To be and to have a critical friend in medical teaching.

Background: In order to stimulate reflection and continuous professional development, a model of critical friends evaluating each other was introduced in medical education.

Objective: To investigate whether the critical friend concept can serve as a pragmatic model for evaluation of medical teachers and as a fruitful tool for enhancing self-knowledge and professional development among medical educators.

Methods: Three pairs of critical friends were formed, consisting of experienced medical teachers (n = 6) at the Karolinska Institutet.

[Chronic granulomatous disease--not only the lack of oxygen radicals].

Chronic granulomatous disease (CGD) is caused by mutations in the phox-family of superoxide ion generating enzymes. The clinical manifestations of CGD include increased infection susceptibility, a lupus like dermatitis and inflammatory bowel disease. The severe consequences of this rare disorder need to be handled by specialists, experienced in the care of CGD patients.

Adenosine treatment attenuates cytokine interleukin-6 responses to endotoxin challenge in healthy volunteers.

Anti-inflammatory effects of adenosine were evaluated in two randomized, double-blind, placebo-controlled studies. In one study healthy male volunteers received no endotoxin (adenosine study, n = 10), in the other intravenous endotoxin (4 ng/kg, endotoxin study n = 11) was given. All subjects were treated with adenosine infusion (40 microg/kg/min) and placebo (saline) infusion in a crossover design.

Nitric oxide and endothelin concentrations during intravenous infusion of urological irrigating fluid.

Objective: To study the possible role of two vasoactive mediators, nitric oxide (NO) and endothelin, in the hemodynamic alterations following absorption of irrigating fluid.

Material And Methods: Twelve male volunteers received an intravenous administration of 1.5% glycine, given at a rate of 0.

Modulation of plasma levels of soluble adhesion molecules and nitric oxide in healthy volunteers by exposure to swine dust.

Short-time exposure to swine dust causes an intense airways inflammation and symptoms of systemic inflammation in healthy volunteers. Here, we sought to study whether this response involved signs of endothelial cell activation. Peripheral blood cell counts and plasma levels of sE-selectin, sP-selectin, sICAM-1, interleukin-8, nitrite and nitrate were measured in blood samples from 17 healthy subjects before and after a 3-hr exposure to swine dust in a swine confinement building.

Airway reactivity and exhaled NO following swine dust exposure in healthy volunteers.

Short-time exposure to swine dust causes an intense inflammation of upper and lower airways and induces increased bronchial responsiveness to methacholine in previously non-exposed healthy volunteers. The objective to this study was to investigate the nasal inflammatory response and mucosal reactivity to swine dust exposure and whether nitric oxide metabolism is involved in the inflammatory process. Nitric oxide in expired air, nasal histamine test (NH), nasal lavage (NAL) and bronchial histamine challenges were studied before and after a 3 h exposure to swine dust in a swine confinement building in 17 non-smoking healthy subjects not previously exposed to farm dust.

Expression of nitric oxide synthases in subcutaneous adipose tissue of nonobese and obese humans.

Studies have shown evidence of production of nitric oxide (NO) in adipose tissue, as well as inhibition of lipolysis by NO. We have analyzed nitric oxide synthase (NOS) expression in subcutaneous adipose tissue from 13 nonobese and 18 obese male subjects. Using a competitive reverse transcription polymerase chain reaction method, endothelial (eNOS) and inducible (iNOS), but not neuronal (nNOS), nitric oxide synthase mRNA expression was detected in isolated fat cells and pieces of adipose tissue.

No effect of carvedilol on nitric oxide generation in phagocytes but modulation of production of superoxide ions.

Since carvedilol has been claimed to possess antioxidative effects, this drug might affect functional responses, including nitric oxide (NO) generation, of polymorphonuclear neutrophils (PMN) and macrophages. When we assessed the effects of carvedilol on PMN responses in vitro, we observed that carvedilol dose dependently modulated generation of superoxide ions by NADPH oxidase when induced by the formylpeptide formyl-methionyl-leucyl-phenylalanine (fMLP) or the phorbol ester phorbol myristate acetate. This effect was not coupled to diminished phospholipase C activity.

Electrochemical detection of nitric oxide production in human polymorphonuclear neutrophil leukocytes.

The detection of nitric oxide (NO) release by human polymorphonuclear neutrophil leukocytes (PMNs) presents several difficulties, mainly due to concomitant production of O2- and H2O2, which could interfere with the measurements. A Nafion and nickel porphyrin-coated microelectrode was used to measure NO production in PMNs in vitro. It allowed detection of 6.

Impaired granulocyte formylpeptide-induced superoxide generation in chronically ill, malnourished, elderly patients.

Objective: Protein-energy malnutrition (PEM), often occurring in patients with chronic disease, is associated with a decreased capacity to combat infections. In this study we assessed polymorphonuclear neutrophil (PMN) superoxide anion (*O2-) formation in elderly PEM patients with various chronic diseases.

Design And Subjects: Nineteen patients (75+/-1 years), with body mass index 17.

Gamma interferon treatment of patients with chronic granulomatous disease is associated with augmented production of nitric oxide by polymorphonuclear neutrophils.

Treatment with gamma-interferon (IFN-gamma) is associated with reduced frequency and severity of infections in chronic granulomatous disease (CGD), but the mechanism is unknown. Since the inducible nitric oxide (NO) synthase can be amplified by IFN-gamma in murine macrophages, for example, we hypothesized that IFN-gamma might modulate NO release from polymorphonuclear neutrophils (PMNs) in patients with CGD. Eight patients with CGD and eight healthy controls were studied.

Activation of nitric oxide release and oxidative metabolism by leukotrienes B4, C4, and D4 in human polymorphonuclear leukocytes.

Because arachidonate metabolites are potent mediators of inflammation, we have studied the effects of leukotriene B4 (LTB4) and the cysteinyl leukotrienes C4 and D4 (LTC4 and LTD4) on the release of nitric oxide (NO), in vitro, by human polymorphonuclear granulocytes (PMN). Two independent and highly sensitive real-time methods were used for these studies, ie, the NO-dependent oxidation of oxyhemoglobin (HbO2) to methemoglobin and a NO-sensitive microelectrode. When activated with LTB4, LTC4, or LTD4, but not with other lipoxygenase products such as 5S-HETE, 5-oxo-ETE or 5S, 12S-diHETE, PMN produced NO in a stimulus- and concentration-dependent manner.

Stimulus-dependent transduction mechanisms for nitric oxide release in human polymorphonuclear neutrophil leukocytes.

The production of nitric oxide (NO) may play an important role in functional responses of the human polymorphonuclear neutrophil granulocytes (PMNs). Others have described the presence of both an inducible, Ca2+-independent and a constitutionally expressed, Ca2+-dependent nitric oxide synthase (NOS) in human PMNs. However, the conditions for production and release of NO in human PMNs are still largely unknown.

Measurement of methemoglobin formation from oxyhemoglobin. A real-time, continuous assay of nitric oxide release by human polymorphonuclear leukocytes.

We have evaluated the spectrophotometric measurement (at 401 vs. 411 nm) of nitric oxide (NO)-dependent methemoglobin formation from oxyhemoglobin in order to assess NO release from human polymorphonuclear neutrophil leukocytes (PMN). S-nitroso-D,L-acetyl-penicillamine (SNAP, 25-200 microM), a donor of NO, induced a dose-dependent methemoglobin formation.

The role of nitric oxide in lipoxin A4-induced polymorphonuclear neutrophil-dependent cytotoxicity to human vascular endothelium in vitro.

Objective: To assess the mechanism for the cytotoxicity of human polymorphonuclear neutrophils (PMN) to human umbilical vein endothelial cells (HUVEC) induced by the 5- and 15-lipoxygenase product of arachidonate, lipoxin A4 (LXA4), and the phorbol ester, phorbol myristate acetate (PMA).

Methods: HUVEC were grown to confluence and labeled with 51Cr. PMN and stimuli were added, and the release of 51Cr into supernatants was assessed after 4 hours.

Neutrophil membrane potential changes and homotypic aggregation kinetics are pH-dependent: studies of chronic granulomatous disease.

Activated polymorphonuclear neutrophil granulocytes (PMN) from patients with chronic granulomatous disease (CGD) show reduced electron-proton shifts and an inability to acidify the cell. We studied whether this impaired pH-regulating capacity affected PMN membrane potential changes and the kinetics of homotypic aggregation by changing the extracellular pH over a wide range. At pH 7.

Natural interferon-alpha in combination with melphalan/prednisone versus melphalan/prednisone in the treatment of multiple myeloma stages II and III: a randomized study from the Myeloma Group of Central Sweden.

Three hundred thirty-five previously untreated patients with multiple myeloma in clinical stages II and III entered a randomized trial comparing intermittent oral melphalan and prednisone (MP) therapy (n = 171) with MP in combination with natural (leukocyte-derived) alpha-interferon (MP/IFN) (n = 164). The treatment groups were comparable with regard to major prognostic factors. The response frequency was 42% in the MP group and 68% in the MP/IFN group (P < .

Treatment of multiple myeloma with interferon alpha: the Scandinavian experience.

IFN alpha is a biologic therapeutic agent with documented antitumoral effect in multiple myeloma. 15% of previously untreated myeloma patients achieve a clinical response to IFN alpha alone with a possible dose-response relationship. A particularly good effect is noted in IgA myelomas treated with natural IFN alpha.

Effects of an essential fatty acid-supplemented diet on leukotriene B4-induced rat neutrophil functions.

This study evaluated the effect of dietary supplementation with the essential fatty acid linoleic acid to 10% of the energy content of a diet on the stimulus-response coupling of rat peritoneal neutrophils. When stimulated with leukotriene B4 neutrophils from essential fatty acid supplemented rats responded with a significantly more pronounced oxidative metabolism (assessed as luminol augmented chemiluminescence) relative to control cells from rats on a normal 3% of total energy essential fatty acid diet. Chemiluminescence response to the formylpeptide N-formyl-norleucyl-leucyl-phenylalanine-norleucyl-thyrosyl-leucine was similarly enhanced.

The effect of 20-trifluoromethyl leukotriene B4 on neutrophil functional responses.

20-trifluoromethyl-leukotriene B4 (20CF3-LTB4) is a stable derivative of leukotriene B4 (LTB4) that is not subjected to omega-oxidation to less active metabolites. 20CF3-LTB4 was as potent as LTB4 as a chemotactic, adhesion-promoting and aggregatory agent for human neutrophils, but had only 11 +/- 3% of the ability to induce an oxidative response. Nonetheless, both compounds were equally efficient in order to confer a rapid and monophasic increment of the concentration of cytosolic calcium.

Dietary linoleate supplementation modulates formyl-peptide receptor expression and functional responses of rat neutrophils.

We studied effects of dietary supplementation with the essential fatty acid (EFA) linoleic acid (LA) to see if neutrophil responses would be modulated. Neutrophils from rats maintained on a diet supplemented with EFA to 10% of the energy content--the high EFA (HEFA) group--showed a significantly higher LA concentration (but similar arachidonic acid content) compared with neutrophils from control rats maintained on a standard diet with 3% of the energy content as EFA. The HEFA group showed a significantly higher neutrophil oxidative metabolism compared with controls in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP), but this response was equal to control values when stimulated by ionophore A23187, sodium fluoride, or phorbol myristate acetate.

Oral versus intravenous melphalan and prednisone treatment in multiple myeloma stage II. A randomized study from the Myeloma Group of Central Sweden.

Eighty-one previously untreated patients with multiple myeloma stage II entered a randomized trial comparing oral melphalan (0.25 mg/kg/day; n = 40) with intravenous melphalan (0.125 mg/kg/day; n = 41) in combination with oral prednisone (2 mg/kg/day).

Substance P activates and modulates neutrophil oxidative metabolism and aggregation.

The substance P (SP) fragment SP(7-11) induced chemiluminescence (CL) and aggregation in human neutrophils at high concentrations (greater than or equal to 10 microM), whereas the entire molecule SP(1-11) was less potent and the SP(1-4) fragment was inactive. At these concentrations SP and its fragments also inhibited CL and aggregation evoked by subsequent addition of formyl-methionyl-leucyl-phenylalanine (fMLP), an effect that may depend on desensitization. However, at lower concentrations (1-10 nM) SP was able to prime human neutrophils to enhanced CL and enzyme release stimulated by fMLP.

Alternating combination chemotherapy (VMCP/VBAP) is not superior to melphalan/prednisone in the treatment of multiple myeloma patients stage III--a randomized study from MGCS.

86 previously untreated patients with multiple myeloma stage III entered a randomized trial comparing combination chemotherapy (VMCP/VBAP) (n = 42) with intermittent oral melphalan and prednisone (MP) treatment (n = 44). The treatment gropus were well comparable with regard to major prognostic factors. There was no statistically significant difference in the response rates, 52% (VMCP/VBAP) vs 61% (MP); in the response duration times, median 19 months vs 22 months, or in the survival times, median 24 months vs 28 months.