Treatment-resistant depressed patients show a good response to Mindfulness-based Cognitive Therapy.

Mindfulness-based Cognitive Therapy (MBCT) is a class-based programme designed for use in the prevention of relapse of major depression. Its aim is to teach participants to disengage from those cognitive processes that may render them vulnerable to future episodes. These same cognitive processes are also known to maintain depression once established, hence a clinical audit was conducted to explore the use of MBCT in patients who were currently actively depressed, and who had not responded fully to standard treatments. The study showed that it was acceptable to these patients and resulted in an improvement in depression scores (pre-post Effect Size=1.04), with a significant proportion of patients returning to normal or near-normal levels of mood.

Feasibility study of the spectroscopic measurement of oxyhemoglobin using whole blood without pre-treatment.

A feasibility study was carried out to evaluate a chemometrics-enhanced measurement of oxyhemoglobin concentration in whole blood without pre-treatment by lysing cellular components in the sample. Conventional in vitro multi-wavelength CO oximeters pre-process blood by sonication or detergent dilution to lyse blood cells to reduce light scattering. Two limitations result: (1) residual cell membrane fragments can seed surface biofouling and (2) dilution errors can occur. A full wavelength method using multivariate analysis in chemometrics was applied to correct the light scattering effect in the measurement of oxyhemoglobin concentration. Whole blood specimens were adjusted to different oxyhemoglobin concentrations with gas mixtures (N2, CO2 and O2). An Ocean Optics miniaturized spectrophotometer with a 100 microns pathlength optical cell was used for transmission measurements from 500 to 700 nm. Original spectra were smoothed and a second derivative transformation was performed to eliminate the baseline shift and slope changes from light scattering. Indirect calibration was applied to the second derivative spectra. Two-factor cross-validation by principle components regression on two sets of data showed r2 = 0.985 and 0.946 between predicted oxyhemoglobin concentration and those measured by an AVL 912 CO oximeter with RSD = 3.85 and 6.83%, respectively. Error analysis gave s = 2.36 x 10(-5) (RSD = 0.23%) on derivative absorbance for the spectrophotometer measurement alone. Specimen settling and specimen sampling gave imprecision on derivative absorbance of s = 6.17 x 10(-4) (RSD = 4.4%) and s = 4.52 x 10(-4) (RSD = 1.4%), respectively.

Circadian temperature and cortisol rhythms during a constant routine are phase-delayed in hypersomnic winter depression.

Circadian temperature, cortisol, and thyroid-stimulating hormone (TSH) rhythms during a constant routine were assessed in 6 female controls and 6 female patients with hypersomnic winter depression (seasonal affective disorder, SAD) before and after morning bright light treatment. After sleep was standardized for 6 days, the subjects were sleep-deprived and at bed rest for 27 hours while rectal temperature, cortisol, and TSH levels were assessed. The minimum of the fitted rectal temperature rhythm was phase-delayed in the SAD group compared to the controls 5:42 AM vs. 3:16 AM (p < .005); with bright light treatment, the minimum advanced from 5:42 AM to 3:36 AM (p = .06). The minimum of the cortisol rhythm was phase-delayed in the SAD group compared to the control group, 12:11 AM vs. 10:03 PM (P < .05); with bright light treatment, the minimum advanced from 12:11 AM to 10:38 PM (P = .06) [corrected]. The acrophase of the TSH rhythm was not significantly phase-delayed in SAD subjects compared to control, though the trend appeared to be toward a phase-delay (p = .07). After bright light therapy, the TSH acrophase was not significantly different in the SAD subjects; the trend was a phase-advance (p = .09). Overall, the data suggest that circadian rhythms are phase-delayed relative to sleep in SAD patients and that morning bright light phase-advances those rhythms.

A case of sulfhemoglobinemia and emergency measurement of sulfhemoglobin with an OSM3 CO-oximeter.

We describe a case of sulfhemoglobinemia associated with toxic paint ingestion. Blood gases, oxygen content, and fractional hemoglobin derivatives were assayed with Radiometer 520 and OSM3 instruments. Although the CO-oximeters indicated the presence of sulfhemoglobin (SulfHb), the results were not quantitative. An OSM3 service software program was activated to obtain the actual concentrations of the hemoglobin fractions. Subsequently, we evaluated the performance of the OSM3 service program for the analysis of SulfHb by performing precision studies and comparing OSM3 results with those of an AVL 912 CO-oximeter. Retrospectively, we determined that the patient's specimens contained 6% SulfHb. There was an obvious deviation between standard OSM3 oxyhemoglobin fraction measurements and those obtained by using its service program-the effect of a high SulfHb content.

Association of elevated umbilical cord blood creatine kinase and myoglobin levels with the presence of cocaine metabolites in maternal urine.

STUDY OBJECTIVE: To determine whether an association exists between antenatal cocaine exposure and elevated levels of creatine kinase (CK) and myoglobin in umbilical cord blood collected upon delivery. STUDY POPULATION: 105 anonymous maternal urines with corresponding infant umbilical cords bloods. METHODS: Maternal urines were screened for cocaine metabolites by the Syva EMIT assay, with positive specimens confirmed by gas chromatography/mass spectrometry. For all 8 positives, plus the first 47 of the negatives collected, matched infant cord blood specimens were analyzed for myoglobin by radioimmunoassay and CK by kinetic enzyme activity assay. Cord bloods matched to the remaining 50 cocaine-negative urines were not analyzed. A two-tailed Mann-Whitney test was used to evaluate the significance of differences in CK and myoglobin levels between the two groups. RESULTS: CK levels were evaluated twofold in the cocaine-positive group as compared to the cocaine negative group (mean 383 +/- 260 vs. 189 +/- 68 IU/L, p = 0.005). Myoglobin levels were twofold higher in the cocaine-positive group compared to the cocaine negative group (mean 55.9 +/- 37.1 vs. 33.3 +/- 26.8 ng/mL, p = 0.077). CONCLUSION: Antenatal cocaine exposure is associated with elevated cord blood CK, and possibly with elevated cord blood myoglobin. Additional studies, using larger study populations and more sensitive methods of detecting antenatal cocaine exposure, along with detailed follow-up examination of infants, are indicated.

Blood ionized magnesium concentrations during cardiopulmonary bypass and their correlation with other circulating cations.

BACKGROUND AND AIM: The recent introduction of new measurement technology (using ion specific electrodes) makes intraoperative evaluation of blood ionized magnesium (Mg2+, or iMg)--the bioactive fraction of circulation magnesium--possible. The goals of this study were: (1) to examine the longitudinal pattern(s) of change in blood iMg during cardiopulmonary bypass (CPB); and (2) to determine the relationship of iMg to Ca2+ (iCa), K, pH, Na, and hematocrit (Hct) during CPB. METHODS: Blood was collected serially before, during, and after CPB on 30 patients undergoing elective coronary artery bypass graft procedures and the iMg was measured with an AVL Scientific Corp., model 988-4 instrument. RESULTS: Overall, 73% of iMg results were abnormally low, 50% during CPB. Some cases had both hypo- and hyperionized magnesemic episodes. There were low iCa during CPB in 97% of cases. Using Spearman's rank order correlations and p < 0.05, iMg and K were directly correlated before, during, and after bypass, suggesting their parallel movement between tissue and blood. iMg and iCa were directly correlated before, and inversely correlated after, CPB, but unassociated during bypass. iMg and Na were inversely correlated after bypass in all cases. iMg was inversely correlated to pH and positively correlated to Hct during CPB only, and only in patients with concurrent association of iMg and iCa. CONCLUSIONS: Blood iMg depletion occurs frequently in CPB patients. iMg changes are not readily predictable. The association of intraoperative iMg depletion with postsurgical atrial fibrillation--reported to have a hypomagnesemic connection- should be investigated.

Circulating total and ionized magnesium after ethanol ingestion.

Hypomagnesemia is associated with alcoholism (Lim P, Jacob E. Metabolism 1972;21:1045-51). Here we assess two measurements of blood magnesium in emergency care patients with confirmed ethanol ingestion. Serum total and ionized magnesium (tMg, iMg) were measured in 88 patients with ethanol concentrations of 6-128 mmol/L and in sera of 97 hospitalized patients (control group). iMg was measured by an ion-selective electrode method; tMg was measured spectrophotometrically. iMg was significantly lower for the ethanol-containing specimens (0.35 +/- 0.12 mmol/L, mean +/- SD) than for the control group (0.46 +/- 0.15 mmol/L), with P <0.0001. The tMg for the test group (0.87 +/- 0.20 mmol/L) was not significantly different from the controls (0.88 +/- 0.33 mmol/L), with P = 0.5987. tMg was not well-correlated with iMg in the ethanol-positive specimens. Most ethanol-positive patients had abnormally low serum iMg (87 of 88 had iMg <0.53 mmol/L).

Effect of antibody specificity on results of selected digoxin immunoassays among various clinical groups.

We examined the specificity of three automated digoxin immunoassays (Abbott TDxFLx Digoxin II assay, Baxter-Dade Stratus II Digoxin assay, and Ciba Corning ACS Digoxin assay) applied without modification to (a) sera from 229 digoxin-free patients in 12 cohorts associated with nonspecific or endogenous digoxin-like immunoreactive factor (DLIF) interference, and (b) drug-free serum supplemented with the major metabolites and analogs of digoxin. We observed three patterns of apparent digoxin results among the DLIF samples: one common to kidney and liver failure patients, where TDx and Stratus assays showed significant positive results; one common to newborns and cord blood, where only the TDx assay had significant interference; and one from cardiac surgery patients, where the Stratus assay alone showed interference. Of the three assays, the ACS had the least interference from DLIF. The assays also behaved differently with respect to cross-reactivity with digoxin metabolites, digitoxin, and digitoxin metabolites. The ACS assay again had the least analog or metabolite cross-reactivity. The three methods agreed well on digoxin-positive specimens, with a mean bias of <0.15 microgram/L digoxin for each and discrepancies (defined as >3 SD between the assay pairs compared) of only 3-5%.

Application of a novel fiber-optic biosensor in situ to investigate the metabolic effect of lactate infusion.

Recently developed biosensor technology, which allows near real-time measurement in situ of gas tension (pCO2 and pO2) and of pH, was applied to arterial blood, cerebrospinal fluid (CSF), and brain parenchyma during intravenous lactate infusion in monkeys. Comparison of simultaneous biosensor measurements and discrete arterial blood sampling for traditional blood gas analyses indicated a high level of correlation for pCO2, pO2, and pH. Arterial pO2 and pH values were significantly higher and pCO2 significantly lower than corresponding CSF and brain parenchyma values at baseline, during and following lactate infusion. There was a divergence between arterial and brain parenchyma pH and pO2 measurements. Lactate infusion was associated with progressive arterial pH rises, consistent with the production of a metabolic alkalosis. Cerebrospinal fluid pCO2 remained unchanged during and following lactate infusion. Brain parenchyma exhibited a complex pattern of response characterized by a trend for pO2 and pH to decrease during lactate infusion, which reversed following completion of the infusion. These observations are suggestive of a transient hypoxia from decreased cerebral blood flow and/or reduced oxyhemoglobin dissociation during lactate infusion, but verification of these results is required.

Specific heparin preparations interfere with the simultaneous measurement of ionized magnesium and ionized calcium.

OBJECTIVE: To determine whether heparin anticoagulants used for analysis of whole blood ionized calcium would influence the measurement of ionized magnesium. METHODS: The effects of zinc heparin, lithium heparin, and electrolyte-balanced heparin on the simultaneous measurement of ionized magnesium and ionized calcium in serum were determined using ion selective electrodes. RESULTS: Time-dependent biases in ionized magnesium and calcium concentrations were apparent with zinc heparin but not with lithium or electrolyte-balanced heparin. Ionized magnesium and calcium concentrations were more significantly influenced by volume-dependent changes in zinc heparin potency than with lithium or electrolyte-balanced heparin. CONCLUSION: Zinc heparin produces a significant positive bias in the simultaneous determination of ionized magnesium and ionized calcium concentrations.

Zinc heparin introduces a preanalytical error in the measurement of ionized calcium concentration.

In this study we determined how zinc heparin affected ionized calcium concentration determinations. Zinc heparin produced a positive bias (0.020-0.067 mmol l-1) in ionized calcium measurement in serum/whole blood and a negative bias (-0.035 to -0.110 mmol l-1) with aqueous ionized calcium standards. To test if the positive bias was due to zinc ions displacing calcium from its protein-calcium complexes, we reproduced the effect by adding ZnCl2 to pooled serum. Changes in [ZnCl2] (0.1-0.5 mmol l-1) caused a dose-dependent increase, a constant bias ([ZnCl2], 0.5-1.25 mmol l-1) or a dose-dependent decrease ([ZnCl2] > 1.25 mmol l-1) in ionized calcium concentration, independent of pH. Similar results were obtained when zinc concentration of the specimen was changed by varying the volume of blood collected into syringes containing zinc heparin. We conclude that zinc heparin produces a positive bias in ionized calcium measurement in protein-based matrices.

Amplification of serotonin-induced arterial contractions with thrombin.

The purpose of this study was to determine if exposure of arteries to thrombin increases arterial sensitivity to serotonin and could thereby promote vasospasm. Rings of rabbit abdominal aorta, with endothelium intact or removed, were pretreated with vehicle or thrombin (2.5 U/mL). Thereafter, arterial contractions in response to cumulative additions of serotonin were recorded. Arterial contractions were expressed as a percentage of maximal potassium chloride-induced contractions. Arterial sensitivity was expressed as the EC50, the concentration of serotonin that produced a half-maximal contraction. Exposure of aortic rings to thrombin alone produced contractions of 11% and 22% for rings with and without endothelium, respectively. Removal of the endothelium had no effect on maximal serotonin-induced contractions (93% with endothelium vs 98% without). In contrast, maximal serotonin-induced contractile force was increased after pretreatment with thrombin (107% vs 121% for rings with and without endothelium, respectively; P less than .01). Arterial sensitivity to serotonin was not affected by the removal of endothelium. However, thrombin pretreatment increased (P less than .01) arterial sensitivity to serotonin 2.6-fold and 4.7-fold for rings with and without endothelium, respectively. The results of this study demonstrate that arterial contractions due to serotonin are amplified by thrombin and suggest that vasospasm may be more likely to occur at sites in arteries where the endothelium is absent and both thrombin and serotonin are present.

Abnormal fatty acid profile in chronic hemodialysis patients: possible deficiency of essential fatty acids.

Plasma fatty acid profiles from maintenance hemodialysis patients (n = 9) were compared with those from healthy volunteers (n = 9). Hemodialysis patients had significantly higher levels of oleic acid, 15.3 +/- 1.1 vs. 8.9 +/- 0.6% (p less than 0.0001), and lower levels of arachidonic acid (6.0 +/- 0.5 vs. 8.4 +/- 0.3%, p less than 0.0009). Linolenic and linoleic acids, the essential fatty acid and precursors of arachidonic acid, were also significantly lower than normal in the dialysis group. These data show that dialysis patients have fatty acid abnormalities suggesting relative depletion of essential fatty acids. These observations are important because these abnormalities may play an important role in the pathogenesis of some common clinical conditions associated with uremia, such as a constellation of skin problems, fragility of erythrocytes, lipid anomalies and hormonal aberrations.

Central nervous system effects of lactate infusion in primates.

The concentration of total lactate in cisternal fluid increased threefold, from 12.3 +/- 2.1 to 37.6 +/- 8.9 mg/dl, during a 20-min intravenous infusion of 1 M racemic sodium lactate (10 mEq/kg) in 3 anesthetized, mechanically ventilated baboons. Rises in cisternal lactate lagged behind arterial lactate increases, but occurred during the time interval in which susceptible humans typically panic in response to lactate infusion. Subsequent to cisternal lactate increases, cisternal pH and HCO3- concentration progressively increased during a 105-min interval following lactate infusion. No consistent changes in cisternal pCO2 occurred during or subsequent to lactate infusion. These preliminary findings fail to support the hypothesis that lactate-induced panic is mediated by increasing central nervous system pCO2. Instead, these data demonstrate that lactate can rapidly increase in the central nervous system during lactate infusion, suggesting new lines of investigation for studying the mechanisms responsible for lactate-induced panic.

Fatty acid abnormalities in hemodialysis patients: effect of L-carnitine administration.

Serum fatty acid profiles were determined using gas chromatography/mass spectrometry in three groups of subjects. Compared to normal controls, eight patients on maintenance hemodialysis had significantly lower proportions of linoleic (28.15 +/- 1.3 vs. 26.5 +/- 1.4%, P less than 0.003), linolenic (0.49 +/- 0.2 vs. 0.21 +/- 0.2%, P less than 0.04) and arachidonic acids (8.42 +/- 0.9 vs. 6.0 +/- 1.5%, P less than 0.0001). Dialysis patients also had higher proportions of oleic (8.9 +/- 1.8 vs. 15.3 +/- 3.5%, P less than 0.0001) and n-9 eicosatrienoic acids (0.26 +/- 0.2 vs. 0.54 +/- 0.3%, P less than 0.04). Ratios between oleic and arachidonic acid and between eicosatrienoic and arachidonic acids were also significantly higher in the dialysis group. In a separate group of either chronic dialysis patients, L-carnitine was given intravenously for a period of 6 to 18 months. In this group linoleic, linolenic and eicosatrienoic acids were not significantly different from normal controls. The ratio between eicosatrienoic and arachidonic acids was also similar to normal controls. However, arachidonic acid remained significantly lower and oleic acid significantly elevated in the carnitine group. The ratio of saturated to unsaturated fatty acid was higher in the untreated dialysis patients compared to L-carnitine treated patients (0.75 +/- 0.07 vs. 0.65 +/- 0.06, P less than 0.01). Significant abnormalities in distribution of fatty acids was seen in hemodialyzed patients. Thus preliminary data suggest significant depletion of essential fatty acids in dialysis patients which is partially corrected by treatment of patients with L-carnitine.

Influence of hypothermic cardiopulmonary bypass on atrial natriuretic factor levels.

Atrial natriuretic factor (ANF) is a peptide released from the heart in response to atrial distension. This peptide causes diuresis, vasodilatation, decreased blood pressure, and antagonizes the renin-aldosterone and antidiuretic hormone neuraxes. The influence of cardiopulmonary bypass and cardiac surgery on the circulation and release of ANF is unknown. Plasma ANF concentrations were therefore determined in patients undergoing coronary artery revascularization (CABG) and mitral valve replacement (MVR). Peptide levels were unchanged following anaesthetic induction. Plasma ANF concentrations decreased significantly during hypothermic (less than or equal to 28 degrees C) cardiopulmonary bypass in both patient groups. After 60 minutes of cardiac bypass, ANF declined from (mean +/- SEM) 512 +/- 132 to 20 +/- 6 pg.ml-1 (P less than 0.05) during MVR, and from 178 +/- 41 to 110 +/- 48 pg.ml-1 during CABG (P less than 0.05). Rewarming during bypass was associated with an increase in ANF concentration in both groups. Heparin anticoagulation and protamine reversal had no effect on immunoreactive ANF levels. In patients undergoing CABG, there was a linear relationship between plasma ANF concentration (pg.ml-1) and right atrial pressure (mmHg) prior to cardiopulmonary bypass (r = 0.86, P less than 0.005). However, one and three hours after cardiopulmonary bypass there was no significant relationship between right atrial pressure and ANF plasma levels. These results suggest that reduction in plasma ANF concentration occurs during hypothermic cardiopulmonary bypass. Furthermore, the proportional relationship between atrial distension and circulating ANF concentration was altered following cardiac surgery.

Evaluation of a blood gas and chemistry monitor for use during surgery.

An observational study was performed to evaluate a new blood gas and chemistry monitor (GEM-6 Diamond Sensor Systems, Ann Arbor, Michigan) in nine patients during cardiac surgery. Paired blood samples were analyzed by the instrument under test and by standard clinical laboratory instruments. The differences between the measurements of the new and the standard instruments are summarized as follows (mean +/- standard deviation, units of measure, number of samples): pH (-0.039 +/- 0.02, 154); PCO2 (2.63 +/- 1.8 mmHg, 154); venous PO2 (-2.0 +/- 3.0 mmHg, 72), hematocrit (4.7 +/- 2.7%, 98), potassium (0.18 +/- 0.13 mmol, 100), and ionized calcium (0.195 +/- 0.11 mmol, 100). Because the differences in arterial PO2 measurements were markedly heteroscedastic, a logarithmic transformation was employed, which upon retransformation gave the test instrument's 95% confidence limits as within 5.1% below to 46% above the nominal value on 82 samples. However, on the 14 samples having nominal values below 165 mmHg (the upper limit of the calibrated range of the GEM-6) the 95% confidence limits were from 5.4% below to 23.6% above the nominal reading. No failures of the test instrument occurred during the evaluation, and quality control standards run before, midway through, and again after sampling from each patient all gave readings within the manufacturer's tolerance. For all variables except hematocrit and ionized calcium, this instrument matches the values from the laboratory well enough over the clinically important range to supplant it for intraoperative monitoring purposes.