing to Candida, mumps, trichophyton, and PPD antigens was performed within 24 h of injury and resulted in anergic responses in all 10 patients when measured at 24, 48, and 72 h following administration. The overall infection rate was 60%, with the majority of infections occurring within the first 4 days following injury. The results of this study indicate that severe head injury results in suppression of cellular immune function with a corresponding high rate of infection. The possible significance of the decrease in the percentage of helper-inducer T cells and in the number of cells bearing IL-2 receptors following mitogen stimulation is discussed.

Adolescent↗

Structural organization of pLP1, a cryptic plasmid from Lactobacillus plantarum CCM 1904.

To construct shuttle vectors based on an endogenous replicon, we isolated a small cryptic plasmid (pLP1) from Lactobacillus plantarum CCM 1904. The nucleotide sequence (2093 bp, 38.25 GC mol%) revealed one major open reading frame encoding for a 317 amino acid protein (Rep). Comparisons with proteins encoded by other Gram-positive bacteria plasmids strongly suggest that the protein encoded by pLP1 has a replicative role. The presence of a consensus sequence including a tyrosine residue known to be the replication protein binding site to the DNA (in phage phi X174) strengthens this hypothesis. The DNA sequence contains also a sequence similar to the pC194 origin nick sequence, which initiates the plasmid replication at the plus origin, characteristic of plasmids which replicate following a rolling circle mechanism via single-stranded DNA intermediates. A set of 13 direct repeats of 17 bp could be involved in the expression of the incompatibility or in the copy number control as in the other plasmids. A promoter sequence located at the rep 5' region has been identified and is functional in Bacillus subtilis.

Amino Acid Sequence↗

Characterization, cloning, curing, and distribution in lactic acid bacteria of pLP1, a plasmid from Lactobacillus plantarum CCM 1904 and its use in shuttle vector construction.

A small 2.1-kb plasmid called pLP1 was extracted from Lactobacillus plantarum CCM 1904 (ATCC 8014) and cloned into the Escherichia coli pUC19 plasmid. As determined by DNA-DNA Southern hybridization with a pLP1-radioactively labeled probe, other lactic acid bacteria such as L. curvatus, L. sake, Carnobacterium, and Leuconostoc mesenteroides harbor pLP1-related plasmids. Shuttle vectors based on the pLP1 replicon were constructed by inserting the erythromycin-resistance gene from pVA891 into the various pUC19-pLP1 constructions. pLP1-based shuttle vector transformation efficiencies (TE) by electroporation were compared to TE of a broad-host-range plasmid pGK12 in different lactobacilli strains. Expression of the pUC19-pLP1 plasmids in Escherichia coli maxicells showed that pLP1 encodes for a 37,000 MW protein which can act in trans allowing the replication of plasmids in which this protein is truncated. The pLP1-based shuttle vectors producing this protein replicate in lactobacilli and also in Bacillus subtilis. A pLP1-free strain was obtained by incompatibility with a pLP1-based shuttle vector introduced in L. plantarum CCM 1904 by electroporation. The absence of pLP1 has no incidence on the strain phenotype suggesting that pLP1 is not essential for the strain in our laboratory conditions.

Cloning, Molecular↗

Long-term observation following traumatic-hemorrhagic shock in the dog: a comparison of crystalloidal vs. colloidal fluids.

The effect of volume replacement with crystalloidal and colloidal solutions was analyzed in 40 anesthetized Foxhounds subjected to a standardized traumatic-hemorrhagic shock. Following trauma and hypotension (MAP 40 mmHg; 3.0 +/- 0.5 hr) the animals were randomized to treatment with autologous blood and hydroxyethyl starch 6% (HES 450/0.7), or human serum albumin 5% (ALB), dextran-60 6% (DX), Ringer's lactate (RL), and hyperosmolar saline 1.3% (HS), respectively. While analgesia and sedation were maintained, the hemodynamic measurements were continued for a 24-hr period. Crystalloids and colloids were found equally effective in maintaining the macrohemodynamics following resuscitation from traumatic-hemorrhagic shock. To keep central hemodynamics at pre-shock level required at least four times higher volumes of crystalloids than colloids. No specific advantage for one of the substitutes tested was found with regard to accumulation of water in the lung during the first 24 hr following shock in dogs. Extravascular lung water (thermo-dye) and organ water (gravimetry) were not different between the groups. However, fluid loss into the abdominal cavity as well as albumin extravasation into lung interstitium and abdominal cavity were more pronounced in the crystalloid-treated animals, whereas albumin redelivery by the lymph was decreased. The deterioration of tissue oxygen extractions as well as the changes in acid-base balance in both crystalloid-treated groups reflect the persistent microcirculatory inhomogeneity in spite of normal macrohemodynamics.

Acid-Base Equilibrium↗

Fluid resuscitation in canine traumatic-hemorrhagic shock: long-term comparison of hydroxyethyl starch vs. Ringer's lactate.

In 16 anesthetized foxhounds a traumatic-hemorrhagic shock was performed. Following shock the dogs were randomized to treatment with autologous blood and either hydroxyethyl starch (HES, 450/0.5) or Ringer's lactate (RL). The animals were monitored for 24 h after treatment. The maintenance of normal cardiac output and left atrial pressure at pre-shock levels required 4.8 times more RL than HES. Extravascular lung water (EVLW) increased (p less than 0.01) with both treatment modalities without amelioration during the 24-hour observation period. No difference in EVLW was observed despite the higher infusion rate in the RL-group. Fluid loss into abdominal cavity, however was significantly lower (p less than 0.01) in the HES-treated animals. Albumin extravasation, on the other hand, was more pronounced (p less than 0.01) in the RL-group and, moreover, albumin redelivery by lymph was decreased (p less than 0.05). On the basis of this study, both fluid modalities appear to be equally effective in resuscitation from traumatic-hemorrhagic shock without interfering with pulmonary function and ARDS. The importance that the tissue albumin accumulation ranks for final outcome from shock, however, requires further investigation.

Animals↗

In vivo allergen tachyphylaxis in guinea pig lung is mediated by endogenous prostaglandin E biosynthesis.

The term "allergen tachyphylaxis" (AT) describes a progressively decreased bronchial reactivity to allergen exposition after repeated allergen challenge [in our test system measured by sequential inhalative antigen challenge of sensitized guinea pigs (GP)]. The hypothesis that AT is mediated by endogenous prostaglandin E (PGE) biosynthesis was tested in vivo on GP sensitized to ovalbumin (OA). Different groups of animals were challenged with simultaneous inhalation of OA (repeatedly at time 0, 10, 20, 60 and 70 min) together with inhibitors of PGE-biosynthesis ( parachloromercurobenzoic acid = PCMB, copper sulfate = Cu, copper dithiotreitol complex = CuDTT , dithiotreitol = DTT and dimercaptopropanol = DMP) or agents increasing PGE production (aurothioglucose = Au, zinc dithiotreitol complex = ZnDTT and reduced glutathion = GSH). Bronchial obstruction was measured by whole body plethysmography . PCMB, Cu, CuDTT , DTT and DMP inhibited AT, whereas Au and ZnDTT enhanced AT. Acetylsalicylic acid (ASA) treatment prevented AT. Aerosols of PGE2, but not of prostacyclin or prostaglandin D2 restored AT in ASA treated animals. In addition to these in vivo experiments in vitro investigations showed that PCMB, Cu and DTT decreased while ZnDTT increased PGE biosynthesis of allergen challenged GP lungs. It is concluded that AT, an important self-protecting mechanism of GP bronchial asthma, is mediated at least in part via endogenous PGE.

Allergens↗

Allergen tachyphylaxis of guinea pigs in vivo; a prostaglandin E mediated phenomenon?

Ovalbumin (OA) sensitized guinea pigs were repeatedly challenged with 1% OA in saline nebulized ultrasonically at the 0, 10, 20, 60 and 70th min. The intensity of bronchial obstruction was measured by body plethysmography. The first three challenges (0. 10, 20 min) caused strong asthmatic reactions in all animals, the last two (60, 70 min) only mild one in 10 out of 15 animals. The development of this "tachyphylaxis" was markedly reduced by pretreatment of the animals with cyclooxygenase inhibitors (indomethacin 10 mg/kg intraperitoneally resp, acetylsalicylic acid 10 mg/kg orally 2 h before tests). The effect of both inhibitors (i.e. inhibition of tachyphylaxis) was abolished by supplementing prostaglandin E2 as aerosol simultaneously to the allergen (100-200 ng per inhalation). The results suggest that allergen tachyphylaxis we have observed in vivo might be due to synthesis of cyclooxygenase products, e.g. prostaglandin E.

Aerosols↗