Increased Anxiety in Partners of Patients with a Cardioverter-Defibrillator: The Role of Indication for ICD Therapy, Shocks, and Personality

Background: The partner of the implantable cardioverter‐defibrillator (ICD) patient serves as an important source of support for the patient, which may be hampered if the partner experiences increased distress. We examined (1) potential differences in anxiety and depressive symptoms in ICD patients compared to their partners, and (2) the extent to which the partner's personality is a more important determinant of partner distress than patient clinical characteristics, using a prospective design. Methods: Consecutively implanted ICD patients (n = 196) and their partners (n = 196) completed a set of psychological questionnaires at baseline and 6 months after implantation. Results: Analysis of variance with repeated measures showed that partners had significantly higher levels of anxiety compared to patients (F(1,390) = 16.431; P < 0.001) but not depressive symptoms (F(1,390) = 0.186; P = 0.67). There was a significant overall reduction in anxiety (F(1,390) = 79.552; P < 0.001) and depressive symptoms (F(1,390) = 39.868; P < 0.001) over 6 months, with group (i.e., patient vs partner) exerting a stable effect on anxiety (F(1,390) = 0.966; P = 0.33) and depressive symptoms (F(1,390) = 0.025; P = 0.87). These results remained in adjusted analysis. Determinants of anxiety and depressive symptoms in partners included secondary prophylaxis in patients (Ps < 0.001–0.002), Type D personality of the partner (Ps < 0.001–0.001), secondary prophylaxis by shock interaction (P = 0.002; anxiety only), and secondary prophylaxis by Type D interaction (Ps = 0.001–0.003). Conclusions: Partners had higher levels of anxiety but not depression than ICD patients. Partner distress could be attributed not only to the partner's personality, but also to patient clinical characteristics, primarily secondary prophylaxis for ICD therapy. These results indicate that information on the clinical characteristics of the patient in addition to partner characteristics may help identify partners at risk of distress.     

Which platelet function test is suitable to monitor clopidogrel responsiveness? A pharmacokinetic analysis on the active metabolite of clopidogrel

Summary. Background: Multiple platelet function tests claim to be P2Y12‐pathway specific and capable of capturing the biological activity of clopidogrel. Objectives: The aim of the present study was to determine which platelet function test provides the best reflection of the in vivo plasma levels of the active metabolite of clopidogrel (AMC). Patients/methods: Clopidogrel‐naive patients scheduled for elective percutaneous coronary intervention (PCI) received a 600 mg loading dose of clopidogrel and 100 mg of aspirin. For pharmacokinetic analysis, blood was drawn at 0, 20, 40, 60, 90, 120, 180, 240 and 360 min after clopidogrel loading and peak plasma concentrations (C_max) of the AMC were quantified with liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). Platelet function testing was performed at baseline and 360 min after the clopidogrel loading. Results: The VASP‐assay, the VerifyNow P2Y12‐assay and 20 μmol L^?1 adenosine diphosphate (ADP)‐induced light transmittance aggregometry (LTA) showed strong correlations with C_max of the AMC (VASP: R² = 0.56, P < 0.001; VerifyNow platelet reactivity units (PRU): R² = 0.48, P < 0.001; VerifyNow %inhibition: R² = 0.59, P < 0.001; 20 μmol L^?1 ADP‐induced LTA: R² = 0.47, P < 0.001). Agreement with C_max of the AMC was less evident for 5 μmol L^?1 ADP‐induced LTA or whole blood aggregometry (WBA), whereas the IMPACT‐R ADP test did not show any correlation with plasmalevels of the AMC. Conclusion: The flow cytometric VASP‐assay, the VerifyNow P2Y12 assay and, although to a lesser extent, 20 μmol L^?1 ADP‐induced LTA correlate best with the maximal plasma level of the AMC, suggesting these may be the preferred platelet function tests for monitoring the responsiveness to clopidogrel.     

High on‐aspirin platelet reactivity as measured with aggregation‐based,cyclooxygenase‐1 inhibition sensitive platelet function tests is associated with the occurrence of atherothrombotic events

Summary. Background: High on‐aspirin platelet reactivity (HAPR) is associated with atherothrombotic events following percutaneous coronary intervention (PCI). The aim of the present study was to identify the platelet function test sensitive for platelet cyclooxygenase‐1 inhibition that best predicts atherothrombotic events. Methods and results: Nine hundred and fifty‐one consecutive patients on dual antiplatelet therapy undergoing elective PCI were enrolled. On‐aspirin platelet reactivity was measured in parallel by arachidonic acid (AA)‐induced light transmittance aggregometry (AA‐induced LTA), the VerifyNow® Aspirin Assay (VerifyNow® Aspirin Assay), the arachidonic acid prestimulated IMPACT‐R (IMPACT‐R AA) and the PFA‐100 collagen/epinephrine cartridge (PFA COL/EPI). Cut‐offs for HAPR were established by receiver‐operator characteristic curve analysis. At 1‐year follow‐up, the composite of all‐cause death, non‐fatal acute myocardial infarction, stent thrombosis and ischemic stroke occurred more frequently in patients with HAPR when assessed by LTA [10.1% vs. 6.0%, P = 0.020 (n = 925)] and VerifyNow^® [13.3% vs. 5.9%, P = 0.015 (n = 422)]. The VerifyNow^® ASA assay (AUC = 0.78) and, to a lesser extent, AA‐induced LTA (AUC = 0.73) added significantly to a model consisting of clinical and procedural risk factors in predicting atherothrombotic events. In contrast, the IMPACT‐R (n = 791) and the PFA Collagen/Epinephrine (n = 719) were unable to discriminate between patients with and without primary endpoint at 1‐year follow‐up. None of the platelet function tests was able to identify patients at risk for bleeding. Conclusions: AA‐induced LTA and the VerifyNow^® ASA test were able to identify aspirin‐treated patients undergoing PCI with stenting at risk for atherothrombotic events. The VerifyNow^® Aspirin Assay had the highest predictive accuracy. None of the tests was able to identify patients at higher risk of bleeding.     

Purification of Human Interferon by Antibody Affinity Chromatography, using Highly Absorbed Anti-interferon

Antibodies against partially purified human leucocyte interferon (PIF) were bound to Sepharose 4B and crude interferons applied on this affinity column were purified, up to 8 × 10⁵ interferon units (IFU) per mg protein in one step. Antibodies against PIF were absorbed with immobilized crude human leucocyte interferon bound to Sepharose, whereby antibodies against impurities were predominantly removed. Extensively absorbed antisera were coupled to Sepharose and used for antibody affinity chromatography of crude interferon preparations. Leucocyte and fibroblast interferons were purified in one step with around 100% recovery, up to 1 × 10⁸ IFU per mg protein, and Namalva interferon up to 2 × 10⁷ IFU/mg. SDS electrophoresis of affinity-purified leucocyte interferon revealed that the interferon activity appeared in two bands (19,000 and 23,000 D).     

Disposition and Elimination of Three Polychlorinated Dibenzofurans in the Liver of the Rat

Disposition and Elimination of Three Polychlorinated Dibenzofuransin the Liver of the Rat. VAN DEN BERG, M., DE JONGH, J., ECKHART,P., AND VAN DER WIELEN, F. W. M. (1989). Fundam. Appl. Toxicol.12, 738–747. The disposition and elimination of 1,2,3,6,7,8-HxCDF(HxCDF), 1,2,3,7,8-PnCDF (1-PnCDF), and 2,3,4,7,8-PnCDF (4-PnCDF)were studied in liver of female Sprague-Dawley rats after administrationof a single oral dose of 3.5–6.3 µg/kg. The dispositionof these PCDF congeners was structure and vehicle dependent.Administration in peanut oil caused the highest liver retention,compared with administration through the standard diet. Half-livesin liver for 1-PnCDF, 4-PnCDF, and HxCDF were 3.3, 108, and73 days, respectively. 4-PnCDF showed very high liver retention:70% of the dose in the first days after administration. To studykinetic interaction in the liver, mixtures of 1-PnCDF and 4-PnCDF(Experiment I) and of 4-PnCDF and HxCDF (Experiment II) wereadministered. The presence of 4-PnCDF in Experiment I did notsignificantly influence the half-life of I-PnCDF. In ExperimentII the estimated half-life of 4-PnCDF was again 108 days, butfor HxCDF an increased half-life was found, 156 days. It isconcluded that PCDFs with a chlorine substituent(s) adjacentto the oxygen bridge (4- and 6-positions) are eliminated vcryslowly with 14 much greater than that of TCDD.     

Contradictory effects of dopamine at 32°C in pigs anesthetized with ketamine

Background: In critically ill patients who were surface cooled to 332C, we have observed that dopamine sometimes causes a substantial decrease in blood pressure. The present study was designed to compare the effects of dopamine in normothermia to those seen after surface cooling to 32C.
Methods: Seven pigs with a mean body weight of 21 kg were anesthetized with ketamine and muscle relaxation was induced with pancuronium. They were mechanically ventilated and given dopamine infusions (5 and 12 μg · kg^-1 min^-1) in normothermia and after surface cooling by cold water immersion to a central blood temperature of 320C (range 31.6–32.6C).
Results: In normothermia, dopamine at a dose of 5 μg · kg^-1 min^-1 increased mean arterial blood pressure (MAP) by 16% ( P < 0.01) and cardiac output (CO) by 9% ( P =0.051); at 12 μg kg^-1 min^-1 dopamine increased MAP by 26% ( P < 0.01) and CO by 18% ( P < 0.01). In hypothermia, MAP and CO did not change at an administration rate of 5 μg kg^-l · min^-1; at 12 μg · kg^-1 min^-1 CO was unchanged but MAP was significantly reduced by 15% ( P < 0.01).
Conclusion: Dopamine increased CO and MAP in normothermia but not at 32C, where there was even a significant reduction of MAP in this porcine model.     

Effects of buffering in hypercapnia and hypercapnic hypoxemia

Anesthetized, paralyzed and mechanically ventilated pigs were exposed to extreme hypercapnia (Paco_2-20 kPa) at Fio₂ 0.4 for 480 min, with (n = 6) or without (n = 6) continuous infusion of isotonic buffers (bicarbonate and trometamol). Arterial pH was higher in buffered animals than controls, 7.21 ±0.01 vs 7.01±0.01 (mean ± s.e.mean, P < 0.01). Serum osmolality and Paco₂ did not differ between groups throughout the experiment. The hemodynamic response to hypercapnia was attenuated in the buffered group, who had lower heart rate, 133 ± 6 vs 189±12 min^-1 (P < 0.01), mean arterial pressure (MAP) 109 ± 4 vs 124 ± 4 mmHg (14.5 ± 0.5 vs 16.5 ± 0.5 kPa) (P < 0.05), mean pulmonary arterial pressure 16±1 vs 23 ± 1 mmHg (2.1 ±0.1 vs 3.1 ±0.1 kPa) (P < 0.01), and pulmonary vascular resistance (PVR) 249 ± 21 vs 343 ± 20 dyn s-cm^-5 (2490±210 vs 3430±200 μN-s-cm^-5) (P < 0.01), compared with the control group. Subsequently, both groups were exposed to hypercapnic hypoxemia by stepwise increases in Fio₂ (0.15, 0.10, 0.05) at 30-min intervals, while Fico₂ was kept at 0.2. PVR increased in both groups (P < 0.05) but, except for heart rate, all hemodynamic differences between the groups disappeared during hypoxia. At Fio₂ 0.15, buffered animals had higher arterial oxygen saturation (73 ± 5%) than the controls (55 ± 5%), (P < 0.05). The control animals died after 1–29 min (mean 14 min) at Fio₂ 0.10, while all buffered animals survived Fio₂ 0.10 with stable MAP (122 ± 14 mmHg (16.3 ± 1.9 kPa). The buffered animals died after 4–22 min (mean 15 min) at Fio₂ 0.05. We conclude that buffering to a pH of 7.21 attenuates the observed hemodynamic response in extreme hypercapnia and improves survival in hypercapnic hypoxemia.     

Induction of Cytochrome P450 Isoenzymes after Toxicokinetic Interactions between 2,3,7,8-Tetrachlorodibenzo-p-dioxin and 2,2',4,4',5,5'-Hexachlorobiphenyl in the Liver of the Mouse

One group of male C57BL/6J mice received a single oral doseof 1 nmol 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)/kg. Sixother groups received single oral doses of 100, 300, or 1000µmol2,2',4,4',5,5'-hexachlorobiphenyl (HxCB)/kg, alone or in combinationwith 1 nmol/kg TCDD. Liver deposition of both compounds wasstudied at Day 3 after dosage. Hepatic CYP1A1 and CYP1A2 proteinlevels and related 7-ethoxyres-orufin-O-deethylation (EROD)and acetanilide 4-hydroxylation (ACOH) activities were alsostudied. A significant increase in the hepatic deposition ofTCDD was observed in all three mixed dose groups but TCDD didnot influence hepatic HxCB deposition. TCDD did increase bothCYP1A1 and CYP1A2 protein levels. In the HxCB-treated groups,CYP1A2 levels were also increased in a dose-dependent way butCYP1A1 levels were not increased. CYP1A2 activities (ACOH),but not protein levels, in the TCDD groups cotreated with HxCBwere higher than those in the group treated with TCDD alone.CYP1A1-dependent EROD activity and CYPlA2-dependent ACOH activitywere induced in all treated dose groups. It is concluded thatthe present results do not confirm a direct role of CYP1A2 inductionin the increase of hepatic TCDD levels by HxCB cotreatment inthe mixed HxCB/TCDD dose groups. However, in this aspect, thediscrepancy between CYP1A2 activities and protein levels remainsto be explained.     

Vomiting after ophthalmic surgery

The usefulness of intra-operative antiemetics and postoperative oral fluid restriction in the prevention of vomiting following anaesthesia for ophthalmic surgery, was studied in 200 patients. They were allocated into four groups of 50 and given either saline (as control), droperidol, metoclopramide or prochlorperazine. Oral intake was restricted postoperatively in half of the patients of each group. Anaesthesia comprised morphine and atropine premedication and a halothane, nitrous oxide and oxygen spontaneous breathing technique. No significant beneficial effects resulted from intra-operative antiemetics; vomiting incidences of 26% after saline and droperidol, 28% after metoclopramide and 14% after prochlorperazine were observed. Younger patients and females vomited most frequently. Restriction of oral fluids did not decrease the incidence of vomiting but demonstrated that approximately half of those patients who vomit do so with their first postoperative oral intake. Vomiting was observed more frequently after non intra-ocular surgery than after intra-ocular surgery (37% cf. 16%, p less than 0.01) and postoperative analgesics were required by more non intra-ocular patients than by intra-ocular patients (25% cf. 5%, p less than 0.001). Squint patients vomited most frequently (48%) and most frequently required postoperative analgesia (35%).