Clinical impact of chronic substance abuse in a Norwegian ICU-population.

BACKGROUND: The clinical impact of chronic substance abuse of alcohol and drugs-referred to as substance use disorders (SUD)-is often overlooked in the intensive care (ICU) setting. The aims of the present study were to identify patients with SUD-regardless of cause of admission-in a mixed Norwegian ICU-population, and to compare patients with and without SUD with regard to clinical characteristics and mortality. METHODS: Cross-sectional prospective study of a mixed medical and surgical ICU-population aged ≥18 years in Oslo, Norway. Data were collected consecutively, using a questionnaire including the AUDIT-C test, medical records and toxicology results. Patients classified with SUD were divided into the subgroups alcohol use disorders (AUD) and drug use disorders (DUD). RESULTS: Overall, 222 (26%) of the 861 patients included were classified with SUD; 137 (16%) with AUD and 85 (10%) with DUD. 130/222 (59%) of the SUD-patients had substance abuse-related cause of ICU-admission. Compared to non-SUD patients, DUD-patients were younger (median age 42 vs 65 years) and had lower SAPS II scores (41 vs 46), while AUD-patients had higher SOFA scores (8.0 vs 7.3). Overall, age-adjusted logistic regression analysis showed similar hospital mortality for SUD-patients and non-SUD patients, but AUD was associated with increased mortality among medical patients and in patients with sepsis (OR 1.7 (95% CI 1.0-2.8), and OR 2.6 (95% CI 1.1-6.2)). CONCLUSION: One in four ICU-patients had SUD regardless of cause of admission. Alcohol use disorder was associated with increased mortality in medical patients and in patients with sepsis.

Lower suicide intention in patients with personality disorders admitted for deliberate self-poisoning than in patients with other diagnoses.

BACKGROUND: People with deliberate self-poisoning and personality disorders are in increased risk for suicide. Intention and psychiatric features are important factors in a psychiatric evaluation and for planning aftercare. METHODS: Patients admitted to medical departments after deliberate self-poisoning were studied (n = 117). Patients with personality disorder according to (ICD-10, F.60-69) were compared to patients with affective disorders, substance use disorders, and unknown psychiatric diagnosis on Beck Suicide Intention Scale (SIS), Beck Suicide Ideation Scale (BSI), Beck Hopelessness Scale (BHS), and Beck Depression Inventory (BDI). RESULTS: The mean suicide intention score (SIS) was significantly lower among patients with personality disorders compared with patients with other psychiatric diagnoses 10.2 (95% CI 8.1-12.4) vs. 14.6 (95% CI 12.7-16.4) (p = 0.040). The hopelessness scores (BHS) were significantly higher among patients with personality disorders 13.0 (95% CI 10.9-15.2) compared with patients with affective disorders 8.2 (95% CI 6.1-10.3) and substance use disorders 9.9 (95% CI 5.2-14.6) (p = 0.0014) and unknown psychiatric diagnoses 10.6 (95% CI 9.1-12.2). There were no significant differences between the groups on suicide ideation (BSI) and depression (BDI). CONCLUSIONS: Although patients with personality disorders had lower suicide intention compared to patients with other psychiatric diagnoses, they reported significantly more hopelessness. This distinction is an important implication in the clinical assessment and planning of further treatment of DSP patients.

Impact of acute kidney injury on patient outcome in out-of-hospital cardiac arrest: a prospective observational study.

BACKGROUND: Kidney disease after out-of-hospital cardiac arrest (OHCA) is incompletely described. We examined the occurrence of acute kidney injury (AKI) in OHCA patients and impact of AKI, with or without renal replacement therapy (RRT), on 6-month mortality and neurological outcome. METHODS: Prospective study at Oslo University Hospital, Oslo, Norway. Adult resuscitated comatose OHCA patients treated with targeted temperature management at 33°C for 24 h were included. AKI and chronic kidney disease (CKD) were classified according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines. Main outcomes were 6-month mortality and good neurological outcome defined as Cerebral Performance Category 1-2. RESULTS: Among 245 included patients (84% males, mean age 61 years), 11 (4%) had previously known CKD and 112 (46%) developed AKI. Overall 6-month outcome revealed that 112 (46%) died and 123 (50%) had good neurological outcome. Compared with no kidney disease, the presence of AKI was significantly associated with 6-month mortality (odds ratio (OR) 3.17, 95% confidence interval (CI) 1.95-5.43, P < 0.001) and good neurological outcome (OR 0.28, 95% CI 0.16-0.48, P < 0.001). Six-month mortality (50 vs. 61%, P = 0.401) and frequency of good neurological outcome (44 vs. 35%, P = 0.417) were not statistically different in AKI patients with or without RRT, also after excluding patients where RRT was withheld due to futility. CONCLUSIONS: Kidney disease occurred in about half of patients successfully resuscitated from OHCA. Presence of AKI, but not RRT, was associated with unfavourable 6-month outcome.

Structured follow-up by general practitioners after deliberate self-poisoning: a randomised controlled trial.

BACKGROUND: General Practitioners (GPs) play an important role in the follow-up of patients after deliberate self-poisoning (DSP). The aim was to examine whether structured follow-up by GPs increased the content of, adherence to, and satisfaction with treatment after discharge from emergency departments. METHODS: This was a multicentre, randomised trial with blinded assignment. Five emergency departments and general practices in the catchment area participated. 202 patients discharged from emergency departments after DSP were assigned. The intervention was structured follow-up by the GP over a 6-month period with a minimum of five consultations, accompanied by written guidelines for the GPs with suggestions for motivating patients to follow treatment, assessing personal problems and suicidal ideation, and availability in the case of suicidal crisis. Outcome measures were data retrieved from the Register for the control and payment of reimbursements to health service providers (KUHR) and by questionnaires mailed to patients and GPs. After 3 and 6 months, the frequency and content of GP contact, and adherence to GP consultations and treatment in general were registered. Satisfaction with general treatment received and with the GP was measured by the EUROPEP scale. RESULTS: Patients in the intervention group received significantly more consultations than the control group (mean 6.7 vs. 4.5 (p = 0.004)). The intervention group was significantly more satisfied with the time their GP took to listen to their personal problems (93.1% vs. 59.4% (p = 0.002)) and with the fact that the GP included them in medical decisions (87.5% vs. 54. 8% (p = 0.009)). The intervention group was significantly more satisfied with the treatment in general than the control group (79% vs. 51% (p = 0.026)). CONCLUSIONS: Guidelines and structured, enhanced follow-up by the GP after the discharge of the DSP patient increased the number of consultations and satisfaction with aftercare in general practice. Consistently with previous research, there is still a need for interventional studies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01342809. Registered 18 April 2011.

Forest buffer-strips mitigate the negative impact of oil palm plantations on stream communities.

The global area cultivated with oil palm has doubled in the past two decades, causing deforestation, land-use change, freshwater pollution, and species loss in tropical ecosystems worldwide. Despite the palm-oil industry been linked to severe deterioration of freshwater ecosystems, most studies have focused on terrestrial environments, while freshwaters have been significantly less studied. We evaluated these impacts by contrasting freshwater macroinvertebrate communities and habitat conditions in 19 streams from primary forests (7), grazing lands (6), and oil palm plantations (6). In each stream, we measured environmental characteristics, e.g., habitat composition, canopy cover, substrate, water temperature, and water quality; and we identified and quantified the assemblage of macroinvertebrates. Streams in oil palm plantations lacking riparian forest strips showed warmer and more variable temperatures, higher turbidity, lower silica content, and poorer macroinvertebrate taxon richness than primary forests. Grazing lands showed higher conductivity and temperature, and lower dissolved oxygen and macroinvertebrate taxon richness than primary forests. In contrast, streams in oil palm plantations that conserved a riparian forest, showed a substrate composition, temperature, and canopy cover more similar to the ones in primary forests. These habitat improvements by riparian forests in the plantations increased macroinvertebrate taxon richness and maintained a community resembling more the one in primary forests. Therefore, the conversion of grazing lands (instead of primary forests) to oil palm plantations can increase freshwater taxon richness only if riparian native forests are safeguarded.

Testing the stress-gradient hypothesis with aquatic detritivorous invertebrates: insights for biodiversity-ecosystem functioning research.

1. The stress-gradient hypothesis (SGH) states that environmental stress modulates species interactions, causing a shift from negative interactions to net positive interactions with increasing stress. 2. Potentially, this modulation of species interactions could in turn influence biodiversity-ecosystem function (B-EF) relationships along stress gradients. Although the SGH has been extensively discussed in plant community ecology in the past two decades, it has received little attention from animal ecologists. 3. To explore whether the SGH could be applied to animal communities, we conducted a litter decomposition experiment with aquatic detritivorous invertebrates in which we manipulated litter quality and measured species interactions along this resource quality gradient. Litter quality was manipulated by presenting detritivores with leaves of plant species varying in specific leaf area and decomposition rate in streams. 4. We found a switch from negative to neutral interactions with increasing resource quality stress, in line with the SGH. However, by re-examining other published results with aquatic detritivores from the perspective of the SGH, we found that a diversity of patterns seem to characterize detritivore interactions along stress gradients. 5. Although the basic pattern proposed by the SGH may not apply to animal systems in general, we show that aquatic detritivore interactions do change along stress gradients, which underlines the importance of incorporating environmental stressors more explicitly in B-EF research.

Hair cortisol in polycystic ovary syndrome.

The aim of the study was to evaluate adrenal axis hyperactivation measuring hair cortisol levels, and its influence on the relationship among metabolic parameters, inflammation markers and androgens in adult women with PCOS. 44 women (18-34 years) with PCOS diagnosis and a control group of 49 healthy women (19-35 years) were included. In both gropus body mass index (BMI) was calculated and waist circumference (WC) was measured. Hair cortisol, total serum testosterone (TT), serum cortisol, 25 OH vitamin D (25OHD), insulin, high sensitivity C-reactive protein (hsCRP), triglycerides (TG), HDL cholesterol (HDL), glucose and leptin were measured. Bioavailable testosterone (bioT) was calculated. Hair cortisol concentration was higher and significantly different in PCOS patients compared to the control group (130 vs 63 pg/mg of hair, p < 0.001). Subsequently, patients with PCOS were divided into two groups according to hair cortisol levels: group 1 with normal hair cortisol concentration and group 2 with levels above the upper limit of the reference values (128 pg/mg of hair). In group 2, TT significantly correlated with 25OHD, hsCRP, TG/HDL index, BMI, WC, insulin and HOMA (p < 0.05); bioT correlated with hsCRP and leptin (p < 0.05). Finally, 25OHD was inversely correlated with leptin and with TG/HDL index (p < 0.05). High hair cortisol concentration in patients with PCOS confirmed hyperactivation of the HPA axis. The associations observed were only found in patients with PCOS with high hair cortisol levels (> 128 pg/mg of hair), showing a possible effect of HPA axis in these associations.

HIV viral load markers in clinical practice.

Plasma HIV RNA determinations are an important prognostic marker of disease progression and, when used appropriately, provide a valuable tool for the management of individual patients. But what constitutes appropriate use?

Acute poisonings treated in hospitals in Oslo: a one-year prospective study (I): pattern of poisoning.

OBJECTIVES: Prospective design is mandatory to study pattern of poisoning and suicidal intention of patients. MATERIAL AND METHODS: Prospective cross-sectional multi-center study of all patients contacting health care services because of acute poisoning during one year in Oslo, irrespective of intention. Data on the adult hospitalized patients (> or = 16 years) are presented here. RESULTS: Of a total of 3,775 such adult contacts (3,025 episodes), there were 947 (31 %) hospitalizations; annual incidence 1.9 (per 1,000) in males and 2.1 in females. Median age was 36 years (range 16-89); 54% females. Benzodiazepines (18%), ethanol (17%), paracetamol (12%), opioids (7%), and gamma hydroxybutyric acid (GHB) (7%) were most frequently taken. Patients stated suicidal intention in 29% of the admissions; physicians in 10%. CONCLUSION: Benzodiazepines and ethanol were the most common agents, but newer illicit drugs were frequent, especially GHB. Males often took ethanol and drugs of abuse; females often used prescription drugs with suicidal intention.

Expert opinion: fomepizole may ameliorate the need for hemodialysis in methanol poisoning.

Fomepizole is now the antidote of choice in methanol poisoning. The use of fomepizole may also change the indications for hemodialysis in these patients. We have addressed this change in a review of articles on methanol poisonings. Review of the literature (through PubMed) combined with our own experiences from two recent methanol outbreaks in Estonia and Norway. The efficiency of dialysis during fomepizole treatment was reported in only a few reports. One recent study challenged the old indications, suggesting a new approach with delayed or even no hemodialysis. Methanol-poisoned patients on fomepizole treatment may be separated into two categories: 1) The critically ill patient, with severe metabolic acidosis (base deficit >15 mM) and/or visual disturbances should be given buffer, fomepizole and immediate hemodialysis: dialysis removes the toxic anion formate, and assists in correcting the metabolic acidosis, thereby also reducing formate toxicity. The removal of methanol per se is not important in this setting because fomepizole prevents further production of formic acid. 2) The stable patient, with less metabolic acidosis and no visual disturbances, should be given buffer and fomepizole. This treatment allows for the possibility to delay, or even drop, dialysis in this setting, because patients will not develop more clinical features from methanol poisoning when fomepizole and bicarbonate is given in adequate doses. Indications and triage for hemodialysis in methanol poisonings should be modified. Delayed hemodialysis or even no hemodialysis may be an option in selected cases.

Clinical assessment compared to laboratory screening in acutely poisoned patients.

Acute poisonings may require identification of the toxic agents. It is impossible for routine laboratories to provide a full spectrum of toxicological analyses, and clinicians should know the reliability of the clinical diagnoses of toxic agents. We performed a 1-year study of hospitalized acute poisonings to determine the agreement between the clinical assessment on admission and serum laboratory tests for eight common toxic agents. Blood samples were drawn in 665 (70%) of the 947 admissions. The total number of laboratory found agents (967) exceeded the clinically suspected (871) by 11%. The agreement between the clinical assessment and laboratory analyses was good for ethanol and paracetamol (kappa = 0.70 for both), whereas only moderate or fair for other agents (kappa 0.22-0.51). Sensitivities of the clinical assessments compared to the laboratory results were better for common than rare agents, and better for higher than lower serum concentrations. The four most common agents (ethanol, benzodiazepines, paracetamol, and opiates) had overall sensitivity of 82% for higher-than-median serum concentrations, whereas the other agents had sensitivities ranging from 14% to 71% for higher-than-median concentrations. The reliability of the clinical diagnoses varied to such an extent that agents, which are important to recognize for specific treatment, should be tested for.

Postmenopausal HRT and tibolone in relation to muscle strength and body composition.

OBJECTIVES: Sarcopenia, the loss of muscle mass with age, has a great impact on physical function, and especially in postmenopausal women, who experience a greater decline in muscle strength than do men of similar age. Conventional hormone replacement therapy (HRT) may diminish this loss of muscle strength and may even increase muscle strength. However, HRT is not currently promoted for this indication because of its negative side effects, which is why tibolone, a synthetic steroid with oestrogenic, progestogenic, and androgenic activity, may be an alternative option. The aim of this article was to review data on the effect of HRT and tibolone on muscle strength and body composition in postmenopausal women. METHODS: Medline, Pubmed, Embase, and Sumsearch were searched for articles on the effect of HRT and tibolone on muscle strength and body composition, using the Mesh terms hormone replacement therapy and clinical trial combined with muscle strength or body composition. Tibolone was added as search term with clinical trial and muscle strength or body composition. RESULTS: Three of five randomized controlled trials reported a significant positive effect of HRT on muscle strength but not on body composition. Tibolone significantly increased handgrip strength and isometric knee extension strength in one randomized placebo-controlled, double-blind trial and increased mean knee extensor strength in one cross-sectional study. Tibolone also increased the lean body mass and decreased the accumulation of body fat. CONCLUSIONS: HRT and tibolone increase muscle strength. Unlike HRT, tibolone also increases lean body mass and significantly reduces the total body fat content. Further research is recommended to determine whether tibolone is a safe treatment for sarcopenia.

Methanol mass poisoning in Estonia: outbreak in 154 patients.

BACKGROUND: Knowledge of methanol toxicity is based on human data from case series and larger outbreaks. In many of these cases, however, diagnosis was not verified by methanol determinations. We present epidemiological and clinical data from one of the largest methanol outbreaks in which all patients had detectable serum methanol levels. METHODS: Retrospective case series study of hospital and forensic charts from the five hospitals where patients were treated. RESULTS: Of the 147 patients admitted with suspected methanol poisoning, the diagnosis was confirmed in 111, of whom 25 (23 %) died. In addition, 43 patients died outside the hospital, giving a total of 154 patients and a death toll of 68 (44 %). Outcome was related to the degree of metabolic acidosis, serum methanol concentration, coma upon admission, and the patient's ability to hyperventilate. Patients were treated with bicarbonate (85 %), ethanol (87 %), hemodialysis (71 %), and mechanical ventilation (61%) according to clinical features and blood gases, since serum methanol concentrations were analyzed retrospectively. Twenty patients (18 %) survived with permanent sequelae, 18 suffered from impaired vision, and 3 developed permanent brain damage. DISCUSSION: Given limited resources, triage and use age of tertiary care centers allowed a small community hospital to treat a high number of methanol-poisoned patients. Critical resources were ventilators and dialyzing machines, whereas stores of antidote (ethanol) and bicarbonate were sufficient. Many patients were mechanically ventilated by hand and treated with bicarbonate and ethanol during transport to tertiary care centers for hemodialysis.

Clinical vs. laboratory identification of drugs of abuse in patients admitted for acute poisoning.

OBJECTIVE: The extent of drug abuse in patients admitted for self-poisonings is uncertain. The aim of this study was to assess the pattern of drugs of abuse among patients admitted for acute poisoning according to age and gender, and to study the concordance between the clinical assessments by the physicians on duty and the drug analyses. METHODS: Prospective cross sectional study of all patients (n = 405, 52% males, median age 31 years) treated for acute poisoning in our department during one year (2001). The physician on-call classified type of drug of abuse by history and clinical assessment. This was later compared to urine and blood samples analysed for ethanol, benzodiazepines, opiates, cocaine, ecstasy, GHB, amphetamine and cannabis. RESULTS: In 320 admissions (79%), the comparison between clinical diagnosis and laboratory analyses could be performed. A total of 478 drugs were suspected and 621 were found. The main toxic agents found were benzodiazepines (49.7%), ethanol (40.3%), opiates (35.3%), cannabis (23.8%) and amphetamine (21.3%). Ninety-two had used drugs of abuse. The agreement between clinical assessments and laboratory findings was best for GHB and ethanol (kappa = 0.43), and for opiates (k = 0.38). For benzodiazepines and cannabis, the concordance was poor (k = 0.18 and 0.10, respectively). However, the correct clinical evaluation for these substances was 59% and 77%, respectively. CONCLUSIONS: Drugs of abuse were more frequently found than suspected clinically. Benzodiazepines, ethanol and opiates were most common. The agreement between clinical assessment and drug analyses was moderate to low. Physicians seem to underestimate the use of these drugs.

Proposed mechanism of therapeutic selectivity for 9-beta-D-arabinofuranosyl-2-fluoroadenine against murine leukemia based upon lower capacities for transport and phosphorylation in proliferative intestinal epithelium compared to tumor cells.

Studies have examined transport and phosphorylation of 9-beta-D-arabinofuranosyl-2-fluoroadenine (F-Ara-A), a deaminase resistant adenosine analogue, as mechanisms that could mediate the observed therapeutic efficacy of this agent against murine tumor models. Earlier finds by Avramis and Plunkett (Cancer Res., 42: 2587-2591, 1982) showed markedly less accumulation in vivo of administered F-Ara-A as cytotoxic triphosphate in gastrointestinal mucosa and bone marrow compared to P388 cells. We have pursued the basis for this difference in vitro using L1210 ascites and proliferative epithelial cells (85-95% crypt cells) isolated from mouse small intestine as representative sample populations of drug-sensitive tumor and drug-limiting normal regenerative host tissue. Using a rapid sampling technique, linear initial rates of substrate uptake were established at 25 degrees C for radiolabeled F-Ara-A and adenosine at a concentration range of 1-1000 microM. The relationship between velocity of initial transport and substrate concentration is indicative of Michaelis-Menten saturation kinetics for both substrates. Competition studies between F-Ara-A and adenosine suggest a common route of entry for both substrates in crypt epithelial cells. Results from double-reciprocal analysis of the velocity versus concentration data are consistent with a simple carrier-mediated facilitated diffusion process with Km, V25max, and Ki values of 317 +/- 44 (SE) microM, 49 +/- 7 nmol/s/g dry weight, and 301 +/- 34 microM for F-Ara-A, and 264 +/- 14 microM, 44 +/- 5 nmol/s/g dry weight, and 225 +/- 44 microM for adenosine, respectively. The presence of a single low-affinity carrier in the proliferative epithelial cells contrasts sharply with the high affinity (Km, 68 +/- 14 microM; V25max, 48 +/- 4 nmol/s/g dry weight) and low-affinity (Km, 326 +/- 48 microM; V25max, 124 +/- 44 nmol/s/g dry weight) routes of entry documented for L1210 cells. This differential in transport kinetics conveys a 7- to 8-fold greater capacity to L1210 ascites compared with crypt epithelial cells for uptake of the antitumor agent F-Ara-A. At pharmacologically achievable concentrations of F-Ara-A and in view of this differential, influx of F-Ara-A would be more rate limiting to phosphorylation of F-Ara-A in epithelial cells than in L1210 cells. Metabolism studies with L1210 ascites and proliferative intestinal epithelial cells show that intracellular phosphorylation of F-Ara-A is also elevated in L1210 cells.(ABSTRACT TRUNCATED AT 400 WORDS)

The dynamics of cobalamin utilization in L-1210 mouse leukemia cells: a model of cellular cobalamin metabolism.

The uptake and metabolism of cobalamin (Cbl) has been studied in L-1210 murine leukemia cells propagating in vitro. Extracellular Cbl (protein bound and free) and intracellular Cbl (protein bound and free) were determined after culturing L-1210 cells in the presence of [57Co]cyanocobalamin (CN-Cbl) bound to transcobalamin II (transcobalamin, TC). The intracellular pool of free [57Co]Cbl increased during the first 24 h of culture and a substantial fraction of this free pool was effluxed from the cell to the medium. Upon depletion of extracellular TC-[57Co]CN-Cbl, the intracellular concentration of free Cbl decreased as did the efflux of Cbl to the medium. Internalized [57Co]CN-Cbl was converted to hydroxocobalamin (OH-Cbl), methylcobalamin (Me-Cbl) and 5'-deoxyadenosylcobalamin. These Cbl forms were found in both soluble (cytoplasmic) and insoluble (membrane) fractions. Intracellular protein-bound [57Co]Cbl fractionated with methionine synthase (MS) and methylmalonyl-CoA mutase (MU) activity. The major form of Cbl associated with the two enzymes was OH-Cbl. Cells propagated in medium containing N5-methyltetrahydrofolate and homocysteine showed a substantial increase in MS activity which paralleled the increase in the intracellular concentration of Me-Cbl and the Cbl bound to the enzyme.

Homocysteine induces expression and secretion of monocyte chemoattractant protein-1 and interleukin-8 in human aortic endothelial cells: implications for vascular disease.

BACKGROUND: Proinflammatory cytokines play key roles in atherogenesis and disease progression. Because hyperhomocysteinemia is an independent risk factor for cardiovascular disease, we hypothesized that homocysteine could be atherogenic by altering the expression of specific cytokines in vascular endothelial cells. METHODS AND RESULTS: Northern blot and RNase protection assays showed that DL-homocysteine induced mRNA expression of the proinflammatory cytokines monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) in cultured human aortic endothelial cells (HAECs). Homocysteine had no effect on expression of other cytokines, namely tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor, interleukin-1beta, and transforming growth factor-beta. MCP-1 mRNA expression increased 1 hour after homocysteine treatment, reached a maximum within 2 to 4 hours, and declined to basal levels over the next 24 hours. Induction of mRNA expression for both chemokines was observed with as little as 10 micromol/L DL-homocysteine, and maximal expression was achieved with 50 micromol/L DL-homocysteine. Homocysteine also triggered the release of MCP-1 and IL-8 protein from HAECs into the culture medium. The induction was specific for homocysteine, because equimolar concentrations of L-homocystine, L-cysteine, and L-methionine had no effect on mRNA levels and protein release. Furthermore, L-homocysteine induced chemokine expression, but D-homocysteine did not, thus demonstrating enantiomeric specificity. The culture medium from homocysteine-treated HAECs promoted chemotaxis in human peripheral blood monocytes and U937 cells. Anti-human recombinant MCP-1 antibody blocked the migration. CONCLUSIONS: Pathophysiological levels of L-homocysteine alter endothelial cell function by upregulating MCP-1 and IL-8 expression and secretion. This suggests that L-homocysteine may contribute to the initiation and progression of vascular disease by promoting leukocyte recruitment.

Serum glutathione in adolescent males predicts parental coronary heart disease.

BACKGROUND: Traditional risk factors account for only half of the morbidity and mortality from coronary heart disease (CHD). There is substantial evidence that oxidative injury plays a major role in the atherosclerotic process. Thus, antioxidants may protect against development of atherosclerosis. Glutathione, an intracellular tripeptide with antioxidant properties, may be protective. METHODS AND RESULTS: This case-control study compared total serum glutathione (tGSH) in 81 adolescent male offspring of parents with premature CHD (ie, before 56 years of age) and 78 control male offspring of parents without known or suspected CHD. Case offspring had significantly lower tGSH than control offspring. In multiple logistic regression with parental CHD status as the dependent variable, age entered as a covariate, and other CHD risk factors competing to enter the model as significant independent predictor variables, LDL cholesterol (odds ratio [OR], 2.15 [units=1.5 SD]; 95% CI, 1.21 to 3.82), tGSH (OR, 0.40; 95% CI, 0.22 to 0.71), HDL cholesterol (OR, 0.42; 95% CI, 0.22 to 0.78), and total serum homocysteine (OR, 2.6; 95% CI, 1.35 to 5.02) entered the model as significant predictors of parental CHD status. CONCLUSIONS: Low tGSH in adolescent boys is a significant independent predictor of parental CHD, in addition to elevated LDL cholesterol, low HDL cholesterol, and elevated total serum homocysteine concentrations.

Homocysteine and coronary atherosclerosis.

Homocysteine is increasingly recognized as a risk factor for coronary artery disease. An understanding of its metabolism and of the importance of vitamins B6 and B12 and folate as well as enzyme levels in its regulation will aid the development of therapeutic strategies that, by lowering circulating concentrations, may also lower risk. Possible mechanisms by which elevated homocysteine levels lead to the development and progression of vascular disease include effects on platelets, clotting factors and endothelium. This review presents the clinical and basic scientific evidence supporting the risk and mechanisms of vascular disease associated with elevated homocysteine concentrations as well as the results of preliminary therapeutic trials.

Fomepizole may change indication for hemodialysis in methanol poisoning: prospective study in seven cases.

BACKGROUND: Treatment of methanol poisoning includes administration of buffer, antidote and hemodialysis. The role of hemodialysis using the new antidote fomepizole has not been studied. We studied the kinetics of methanol and formate during hemodialysis, and the possibility for delayed hemodialysis in the methanol poisoned patients without severe metabolic acidosis or visual disturbances. PATIENTS AND METHODS: Prospective case series study on methanol, formate and dialysis kinetics in 7 cases of severe methanol poisoning treated with buffer, fomepizole and hemodialysis (average 7 hours, range 5 - 8). Four patients were dialyzed early after diagnosis was obtained, while three were dialyzed "electively" the next day. RESULTS: The median pH upon admission was 6.9 (range 6.6 - 7.5) and median base deficit 20.4 mmol/l (range 5.1 - 30.0). Their median S-methanol was 76.3 mmol/l (range 15.6 - 140.6) and S-formate 13.6 mmol/l (range 3.3 - 21). The median half-life of methanol during fomepizole treatment before dialysis was 71.2 hours (range 69.3 - 77); compared to 2.5 hours (range 1.7 - 3.3) during procedure. The median half-life of formate during dialysis was 1.7 hours (range 1.5 - 1.9). The median dialysis clearance of methanol was 222 ml/min (range 204 - 232) and for formate 225 ml/min (range 220 - 229) at a blood flow of 250 ml/min. One patient died and 2 were discharged with permanent visual and cerebral sequelae, whereas one died one year later. All three patients, in whom "elective" hemodialysis was performed, were discharged without sequelae. CONCLUSION: The efficacy and side effect profile of fomepizole may change the role of hemodialysis in methanol poisoning. More patients may be stabilized in local hospitals and transferred for "elective" dialysis, if methanol removal is still indicated after correction of metabolic acidosis.